Dictionary of Microbiology & Molecular Biology [3rd Edition, Revised] 0470035455, 9780470035450

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Dictionary of Microbiology and Molecular Biology, Third Edition Paul Singleton and Diana Sainsbury © 2006 John Wiley & Sons Ltd. ISBN: 0-470-03545-5

We would like to dedicate this book to the memory of Hubert Sainsbury. His lively and enquiring mind and his passion for knowledge and understanding were always an inspiration, and his enthusiasm for this Dictionary was a strong motivating force during its long gestation. The book owes more to him than he would have believed.

Copyright  1978, 1987, 2001, 2006

John Wiley & Sons Ltd., The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, England Telephone (+44) 1243 779777

Email (for orders and customer service enquiries): [email protected] Visit our Home Page on www.wileyeurope.com or www.wiley.com 1st edition 1978 (reprinted 1980) 2nd edition 1987 (reprinted 1988, 1989, 1991, 1994) Paperback edition 1993 (reprinted 1993, 1994, 1995, 1996 (twice), 1997 (twice), 1999, 2000) 3rd edition 2001 (reprinted 2002) 3rd edition revised 2006 Japanese edition (Asakura, Tokyo) 1997 Chinese edition in preparation 2006 All Rights Reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning or otherwise, except under the terms of the Copyright, Designs and Patents Act 1988 or under the terms of a licence issued by the Copyright Licensing Agency Ltd, 90 Tottenham Court Road, London W1T 4LP, UK, without the permission in writing of the Publisher. Requests to the Publisher should be addressed to the Permissions Department, John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, England, or emailed to [email protected], or faxed to (+44) 1243 770620. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the Publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought. Other Wiley Editorial Offices John Wiley & Sons Inc., 111 River Street, Hoboken, NJ 07030, USA Jossey-Bass, 989 Market Street, San Francisco, CA 94103-1741, USA Wiley-VCH Verlag GmbH, Boschstr. 12, D-69469 Weinheim, Germany John Wiley & Sons Australia Ltd, 42 McDougall Street, Milton, Queensland 4064, Australia John Wiley & Sons (Asia) Pte Ltd, 2 Clementi Loop #02-01, Jin Xing Distripark, Singapore 129809 John Wiley & Sons Canada Ltd, 6045 Freemont Blvd, Mississauga, ONT, L5R 4J3, Canada Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.

Library of Congress Cataloging-in-Publication Data Requested British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library ISBN-13 978-0-470-03545-0 (PB) ISBN-10 0-470-03545-5 (PB) Typeset in 10/12pt Times by Laserwords Private Limited, Chennai, India Printed and bound in Great Britain by Antony Rowe Ltd, Chippenham, Wiltshire, UK This book is printed on acid-free paper responsibly manufactured from sustainable forestry, in which at least two trees are planted for each one used for paper production.

Preface This edition follows the style of previous editions. It has similar aims, and was written with the same enthusiasm and care. It is vital that readers be aware of the type of alphabetization used in the Dictionary. A glance at ‘Notes for the User’ – particularly the first paragraph – is essential. September 2001

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Preface to the Second Edition In writing this new edition of the Dictionary we had several aims in mind. One of these was to provide clear and up-to-date definitions of the numerous terms and phrases which form the currency of communication in modern microbiology and molecular biology. In recent years the rapid advances in these disciplines have thrown up a plethora of new terms and designations which, although widely used in the literature, are seldom defined outside the book or paper in which they first appeared; moreover, ongoing advances in knowledge have frequently demanded changes in the definitions of older terms – a fact which is not always appreciated and which can therefore lead to misunderstanding. Accordingly, we have endeavoured to define all of these terms in a way which reflects their actual usage in current journals and texts, and have also given (where appropriate) former meanings, alternative meanings, and synonyms. A second – but no less important – aim was to encapsulate and integrate, in a single volume, a body of knowledge covering the many and varied aspects of microbiology. Such a reference work would seem to be particularly useful in these days of increasing specialization in which the reader of a paper or review is often expected to have prior knowledge of both the terminology and the overall biological context of a given topic. It was with this in mind that we aimed to assemble a detailed, comprehensive and interlinked body of information ranging from the classical descriptive aspects of microbiology to current developments in related areas of bioenergetics, biochemistry and molecular biology. By using extensive cross-referencing we have been able to indicate many of the natural links which exist between different aspects of a particular topic, and between the diverse parts of the whole subject area of microbiology and molecular biology; hence the reader can extend his knowledge of a given topic in any of various directions by following up relevant cross-references, and in the same way he can come to see the topic in its broader contexts. The dictionary format is ideal for this purpose, offering a flexible, ‘modular’ approach to building up knowledge and updating specific areas of interest. There are other more obvious advantages in a reference work with such a wide coverage. Microbiological data are currently disseminated among numerous books and journals, so that it can be difficult for a reader to know where to turn for information on a term or topic which is completely unfamiliar to him. As a simple example, the name of an unfamiliar genus, if mentioned out of context, might refer to a bacterium, a fungus, an alga or a protozoon, and many books on each of these groups of organisms may have to be consulted merely to establish its identity; the problem can be even more acute if the meaning of an unfamiliar term is required. A reader may therefore be saved many hours of frustrating literature-searching by a single volume to which he can turn for information on any aspect of microbiology. An important new feature of this edition is the inclusion of a large number of references to recent papers, reviews and monographs in microbiology and allied subjects. Some of these references fulfil the conventional role of indicating sources of information, but many of them are intended to permit access to more detailed information on particular or general aspects of a topic – often in mainstream journals, but sometimes in publications to which the average microbiologist may seldom refer. Furthermore, most of the references cited are themselves good sources of references through which the reader can establish the background of, and follow developments in, a given area. While writing this book we were very fortunate in having exceptional and invaluable cooperation from a number of libraries in South-West England. In particular, we would like to acknowledge the generous help of Mr B. P. Jones, B.A., F.L.A., of the Medical Library, University of Bristol, Mrs Jean Mitchell of the Library at Bicton College of Agriculture, Devon, and Maureen Hammett of Exeter Central Library, Devon. Finally,

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Preface to the Second Edition

we are grateful to Michael Dixon, Patricia Sharp, and Prue Theaker at John Wiley & Sons, Chichester, for their enthusiastic and efficient cooperation in the production of the book. Paul Singleton & Diana Sainsbury Clyst St Mary, Devon, April 1987

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Notes for the User 1. Alphabetization. Alphabetization would need no comment if every term consisted of a single word; in practice, however, many terms consist of two or more words and often contain single letters, numbers, symbols etc. Terms consisting of two or more words can be alphabetized in either of two ways: on the basis of the first word, or on the basis that both or all of the words are run together and treated as one; thus, e.g., according to the ‘first-word’ (‘nothing-before-something’) system, red tide comes before redox potential, but according to the second system redox potential comes before red tide. Terms in this Dictionary have been alphabetized by the first-word system; in this system a single letter counts as a word (hence e.g. R plasmid comes before rabies), as does a group of letters (e.g. an abbreviation, or a gene designation). Examples: air sacculitis airlift fermenter AIV process Ajellomyces

atoxyl ATP ATP synthase ATPase

black stem rust black wart disease black yeasts blackeye cowpea mosaic virus

RecA protein recapitulation theory recB gene RecBC pathway

When a hyphen connects two complete words, or occurs between a letter (or group of letters) and a word, the hyphen is regarded as a space; however, if a hyphen is used to link a prefix to a word (i.e., if the letters preceding the hyphen form a part-word which cannot stand alone) the term is alphabetized as though it were a single, non-hyphenated word. (In a few cases an entry heading contains words which can be written as separate, hyphenated or non-hyphenated words, or closed up as a single word: e.g. red water fever, red-water fever, redwater fever; in such cases an entry or cross-reference has been included in both possible positions.) Examples: BL-type starter bla gene black beans Black beetle virus

M M antigen M-associated protein M bands

nonsense mutation nonsense suppressor non-specific immunity non-specific immunization

preaxostyle pre-B cell prebuccal area precipitation

When a Greek letter forms a significant part of an entry heading it is counted as a word and is alphabetized as spelt (i.e., a as alpha, b as beta, etc: see Appendix VI for the Greek alphabet). A Greek letter is ignored for the purposes of alphabetization if it is a relatively minor qualification: e.g., part of a chemical designation (which can usually be replaced by a number, as in b-hydroxybutyrate, = 3-hydroxybutyrate). Examples: Delhi boil 1 delta agent d antigen

MTOC µ

Mu mu chain

pHisoHex fX phage group Phlebia Phlebotomus

polyhedrosis poly-b-hydroxyalkanoate poly-b-hydroxybutyrate Polyhymenophorea

A number which forms part of an entry heading affects the position of that entry only if the number immediately follows a letter or word (but cf. chemical names, below). A number which precedes a letter or word is usually ignored, although in the few cases where a number is the first and main part of an entry heading it is alphabetized as spelt. Letter–number combinations come after a letter–space but before letter–letter combinations, as in the illustrative sequence A, A2, A2A, A3, A22, AA, ABA etc. Roman numerals are treated as ordinary numbers (I as 1, II as 2 etc). (The reader should bear in mind that, in an unfamiliar term, ‘I’ could be a letter I or a Roman one, and its location in the Dictionary will be affected accordingly; similarly, ‘V’ could be letter V or Roman five. O and 0 (zero) may also be confused. If in doubt check both possible positions.) Examples: bacteriophage bacteriophage bacteriophage bacteriophage

Pf2 fI fII f6

D loop D period 12D process D-type particles

Fitz-Hugh–Curtis syndrome five–five–five test five-kingdom classification five–three–two symmetry ix

T1 side-chains T-2 toxin T2H test T7 phage group

Notes for the User

Subscript/superscript numbers and letters are alphabetized as though they were ordinary numbers and letters (except in the case of ion designations: see below). Examples: avoparcin aw axenic axial fibrils

B virus B12 coenzymes B663 Babes–Ernst granules

C3 convertase C3 cycle C3bina C5 convertase

CO2 CO2 -stat CoA coactin

Primes, apostrophes and other non-alphabetizable symbols (including e.g. plus, minus and % signs) are ignored. Examples: brown rust Browne’s tubes Brownian movement Brown’s tubes

F antigens F+ donor F-duction F factor

Gautieriales Gazdar murine sarcoma virus GC% GC type

pluronic polyol F127 plus progamone plus strand Pluteaceae

In chemical names qualifications such as D-, L-, N -, o-, p-, numbers and Greek letters, as well as hyphens between parts of chemical names, are all ignored for the purposes of alphabetization. Examples: acetyl-CoA synthetase N-acetyl-D-glucosamine acetylmethylcarbinol N-acetylmuramic acid

diazomycin A 6-diazo-5-oxo-L-norleucine diazotroph dibromoaplysiatoxin

methylmethane sulphonate N-methyl-N′ -nitro-N-nitrosoguanidine N-methyl-N-nitrosourea Methylobacterium

In entry headings which include an ion designation, the ion is treated as a word, the charge being ignored; thus, H+ is regarded as H, Ca2+ as Ca, etc. Examples: H antigens H+ -ATPase H+ /2e− ratio H-lysin

H+ /P ratio H+ -PPase H strand H-1 virus

K cells K+ pump K+ transport K virus

Na+ -ATPase Na+ -motive force Na+ pump nabam

2. Cross-references. References from one entry to another within the Dictionary are indicated by SMALL CAPITAL letters. In order to effect maximum economy of space, information given in any particular entry is seldom repeated elsewhere, and cross-referencing has been extensively employed to ensure continuity of information. In some cases a complete understanding of an entry, or an appreciation of context, is dependent on a knowledge of information given in other entries; where it is particularly important to follow up a crossreference, the cross-reference is followed by ‘q.v.’. In other cases a cross-reference may be used to link one topic with another of related interest, or to extend the scope of a given topic in one or more directions; in such cases a cross-reference is usually preceded by ‘see also’ or ‘cf.’. (N.B. For a variety of reasons, not every microbiological term or taxon used in the text is cross-referred – even though most of these terms and taxa are defined in the Dictionary; the reader is therefore urged to use the Dictionary for any unfamiliar term or taxon.) When reading an entry for a genus, family or other taxon, it is especially important to follow up, when indicated, a cross-reference to the higher taxon to which it belongs. An entry for a given higher taxon gives the essential features applicable to all members of that taxon, and such features are usually not repeated in the entries for each of the constituent lower-ranked taxa; thus, in failing to follow up such cross-references, the reader will forfeit fundamental information relating to the lower taxon in question. In some cases an entry heading is followed simply by ‘See CROSS-REFERENCE’. This is not intended to indicate that the two terms are synonymous (usually they are not); such referral signifies only that the meaning of the term is given under the heading indicated. When the entry heading and cross-reference are synonymous, this is indicated by Syn., thus: entry heading Syn. CROSS-REFERENCE. 3. External references. References to papers, articles etc in books or journals are given in square brackets. In order to save space, books are referred to by a ‘Book ref.’ number, and journal titles are abbreviated x

Notes for the User

somewhat more than is usual; keys to book reference numbers and journal title abbreviations can be found at the end of the Dictionary (after the Appendices). A book reference is usually quoted as a source of general background information for the reader, while papers in journals are usually quoted for specific details of current information (or for reviews) and/or for their references to other literature in the field. We should emphasize that the papers we have cited are not necessarily (and are commonly not) those which were the first to report a particular fact, finding or theory; rather, we have chosen, where possible, to cite the most recent references available to us, so that the reader is referred to current information and can, if he wishes, trace the earlier literature via references given in the cited papers. We should also point out that the quoting of a single reference in an entry is not intended to indicate that the entry was written solely from information in that paper or book. In relatively few cases does the information in an entry derive from a single source; in the great majority of entries the information has been derived from, or checked against, a range of sources, but limitations of space have necessarily prevented us from citing all of them. 4. Numbered definitions. In some cases a term is used with different meanings by different authors, or it may have different meanings in different contexts; for such a term the various definitions are indicated by (1), (2), (3), etc. The order in which the numbered definitions occur is not intended to reflect in any way appropriateness or frequency of usage. 5. Taxonomy. See entries ALGAE, BACTERIA, FUNGI, PROTOZOA and VIRUS for some general comments on the taxonomy of each of these groups of microorganisms. Each of these entries (except that on bacteria) provides a starting point from which the reader can, via cross-references, follow through a hierarchical system down to the level of genus and, in many cases, species and below; similarly, the hierarchy can be ascended from genus upwards. 6. The Greek alphabet. See Appendix VI.

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Dictionary of Microbiology and Molecular Biology, Third Edition Paul Singleton and Diana Sainsbury © 2006 John Wiley & Sons Ltd. ISBN: 0-470-03545-5

A A

AB-transhydrogenase See TRANSHYDROGENASE. ABA ABSCISIC ACID. abacavir A NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR. abacterial pyuria See PYURIA. Abbe condenser A simple two- or three-lens substage CONDENSER which is uncorrected for spherical or chromatic aberrations. ABC (1) (immunol.) ANTIGEN-BINDING CELL. (2) See ABC TRANSPORTER. ABC excinuclease See EXCISION REPAIR. ABC exporter An ABC TRANSPORTER concerned with export/ secretion. These systems are found in both prokaryotic and eukaryotic microorganisms and in higher animals, including man. (The mammalian transporters include P-glycoprotein (‘multidrug-resistance protein’) – a molecular pump by which some types of cancer cell can extrude anti-cancer drugs.) In Saccharomyces cerevisiae, an ABC exporter mediates secretion of a peptide PHEROMONE (the a-factor) which regulates sexual interaction. In bacteria, ABC exporters transport various proteins (including enzymes and antibiotics) and, in some species, the polysaccharide components of the capsule; an exporter may be able to transport various related or similar molecules. [Bacterial ABC exporters: MR (1993) 57 995–1017.] In Escherichia coli the a-haemolysin is secreted via an ABC exporter – a one-step process direct from cytoplasm to environment; this exporter is in the type I class of protein secretory systems in Gram-negative bacteria (see PROTEIN SECRETION). Other proteins secreted by these systems include the cyclolysin of Bordetella pertussis and the alkaline protease of Pseudomonas aeruginosa. In Streptomyces antibioticus an ABC exporter secretes the antibiotic OLEANDOMYCIN. Bacterial proteins secreted by ABC exporters typically lack an N-terminal signal sequence (see SIGNAL HYPOTHESIS) but they have a C-terminal secretion sequence that may interact directly with the ABC protein. Exporters which transport molecules to the periplasm, or outer membrane, as the final destination may have fewer protein components than those exporters which secrete proteins. In Gram-negative bacteria, at least some exporters appear to consist of (i) ABC proteins; (ii) a membrane fusion protein (MFP) (in the periplasm and cytoplasmic membrane); and (iii) an OUTER MEMBRANE component. Assembly seems to occur in a definite sequence which is promoted and/or initiated by the binding of substrate (i.e. the molecule to be secreted) to the ABC protein; in this scheme, substrate–ABC binding is followed by ABC–MFP interaction – MFP then binding to the outer membrane, presumably to complete the secretory channel [EMBO (1996) 15 5804–5811]. ABC immunoperoxidase method An IMMUNOPEROXIDASE METHOD involving the use of a preformed avidin–biotin–peroxidase complex (ABC) which has surplus biotin-binding capacity. Initially, a (‘primary’) antiserum is raised against the required antigen; if the primary antiserum is derived from e.g. a rat, a ‘secondary’ anti-rat antiserum is prepared, and the anti-rat Ig antibodies are BIOTINylated. To locate a specific antigen, the section is treated with primary antiserum, washed, and then treated with secondary antiserum; the subsequent addition of ABC localizes peroxidase at the site of specific antigen (since the

(1) Adenine (or the corresponding nucleoside or nucleotide) in a nucleic acid. (2) Alanine (see AMINO ACIDS). ˚ ˚ (Angstr¨ A om unit) 10−10 m (= 10−1 nm). 2–5A See INTERFERONS. A-DNA See DNA. a-factor See MATING TYPE. A layer An S LAYER associated with virulence in strains of Aeromonas salmonicida. A-protein In TOBACCO MOSAIC VIRUS: a mixture of small oligomers and monomers of coat protein subunits which occur in equilibrium with the larger ‘disc’ aggregates under conditions of physiological pH and ionic strength; coat protein occurs mainly as A-protein under conditions of high pH and low ionic strength. (cf. PROTEIN A.) A site (of a ribosome) See PROTEIN SYNTHESIS. A-tubule (A-subfibre) See FLAGELLUM (b). A-type inclusion body See POXVIRIDAE. A-type particles Intracellular, non-infectious, retrovirus-like particles. Many embryonic and transformed mouse cells contain retrovirus-like ‘intracisternal A-type particles’ (IAPs) which form by budding at the endoplasmic reticulum; these particles have reverse transcriptase activity and an RNA genome coding for the structural protein of the particles. The mouse genome contains ca. 1000 copies (per haploid genome) of DNA sequences homologous to IAP-associated RNA; these sequences appear to be capable of transposition within the mouse genome – probably via an RNA intermediate [Book ref. 113, pp. 273–279], i.e., they may be RETROTRANSPOSONS. Some A-type particles are non-enveloped precursors of B-type particles (see TYPE B ONCOVIRUS GROUP). A23187 An IONOPHORE which transports divalent cations, particularly Ca2+ ; it can effect the transmembrane exchange of 1Ca2+ (or 1Mg2+ ) for 2H+ without causing perturbation in the gradients of other monovalent cations. AAA ATPases ‘ATPases associated with diverse cellular activities’. AAA ATPases occur e.g. in PEROXISOMES and as components of eukaryotic PROTEASOMES. AAA pathway AMINOADIPIC ACID PATHWAY. AAC Aminoglycoside acetyltransferase (see AMINOGLYCOSIDE ANTIBIOTICS). AAD Aminoglycoside adenylyltransferase (see AMINOGLYCOSIDE ANTIBIOTICS). AAS Aminoalkylsilane (3-aminopropyltriethoxy-silane, APES; 3(triethoxysilyl)-propylamine, TESPA): a reagent used for binding a tissue section to the surface of a glass slide (e.g. for in situ hybridization); it reacts with silica glass and provides aminoalkyl groups which bind to aldehyde or ketone groups in the tissue section. aat gene In Escherichia coli: a gene whose product promotes the early degradation of those proteins whose N-terminal amino acid is either arginine or lysine. aat encodes an ‘amino acid transferase’ which catalyses the addition of a leucine or phenylalanine residue to the N-terminus of the protein; this destabilizes the protein, facilitating its degradation. (See also N-END RULE.) AatII See RESTRICTION ENDONUCLEASE (table). Aaterra See ETRIDIAZOLE. AAUAAA locus See MRNA (b). AAV Adeno-associated virus: see DEPENDOVIRUS. ab (immunol.) ANTIBODY. 1

ABC protein ABC adheres non-specifically to biotin). Peroxidase (and hence antigen) is detected by incubating the section with e.g. H2 O2 and diaminobenzidine (which results in the antigenic site being stained brown) or H2 O2 and 4-chloro-1-naphthol (resulting in a blue stain). The ABC method can be used for paraffin-embedded sections, frozen sections, and smears. Endogenous (tissue or cell) peroxidase may be quenched e.g. with H2 O2 in methanol. ABC protein See ABC TRANSPORTER. ABC transporter (traffic ATPase) A type of TRANSPORT SYSTEM which, in bacteria, consists typically of a multiprotein complex in the cell envelope, two of the proteins having a specific ATPbinding site (termed the ATP-binding cassette; ABC) on their cytoplasmic surface; a (bacterial) protein with an ABC site has been called an ‘ABC protein’ or an ‘ABC subunit’. In eukaryotes, an ABC transporter generally consists of a single polypeptide chain – which also has two ATP-binding sites. Transport mediated by an ABC transporter is energized by ATP hydrolysis at the ABC sites. [ATP-hydrolysing regions of ABC transporters: FEMS Reviews (1998) 22 1–20.] (See also PROTEIN SECRETION.) A given type of ABC transporter imports or exports/secretes certain type(s) of ion or molecule. Collectively, these transporters import or secrete a wide range of substances, including ions, sugars and proteins; for example, some import nutrients, or ions for OSMOREGULATION, while others secrete antibiotics or protein toxins. The LmrA transporter in Lactococcus lactis mediates an efflux system that extrudes amphiphilic compounds and appears to be functionally identical to the mammalian Pglycoprotein that mediates multidrug-resistance [Nature (1998) 391 291–295]. The AtrB transporter of Aspergillus nidulans mediates energy-dependent efflux of a range of fungicides [Microbiology (2000) 146 1987–1997]. ABC transporters occur e.g. in Gram-positive and Gramnegative bacteria, members of the Archaea, and in higher animals, including man. In man, certain inheritable diseases (e.g. CYSTIC FIBROSIS and adrenoleukodystrophy) result from defective ABC transporters. The bacterial ABC importer is commonly called a BINDING PROTEIN-DEPENDENT TRANSPORT SYSTEM (q.v.). (See also ABC EXPORTER.) ABE process An industrial process in which acetone, butanol and ethanol are produced by the fermentation of e.g. molasses by Clostridium acetobutylicum. (See also ACETONE–BUTANOL FERMENTATION.) Abelson murine leukaemia virus (Ab-MuLV) A replicationdefective, v-onc+ MURINE LEUKAEMIA VIRUS isolated from a prednisolone-treated BALB/c mouse inoculated with Moloney murine leukaemia virus (Mo-MuLV). Ab-MuLV apparently arose by recombination between Mo-MuLV and mouse c-abl sequences; the v-abl product has tyrosine kinase activity. (See also ABL.) Ab-MuLV induces B-cell lymphoid leukaemia with a short latent period (3–4 weeks). [Abelson virus–cell interactions: Adv. Imm. (1985) 37 73–98.] abequose (3,6-dideoxy-D-galactose) A sugar, first isolated from Salmonella abortusequi, which occurs in the O-specific chains of the LIPOPOLYSACCHARIDE in certain Salmonella serotypes and which contributes to the specificity of O antigen 4 in group B salmonellae (see KAUFFMANN–WHITE CLASSIFICATION). aberration (chromosomal) See CHROMOSOME ABERRATION. abhymenial Of or pertaining to a region opposite or away from the HYMENIUM. abiogenesis (spontaneous generation) The spontaneous formation of living organisms from non-living material; apart from

its application to the evolutionary origin of life, this doctrine has long been abandoned. abiotic Non-living; of non-biological origin. abl An ONCOGENE originally identified as the transforming determinant of ABELSON MURINE LEUKAEMIA VIRUS (Ab-MuLV). The v-abl product has tyrosine kinase activity. In humans, c-abl normally occurs on chromosome 9, but is translocated to chromosome 22q- (the Philadelphia chromosome) in cells from patients with chronic myelogenous leukaemia (CML); in chromosome 22 it forms a chimeric fusion gene, bcr-abl, encoding a tumour-specific tyrosine kinase designated P210. ablastin Antibody which specifically inhibits reproduction of epimastigote forms of Trypanosoma lewisi in the vertebrate host. abomasitis Inflammation of the abomasum. (See also BRAXY; cf. RUMENITIS.) abomasum See RUMEN. aboral Away from, or opposite to, the mouth. abortifacient Able to cause abortion. abortive infection (virol.) A viral infection of (non-permissive) cells which does not result in the formation of infectious progeny virions, even though some viral genes (e.g. early genes) may be expressed. (cf. PERMISSIVE CELL.) abortive transduction See TRANSDUCTION. abortus Bang reaction (abortus Bang ring-probe) Syn. MILK RING TEST. ABR See MILK RING TEST. abrB gene See ENDOSPORE (figure (a) legend). abscess A localized collection of PUS surrounded by inflamed and necrotic tissue; it may subside spontaneously or may rupture and drain before healing. Abscesses may occur in any tissue and may be caused by any of a variety of organisms. Abscesses in internal organs (e.g. liver, kidney, brain) may follow bacteraemia or septicaemia and may be due to staphylococci, streptococci, coliforms, etc. A cold (or chronic) abscess is one with little inflammation, often due to tubercle bacilli. (See also DYSENTERY (b) and QUINSY.) abscisic acid (ABA) A terpenoid PHYTOHORMONE which acts e.g. as a growth inhibitor, as an inhibitor of germination, and as an accelerator of e.g. leaf abscission. ABA is also formed (as a secondary metabolite) e.g. by the fungus Cercospora rosicola. Absidia See MUCORALES. absorption (serol.) The removal or effective removal of particular antibodies, antigens, or other agents from a given sample (e.g. serum) by the addition of particular antigens, antibodies, or agents to that sample; the resulting antigen–antibody (or other) complexes may or may not be physically removed from the sample. Absorption is used e.g. to remove HETEROPHIL ANTIBODIES. absorptive pinocytosis See PINOCYTOSIS. 7-ACA 7-Aminocephalosporanic acid (see CEPHALOSPORINS). Acanthamoeba A genus of amoebae (order AMOEBIDA) in which the pseudopodia each have a broad hyaline zone (see PSEUDOPODIUM) from which arise several to many slender, tapering, flexible, and sometimes forked projections (acanthopodia). Polyhedral or roughly circular cysts with cellulose-containing walls are formed. Species are widespread and common in soil and fresh water, where they prey on e.g. bacteria, yeasts etc. [Adhesion of Acanthamoeba castellanii to bacterial flagella: JGM (1984) 130 1449–1458; bacterial endosymbionts of Acanthamoeba: J. Parasitol. (1985) 71 89–95.] Some strains can cause e.g. eye infections, MENINGOENCEPHALITIS [pathogenicity: RMM (1994) 5 12–20]. (cf. HARTMANNELLA.) 2

Acetobacter Acantharea A class of marine, mostly planktonic protozoa (superclass ACTINOPODA) which have elaborate ‘skeletons’ composed of strontium sulphate; typically, the skeleton consists of 10 spines arranged diametrically in the (more or less spherical) cell, or 20 spines which radiate from the cell centre (where they may or may not be joined at their bases, according to species). In many species the cell contains a central capsule (cf. RADIOLARIA); many species contain zooxanthellae. Five orders are recognized; genera include e.g. Acanthochiasma, Acanthometra, Astrolophus, Gigartacon. Acanthochiasma See ACANTHAREA. Acanthocystis See CENTROHELIDA. Acanthoeca See CHOANOFLAGELLIDA. Acanthometra See ACANTHAREA. acanthopodia See ACANTHAMOEBA. acaricide Any chemical which kills mites and ticks (order Acarina). Acarospora A genus of LICHENS (order LECANORALES). Thallus: crustose, areolate, with prominent areolae. Apothecia are embedded in the areolae; ascospores: very small, many per ascus. All species are saxicolous, some are ENDOLITHIC; A. smaragdula occurs on rocks and slag rich in heavy metals. Acarpomyxea A class of protozoa (superclass RHIZOPODA) with characteristics intermediate between those of the naked amoebae and the plasmodial slime moulds: they form small plasmodia (or large uninucleate plasmodium-like forms) which are usually branched and which sometimes anastomose to form a coarse reticulum. Spores, fruiting bodies and tests are absent; cysts are produced by some species. Orders: Leptomyxida (soil and freshwater organisms, e.g. Leptomyxa [Book ref. 133, pp. 143–144], Rhizamoeba) and Stereomyxida (marine organisms, e.g., Corallomyxa, Stereomyxa). Acaryophrya See GYMNOSTOMATIA. Acaulopage See e.g. NEMATOPHAGOUS FUNGI. Acaulospora See ENDOGONALES. acceptor site (of a ribosome) See PROTEIN SYNTHESIS. acceptor splice site See SPLIT GENE (a). accessory cells (immunol.) Those cells which, together with B LYMPHOCYTES and/or T LYMPHOCYTES, are involved in the expression of humoral and/or cell-mediated immune responses; they include e.g. MACROPHAGES, DENDRITIC CELLS, and LANGERHANS’ CELLS. accessory pigments In PHOTOSYNTHESIS: those pigments contained in LIGHT-HARVESTING COMPLEXES. AcCoA Acetyl-COENZYME A. Ace toxin (Vibrio cholerae) See BACTERIOPHAGE CTX8. acellular (non-cellular) (1) Refers to an organism, usually a protozoon, which consists essentially of a single cell but in which occur functionally specialized regions sometimes regarded as analogous to the organs and tissues of a differentiated multicellular organism. (2) Refers to an organism (e.g. a VIRUS) or structure (e.g. the stalk of ACYTOSTELIUM) which is not CELLULAR in any sense. (3) Not divided into cells (as e.g. in a PLASMODIUM). acellular slime moulds See MYXOMYCETES. acentric (of a chromosome) Having no CENTROMERE. acephaline gregarines See GREGARINASINA. acer tar spot See RHYTISMA. acervulus A flat or saucer-shaped fungal STROMA supporting a mass of typically short and densely-packed conidiophores; acervuli commonly develop subcuticularly or subepidermally in a plant host, becoming erumpent at maturity, i.e., rupturing the overlying plant tissue to allow dispersal of the conidia. Some acervuli bear setae (see SETA).

Acetabularia A genus of DASYCLADALEAN ALGAE. The vegetative thallus consists of a single cell in which the CELL WALL contains MANNAN as a major component and is generally more or less heavily calcified; the cell is differentiated into an erect stalk or axis (up to several centimetres tall) anchored to the substratum by a branching rhizoid. The single nucleus is located in one branch of the rhizoid. As the stalk grows, whorls of sterile ‘hairs’ develop around the tip; these hairs are eventually shed, leaving rings of scars around the stalk. When the thallus is mature, gametangia develop as an apical whorl of elongated sac-like structures which, depending on species, may or may not be joined to form a characteristic cap (giving rise to the popular name ‘mermaid’s wine-glass’). Once the gametangial sacs have developed, the primary nucleus in the rhizoid grows to ca. 20 times its original size; it then undergoes meiosis, and numerous small secondary nuclei are formed. These migrate from the rhizoid to the gametangia by cytoplasmic streaming. Within a gametangial sac, each nucleus becomes surrounded by a resistant wall, resulting in the formation of many resistant cysts; the cyst walls contain cellulose rather than mannan, and are often heavily calcified. The cysts are liberated into the sea and then undergo a period of dormancy before liberating numerous biflagellate isogametes; pairs of gametes fuse to form zygotes which then develop into new vegetative thalli. acetate formation See e.g. ACETIFICATION and ACETOGENESIS. acetate thiokinase See METHANOGENESIS. acetate utilization See e.g. METHANOGENESIS and TCA CYCLE. Acetator See VINEGAR. acetic acid bacteria (1) Acetobacter spp. (2) Any bacteria capable of ACETIFICATION, including Acetobacter spp and Gluconobacter sp. aceticlastic Able to catabolize acetate. acetification The aerobic conversion of ethanol to acetic acid by bacteria (usually Acetobacter spp). Ethanol is converted to hydrated acetaldehyde (CH3 CH(OH)2 ) which is then dehydrogenated to give acetic acid. Acetification is an exothermic process. (See also e.g. VINEGAR, BEER SPOILAGE, WINE SPOILAGE.) Acetivibrio A genus of bacteria (family BACTEROIDACEAE) whose natural habitat is unknown. Cells: straight to slightly curved rods, 0.5–0.9 × 1.5–10.0 µm; in motile species the concave side of the cell has either a single flagellum or a number of flagella which arise in a line along the longitudinal axis of the cell. The cells stain Gram-negatively but the cell wall of the type species resembles those of Gram-positive bacteria. The major products of carbohydrate fermentation typically include acetic acid, ethanol, CO2 and H2 ; butyric, lactic, propionic and succinic acids are not formed. GC%: ca. 37–40. Type species: A. cellulolyticus. A. cellulolyticus. Monotrichous. Substrates include cellobiose, cellulose and salicin; aesculin is not hydrolysed. The type strain was isolated from a methanogenic enrichment culture. A. cellulosolvens. A non-motile species (isolated from sewage sludge) which can hydrolyse cellulose, cellobiose, aesculin and salicin; the cells apparently have an outer membrane. [IJSB (1984) 34 419–422.] A. ethanolgignens. Multitrichous. Substrates include fructose, galactose, lactose, maltose, mannitol and mannose – but not cellobiose, cellulose or aesculin. A. ethanolgignens is consistently present in the colons of pigs suffering from SWINE DYSENTERY. Acetobacter A genus of Gram type-negative bacteria of the family ACETOBACTERACEAE; the organisms occur e.g. on certain fruits and flowers, are responsible for some types of BEER SPOILAGE and WINE SPOILAGE, and are used e.g. in the manufacture of VINEGAR. 3

Acetobacteraceae Cells: typically ovoid or rod-shaped, 0.6–0.8 × 1.0–4.0 µm, non-motile or with peritrichous or lateral flagella. Most strains are catalase-positive. Typically, ethanol is oxidized to acetic acid, and acetic acid is oxidized (‘overoxidation’) to CO2 (cf. GLUCONOBACTER). Principal substrates include e.g. ethanol, glycerol and lactate; most strains grow well on glucose–yeast extract–CaCO3 agar (GYC agar), forming round pale colonies. (See also CARR MEDIUM.) Some strains form CELLULOSE (see PELLICLE (1)). Sugars appear to be metabolized primarily via the HEXOSE MONOPHOSPHATE PATHWAY and the TCA CYCLE; phosphofructokinase seems to be absent (cf. Appendix I(a)). The ENTNER–DOUDOROFF PATHWAY appears to occur only in cellulosesynthesizing strains. Growth on HOYER’S MEDIUM appears to involve enzymes of the glyoxylate shunt. Optimum growth temperature: 25–30° C. GC%: ca. 51–65. Type species: A. aceti. A. aceti. Ketogenic with glycerol or sorbitol substrates; 5-ketogluconic acid (but not 2,5-diketogluconic acid) formed from D-glucose. No diffusible brown pigments are formed on GYC agar. Grows on sodium acetate. A. hansenii. Ketogenic with glycerol or sorbitol substrates; 5ketogluconic acid (but not 2,5-diketogluconic acid) is formed by some strains from D-glucose. No growth on sodium acetate. No diffusible brown pigments are formed on GYC agar. (cf. A. xylinum.) A. liquefaciens. Brown diffusible pigments are formed on GYC agar. 2,5-Diketogluconic acid is formed from D-glucose. Ketogenic with glycerol as substrate. A. pasteurianus. Ketogluconic acids are not formed from Dglucose. No brown diffusible pigments are formed on GYC agar. Some strains (formerly called A. peroxydans) are catalasenegative. (cf. A. xylinum.) A. peroxydans. See A. pasteurianus. A. suboxydans. See GLUCONOBACTER. A. xylinum. Cellulose-producing strains formerly classified as a subspecies of A. aceti, then distributed between the two species A. hansenii and A. pasteurianus; A. xylinum has now been accepted as a revived name for cellulose-forming and celluloseless, acetate-oxidizing strains [IJSB (1984) 34 270–271]. [Book ref. 22, pp. 268–274.] Acetobacteraceae A family of aerobic, oxidase-negative, chemoorganotrophic, Gram type-negative bacteria which typically oxidize ethanol to acetic acid. Metabolism: strictly respiratory (oxidative), with O2 as terminal electron acceptor. Growth occurs optimally at ca. pH 5–6. The organisms occur e.g. in acidic, ethanol-containing habitats. GC%: ca. 51–65. Two genera: ACETOBACTER (type genus), GLUCONOBACTER [Book ref. 22, pp. 267–278]. Acetobacterium A genus of Gram-negative, obligately anaerobic bacteria which occur in marine and freshwater sediments [IJSB (1977) 27 355–361]. Cells: polarly flagellated ovoid rods, ca. 1.0 × 2.0 µm, often in pairs. The type species, A. woodii, can carry out a homoacetate fermentation of e.g. fructose, glucose or lactate, or can grow chemolithoautotrophically (see ACETOGENESIS); it contains group B PEPTIDOGLYCAN. Optimum growth temperature: 30° C. GC%: ca. 39. (See also ANAEROBIC DIGESTION.) acetogen (1) Any bacterium (e.g. Acetobacterium woodii, Clostridium aceticum, C. thermoaceticum) which produces acetate – as the main product – from certain sugars (via homoacetate fermentation and reduction of carbon dioxide) and (in some strains) from carbon dioxide and hydrogen (see ACETOGENESIS). (2) (hydrogenogen; proton-reducing acetogen) Any bacterium which can use protons as electron acceptors for the

oxidation of certain substrates (e.g. ethanol, lactate, fatty acids) to acetate with concomitant formation of hydrogen. Obligate hydrogenogens include e.g. SYNTROPHOMONAS (see also ANAEROBIC DIGESTION). Some SULPHATE-REDUCING BACTERIA appear to be facultative hydrogenogens. The synthesis of acetate by hydrogenogens is thermodynamically favourable only when the partial pressure of hydrogen is very low – e.g. in the presence of a hydrogen-utilizing methanogen. acetogenesis Acetate formation. A variety of microorganisms can form acetate, as a major or minor product, e.g. via the MIXED ACID FERMENTATION or PROPIONIC ACID FERMENTATION. (cf. ACETIFICATION.) The term is also used more specifically to refer to the particular pathways used by the ACETOGENS (sense 1). These organisms form acetate, as the main product, from e.g. certain hexoses in a process (homoacetate fermentation) in which the hexose is metabolized to pyruvate (via the EMBDEN–MEYERHOF–PARNAS PATHWAY) and thence to acetate and carbon dioxide. Additional acetate is formed as follows. Some of the carbon dioxide is reduced to formate; this formate is bound to tetrahydrofolate (THF) and is further reduced (in an ATP-dependent reaction) to yield 5-methyl-THF. The methyl group is then transferred to coenzyme B12 . The remainder of the carbon dioxide is reduced to carbon monoxide (by CO dehydrogenase). Carbon monoxide reacts with methyl-coenzyme B12 in the presence of coenzyme A and CO dehydrogenase disulphide reductase to yield acetyl-CoA. Acetyl-CoA is converted to acetate and CoASH with concomitant substrate-level phosphorylation to yield ATP. Some acetogens (e.g. A. woodii, C. aceticum, some strains of C. thermoaceticum) can form acetate from carbon dioxide and hydrogen [autotrophic pathways in acetogens: JBC (1986) 261 1609–1615]. This process resembles the latter part of the pathway above: CO is derived from carbon dioxide, 2H+ and 2e− , and 5-methyl-THF from THF, carbon dioxide and hydrogen. acetoin (CH3 .CHOH.CO.CH3 ; acetylmethylcarbinol) See e.g. Appendix III(c); BUTANEDIOL FERMENTATION; VOGES–PROSKAUER TEST. Acetomonas Former name of GLUCONOBACTER. acetone–butanol fermentation (solvent fermentation) A FERMENTATION (sense 1), carried out by certain saccharolytic species of Clostridium (e.g. C. acetobutylicum), in which the products include acetone (or isopropanol) and n-butanol (collectively referred to as ‘solvent’). Glucose is initially metabolized via the BUTYRIC ACID FERMENTATION, but subsequently the pH drops to ca. 4.5–5.0 and acetone and n-butanol are formed as major end products [Appendix III (g)]. This fermentation is carried out on an industrial scale to a limited extent. [Review: AAM (1986) 31 24–33, 61–92.] acetosyringone See CROWN GALL. 3-acetoxyindole See INDOXYL ACETATE. acetylcholine (neurotransmitter) See BOTULINUM TOXIN. acetyl-CoA synthetase See TCA CYCLE. N-acetyl-L-cysteine See MUCOLYTIC AGENT. N-acetyl-D-glucosamine (GlcNAc) N-Acetyl-(2-amino-2-deoxyD-glucose): an amino sugar present in various polysaccharides – see e.g. CHITIN, HYALURONIC ACID, LIPOPOLYSACCHARIDE, PEPTIDOGLYCAN (q.v. for formula), TEICHOIC ACIDS. acetylmethylcarbinol Syn. ACETOIN. N-acetylmuramic acid See PEPTIDOGLYCAN. N-acetylmuramidase Syn. LYSOZYME. N-acetylneuraminic acid See NEURAMINIC ACID. 4

Acinetobacter A-CGT See IMMUNOSORBENT ELECTRON MICROSCOPY. achlorophyllous Syn. ACHLOROTIC. achlorotic (achlorophyllous) Lacking chlorophyll. (cf. APOCHLOROTIC.) Achlya A genus of aquatic fungi (order SAPROLEGNIALES) in which the thallus is characteristically a branched, coenocytic mycelium; the width of the hyphae varies with species. Although Achlya species are typically saprotrophic some have been reported to parasitize rice plants. (See also DIPLANETISM, HETEROTHALLISM and PHEROMONE.) Achnanthes See DIATOMS. Acholeplasma A genus of facultatively anaerobic, ureasenegative bacteria (family ACHOLEPLASMATACEAE) which are associated with various vertebrates (and possibly with invertebrates and plants), and which also occur e.g. in soil and sewage and as contaminants in TISSUE CULTURES. Cells: non-motile cocci (minimum diam. ca. 300 nm) or filaments (typically ca. 2–5 µm in length); carotenoid pigments occur in some species. The organisms resemble Mycoplasma spp in their general properties, but differ e.g. in that their growth is sterol-independent, and in that NADH oxidase occurs in the cytoplasmic membrane rather than in the cytoplasm. Acholeplasma spp are susceptible to various ACHOLEPLASMAVIRUSES. GC%: ca. 26–36. Type species: A. laidlawii; other species: A. axanthum, A. equifetale, A. granularum, A. hippikon, A. modicum, A. morum, A. oculi. [Book ref. 22, pp. 775–781.] Acholeplasmataceae A family of bacteria of the order MYCOPLASMATALES; species of the sole genus, ACHOLEPLASMA, differ from the other members of the order e.g. in that their growth is not sterol-dependent. [Proposal for re-classifying Acholeplasmataceae as the order Acholeplasmatales: IJSB (1984) 34 346–349.] acholeplasmaviruses BACTERIOPHAGES which infect Acholeplasma species: see PLECTROVIRUS, PLASMAVIRIDAE, MV-L3 PHAGE GROUP. achromat (achromatic objective) An objective lens (see MICROSCOPY) in which chromatic aberration has been corrected for two colours (usually red and blue), and spherical aberration has been corrected for one colour (usually yellow–green). (cf. APOCHROMAT.) A FLAT-FIELD OBJECTIVE LENS of this type is called a planachromat. Achromobacter An obsolete bacterial genus. achromogenic Refers to an organism (or e.g. reagent) which does not produce pigment (or colour); used e.g. of non-pigmented strains of normally CHROMOGENIC organisms. achromycin See TETRACYCLINES. aciclovir A spelling used by some authors for the drug ACYCLOVIR. acicular Needle-shaped. Aciculoconidium A genus of fungi (class HYPHOMYCETES) which form budding ovoid or ellipsoidal cells (occurring singly or in short chains or clusters) as well as branched septate hyphae. Conidia are formed terminally and are acicular, rounded at one end and pointed at the other. NO3 − is not assimilated. One species: A. aculeatum (formerly Trichosporon aculeatum), isolated from Drosophila spp. [Book ref. 100, pp. 558–561.] acid dye See DYE. acid-fast organisms Organisms (e.g. Mycobacterium spp) which, once stained with an ACID-FAST STAIN, cannot be decolorized by mineral acids or by mixtures of acid and ethanol. acid-fast stain Any stain used to detect or demonstrate ACID-FAST ORGANISMS – e.g. ZIEHL–NEELSEN’S STAIN, AURAMINE–RHODAMINE STAIN.

acid fuchsin See FUCHSIN. acid phosphatase See PHOSPHATASE. Acidaminococcus A genus of Gram-negative bacteria (family VEILLONELLACEAE) which occur e.g. in the intestine in humans and pigs. Cells: typically kidney-shaped cocci, 0.6–1.0 µm diam, occurring in pairs. Amino acids are the main sources of carbon and energy; all strains need e.g. arginine, glutamate, tryptophan and valine, and most need e.g. cysteine and histidine. In general, the organisms metabolize carbohydrates weakly or not at all. Optimum growth temperature: 30–37° C. Optimum pH: 7.0. GC%: ca. 57. Type species: A. fermentans. acidophile An organism which grows optimally under acidic conditions, having an optimum growth pH below 6 (and sometimes as low as 1, or below), and which typically grows poorly, or not at all, at or above pH 7: see e.g. SULFOLOBUS, THERMOPLASMA, THIOBACILLUS. (cf. ALKALOPHILE and NEUTROPHILE; see also LEACHING.) acidophilus milk A sour, medicinal beverage made by fermenting heat-treated, partially skimmed milk with Lactobacillus acidophilus. (Viable L. acidophilus appears to have a therapeutic effect on some intestinal disorders.) The main fermentation product is lactic acid which reaches a level of ca. 1.0%. A more palatable preparation, ‘sweet acidophilus milk’, is made by adding L. acidophilus to milk at ca. 5° C; under these conditions the cells remain viable but lactic acid is not produced. (See also DAIRY PRODUCTS.) acidosis (1) (lactic acidosis) (vet.) A (sometimes fatal) condition which may occur in ruminants fed excessive amounts of readily fermentable carbohydrates (e.g. starch, sugars – found e.g. in grain and beet, respectively) or when the transfer from a roughage to a ‘concentrate’ diet is made too quickly. Under these conditions the rate of acid production in the RUMEN is very high; the resulting fall in pH in the rumen (due mainly to the accumulation of lactic acid) inhibits cellulolytic bacteria and protozoa, and favours the growth of certain LACTIC ACID BACTERIA – so that the pH falls still further. (See also RUMENITIS.) A gradual transition from roughage to concentrate may permit the somewhat more acid-tolerant bacterium Megasphaera elsdenii to metabolize the lactic acid and maintain a normal pH in the rumen. (See also THIOPEPTIN.) (2) (med., vet.) A pathological condition characterized by an abnormally low pH in the blood and tissues. Acidothermus A proposed genus of aerobic, thermophilic (growing at 37–70° C), acidophilic (growing at pH 3.5–7.0), cellulolytic, non-motile, rod-shaped to filamentous bacteria isolated from acidic hot springs; GC%: ca. 60.7. [IJSB (1986) 36 435–443.] aciduric Tolerant of acidic conditions. (cf. ACIDOPHILE.) Acineria See GYMNOSTOMATIA. Acineta See SUCTORIA. Acinetobacter A genus of strictly aerobic, oxidase −ve, catalase +ve Gram-type-negative bacteria of the family MORAXELLACEAE (within the gamma subdivision of PROTEOBACTERIA); the organisms occur e.g. in soil and water and may act as opportunist pathogens in man. (See also MEAT SPOILAGE and SEWAGE TREATMENT.) Cells: short rods, 0.9–1.6 × 1.5–2.5 µm, or coccobacilli (coccoid in stationary-phase cultures); cells often in pairs. Nonmotile, but may exhibit TWITCHING MOTILITY. Non-pigmented. Metabolism is respiratory (oxidative), with oxygen as terminal electron acceptor; no growth occurs anaerobically, with or without nitrate. 5

AcLVs Most strains can grow on a mineral salts medium containing an organic carbon source such as acetate, ethanol or lactate as the sole source of carbon and energy; some can use amino acids (e.g. L-leucine, ornithine) and/or pentoses (e.g. Larabinose, D-xylose), and some are able to degrade e.g. benzoate, n-hexadecane and alicyclic compounds (see HYDROCARBONS). Acinetobacters appear to contain all the enzymes of the TCA CYCLE and the glyoxylate cycle. Many carbohydrates can be used. Most strains in the A. calcoaceticus–A. baumannii complex (and in certain other groups) can form acid from glucose (oxidatively), but many (e.g. most strains designated A. lwoffii ) cannot. The optimal growth temperature is typically 33–35° C. GC%: ∼38–47. Type species: A. calcoaceticus. The taxonomy of Acinetobacter is confused and unsatisfactory. Emended descriptions of the two species A. calcoaceticus and A. lwoffii, and proposals for four new species (A. baumannii, A. haemolyticus, A. johnsonii and A. junii ), were published in 1986 [IJSB (1986) 36 228–240]. Since then, a number of adjustments have been made to the taxonomic structure of the genus. [Taxonomy, and epidemiology of Acinetobacter infections: RMM (1995) 6 186–195.] Acinetobacters have been isolated in a number of hospitalassociated (and other) outbreaks of disease, often as part of a mixed infection; in most cases such infections involve glucolytic strains of the A. calcoaceticus–A. baumannii complex – particularly A. baumannii (also called group 2, or genospecies 2). The most common manifestations of disease include septicaemia and infections of the urinary tract, lower respiratory tract and central nervous system. Transmission may occur by direct contact or may involve the airborne route. Acinetobacters have been reported to survive on dry surfaces for at least as long as e.g. Staphylococcus aureus. One problem associated with the pathogenic role of Acinetobacter is that these organisms appear easily to acquire resistance to antibiotics – so that they have the potential to develop as multiresistant pathogens; currently, for example, acinetobacters are reported to be resistant to most b-lactam antibiotics, particularly penicillins and cephalosporins, and to chloramphenicol and trimethoprim–sulphamethoxazole. [Mechanisms of antimicrobial resistance in A. baumannii: RMM (1998) 9 87–97.] AcLVs AVIAN ACUTE LEUKAEMIA VIRUSES. acne A chronic skin disorder characterized by increased sebum production and the formation of comedones (‘blackheads’ and ‘whiteheads’) which plug the hair follicles. Propionibacterium acnes, present in the pilosebaceous canal (see SKIN MICROFLORA), may play a causal role; it produces a lipase that hydrolyses sebum triglycerides to free fatty acids, and these can cause inflammation and comedones [JPed (1983) 103 849–854]. Treatment: e.g. topical SALICYLIC ACID or benzoyl peroxide; the latter has keratinolytic activity and exerts bactericidal action on P. acnes by releasing free-radical oxygen. Aconchulinida See FILOSEA. aconitase See Appendix II(a) and NITRIC OXIDE. Aconta Algae of the RHODOPHYTA. (cf. CONTOPHORA.) acquired immune deficiency syndrome See AIDS. acquired immunity (1) SPECIFIC IMMUNITY acquired through exposure to a given antigen. (2) PASSIVE IMMUNITY. (3) NONSPECIFIC IMMUNITY acquired through exposure to certain viruses (see e.g. INTERFERONS) or by immunization with BCG. Acrasea See ACRASIOMYCETES. acrasids See ACRASIOMYCETES. acrasin In cellular slime moulds: a generic term for a chemotactic substance which is produced by cells and which serves

as a chemoattractant for cell aggregation. Acrasins are a diverse group of substances; they include cAMP in Dictyostelium discoideum (q.v.), a pterin in Dictyostelium lacteum [PNAS (1982) 79 6270–6274], and a dipeptide, ‘glorin’, in Polysphondylium violaceum (q.v.). Acrasiomycetes (acrasid cellular slime moulds; acrasids) A class of cellular SLIME MOULDS (division MYXOMYCOTA) in which the vegetative phase consists of amoeboid cells that form lobose pseudopodia; the amoebae aggregate (without streaming) to form a pseudoplasmodium which is not slug-like and does not migrate (cf. DICTYOSTELIOMYCETES). The pseudoplasmodium gives rise to multispored fruiting bodies which may have long or short stalks (but no cellulosic stalk tube) bearing e.g. simple globular sori or branched or unbranched chains of spores. Flagellated cells have been observed in only one species (Pocheina rosea). Sexual processes are unknown. Acrasids occur in various habitats: e.g. dung, tree-bark, dead plant materials, etc. Genera include Acrasis, Copromyxa, Copromyxella, Fonticula, Guttulinopsis, Pocheina (formerly Guttulina). (Zoological taxonomic equivalents of the Acrasiomycetes include the class Acrasea of the MYCETOZOA, and the class Acrasea of the RHIZOPODA.) Acrasis See ACRASIOMYCETES. Acremonium A genus of fungi of the class HYPHOMYCETES; teleomorphs occur in e.g. Emericellopsis and Nectria. The genus includes organisms formerly classified as species of Cephalosporium [for references see MS (1986) 3 169–170]. Acremonium spp form septate mycelium; conidia, often in gelatinous masses, are produced from phialides which develop from simple, single branches of the vegetative hyphae. A. kiliense (= Cephalosporium acremonium) produces cephalosporin C (see CEPHALOSPORINS). (See also MADUROMYCOSIS.) acridine orange (basic orange, or euchrysine; 3,6-bis(dimethylamino)-acridinium chloride) A basic dye and FLUOROCHROME used e.g. in fluorescence MICROSCOPY to distinguish between dsDNA (which fluoresces green) and ss nucleic acids (which fluoresce orange-red). Sublethal concentrations of the dye are used for CURING plasmids. (See also ACRIDINES.) acridines Heterocyclic compounds which include acridine and its derivatives. At low concentrations, aminoacridines (e.g. proflavine (3,6-diaminoacridine), QUINACRINE) appear to bind to dsDNA (or to double-stranded regions of ssDNA) primarily as INTERCALATING AGENTS. At higher concentrations there is also a weaker, secondary type of binding in which the acridine binds to the outside of dsDNA or to ssDNA or ssRNA; the two types of binding may account for the differential staining of DNA and RNA by ACRIDINE ORANGE. [Book ref. 14, pp. 274–306.] Acridines inhibit DNA and RNA synthesis and cause e.g. FRAMESHIFT MUTATIONS. They are used e.g. as antimicrobial agents (see e.g. ACRIFLAVINE), as mutagens, and as fluorescent stains for nucleic acids; they also have potential antitumour activity. (See also CURING (2).) As antimicrobial agents, acridines are active against a wide range of bacteria, but they are not sporicidal; some are active against certain parasitic protozoa (see e.g. QUINACRINE and KINETOPLAST) and inhibit the replication of certain viruses. Activity is not significantly affected by proteinaceous matter. [Acridines as antibacterials (review): JAC (2001) 47 1–13.] As mutagens, acridines may be effective in replicating bacteriophages but are generally not effective in bacteria. However, compounds in which an acridine nucleus is linked to an alkylating side-chain – ICR compounds (ICR = Institute for Cancer Research) – can induce frameshift and other mutations in bacteria. 6

actinoidin (6)

(5)

(4)

8

9

1

(7) 7

(8) 6 5

(9)

N

10

(10)

2

(3)

3

(2)

The formation and fate of microfilaments are regulated in vivo e.g. by various proteins. Profilin binds to G-actin, inhibiting polymerization. Gelsolin (in e.g. macrophages), severin (in Dictyostelium), fragmin (in Physarum), and villin (in microvilli) can each cleave F-actin into fragments in a Ca2+ -dependent reaction, thereby e.g. effecting a gel-to-sol transition. Filamin and a-actinin can cross-link microfilaments, promoting gel formation. b-Actinin can act as a CAPPING (sense 2) protein. Vinculin may help to anchor microfilaments to other cell components. [Binding of microfilaments to the cytoplasmic membrane in Dictyostelium discoideum: JCB (1986) 102 2067–2075.] Fimbrin binds together longitudinally adjacent microfilaments to form bundles. Actin polymerization/depolymerization is affected e.g. by agents such as CYTOCHALASINS and by phalloidin (see PHALLOTOXINS). (2) See MACROTETRALIDES. actin-based motility See DYSENTERY (1a) and LISTERIOSIS. Actinichona See HYPOSTOMATIA. a-actinin See ACTIN. b-actinin See ACTIN. actino- Prefix signifying a ray or rays. actinobacillosis Any animal (or human) disease caused by a species of Actinobacillus. A. lignieresii causes granulomatous lesions in and around the mouth – particularly the tongue (‘wooden tongue’) – in cattle; in sheep A. lignieresii is associated with suppurative lesions in the skin and internal organs. A. equuli is pathogenic for horses (see SLEEPY FOAL DISEASE) and pigs; in pigs symptoms may include fever, haemorrhagic or necrotic skin lesions, arthritis and endocarditis. A. suis causes septicaemia and localized lesions in pigs. (See also PERIODONTITIS.) Actinobacillus A genus of Gram-negative bacteria of the PASTEURELLACEAE. Cells: mostly rod-shaped (ca. 0.3–0.5 × 0.6–1.4 µm), but a coccal form often occurs at the end of a rod, giving a characteristic ‘Morse code’ form; filaments may occur in media containing glucose or maltose. Extracellular slime is often produced. Cells stain irregularly. Glucose, fructose, xylose, and (most strains) lactose are fermented (no gas). Growth occurs only on complex media; all species (except A. actinomycetemcomitans) can grow on MacConkey’s agar. Most species are non-haemolytic, but A. suis and some strains of A. equuli exhibit clear haemolysis on sheep blood agar; A. suis causes partial haemolysis on horse blood agar. GC%: 40–43. Type species: A. lignieresii. Actinobacilli occur as commensals in the alimentary, respiratory and/or genital tracts of animals: A. lignieresii in cattle and sheep, A. equuli in horses, A. suis in pigs(?) and horses, A. capsulatus in rabbits(?), A. actinomycetemcomitans in man. All can be opportunist pathogens (see ACTINOBACILLOSIS). (A. muris = Streptobacillus moniliformis; A. mallei = Pseudomonas mallei; A. ureae: see PASTEURELLA.) [Book ref. 22, pp. 570–575; proposal to re-classify A. actinomycetemcomitans as Haemophilus actinomycetemcomitans: IJSB (1985) 35 337–341.] Actinobifida An obsolete genus of actinomycetes which included species with dichotomously-branching sporophores; at least some strains were transferred to THERMOMONOSPORA. Actinobolina A genus of carnivorous ciliates (subclass GYMNOSTOMATIA). Cells: roughly ovoid, with uniform somatic ciliature, an apical cytostome, TOXICYSTS, and retractable tentacles distributed evenly over the body. Actinocephalus See GREGARINASINA. actinoidin See VANCOMYCIN.

4

(1)

ACRIDINE. The numbering system used in this dictionary is indicated by the numbers which are not in parentheses; an alternative numbering system (numbers in parentheses) is used by some authors.

acriflavine (acriflavin; syn. euflavin) 3,6-Diamino-10-methylacridinium chloride or (according to some authors) a mixture of this compound and 3,6-diaminoacridine (proflavine). Acriflavine is soluble in water and in ethanol, and has been used as an ANTISEPTIC. (See also ACRIDINES.) acro- Prefix meaning tip or outermost part. Acrocordia See PYRENULALES. acrolein (CH2 =CH−CHO) An aldehyde used e.g. for preFIXATION; it penetrates tissues more rapidly than GLUTARALDEHYDE. acronematic Refers to a eukaryotic FLAGELLUM which is smooth and tapers to a fine point. acropetal development Development from the base, or point of attachment, towards the tip; e.g., in a chain of acropetally developing spores the first-formed spores occupy positions in the chain nearest the base of the spore-bearing structure, while spores formed later occupy positions in the distal parts of the chain. (cf. BASIPETAL DEVELOPMENT.) acropleurogenous Located both at the tip and on the sides of an elongated structure. Acrosiphonia A genus of branched, filamentous, siphonocladous green algae (division CHLOROPHYTA). Acrospermum See CLAVICIPITALES. acrylate pathway See PROPIONIC ACID FERMENTATION. ActA protein (Listeria monocytogenes) See LISTERIOSIS. actaplanin See VANCOMYCIN. Actidione Syn. CYCLOHEXIMIDE. actin (1) A protein, found in most types of eukaryotic cell, which can polymerize (reversibly) to form non-contractile filaments (microfilaments) that are involved e.g. in maintaining cell shape and structure (see e.g. CYTOSKELETON) and (together with MYOSIN) in CAPPING (sense 3), amoeboid movement (see PSEUDOPODIUM), CYTOPLASMIC STREAMING, PHAGOCYTOSIS, and (in higher animals) muscle contraction. Actins from various sources are similar in structure. The monomeric form (G-actin) is a globular protein (MWt ca. 42000) consisting of ca. 375 amino acid residues; each molecule can bind one molecule of ATP. In most non-muscle cells, G-actin occurs in dynamic equilibrium with the polymerized (filamentous) form, F-actin, which consists of a helical, doublestranded chain of monomers ca. 7 nm thick. Although F-actin is itself non-contractile, its interaction with myosin can cause microfilaments to slide relative to one another – thereby bringing about movements and contractions in structures bound to the microfilaments. During the polymerization of G-actin ATP is hydrolysed; as in the assembly of MICROTUBULES, energy is not essential for – but increases the rate of – polymerization. Polymerization and depolymerization can occur at both ends of a microfilament, but one of the ends may grow (or depolymerize) at a greater rate than the other. (See also CAPPING sense 2.) 7

Actinomadura Actinomadura A genus of bacteria (order ACTINOMYCETALES, wall type III; group: maduromycetes) which occur e.g. in soil; some species (A. madurae, A. pelletieri ) can be pathogenic in man (see MADUROMYCOSIS). The organisms form a branching, usually stable, substrate mycelium, but (spore-forming) aerial mycelium may be common or rare according to species; some species contain only trace amounts of madurose, or none at all. GC%: reported to be within the range 65–78. Type species: A. madurae. [Taxonomic studies on Actinomadura and Nocardiopsis: JGM (1983) 129 3433–3446; ecology, isolation and cultivation: Book ref. 46, pp. 2103–2117.] Actinomucor See MUCORALES. Actinomyces A genus of asporogenous bacteria (order ACTINOMYCETALES; wall type varies with species); species occur in warm-blooded animals e.g. as part of the microflora of the mucous membranes (particularly in the mouth) and can act as opportunist pathogens. The organisms occur as rods, branched rods or filaments, or as a rudimentary mycelium. All species can grow anaerobically, or under reduced partial pressure of oxygen; growth in vitro occurs readily on rich media at 37° C, and is typically enhanced if the partial pressure of carbon dioxide is increased. Carbohydrates are fermented anaerogenically – acetic, lactic and succinic acids being the main acidic end products of glucose fermentation in PYG MEDIUM. Most species are catalase-negative; A. viscosus is catalase-positive. GC%: ca. 57–73. Type species: A. bovis. A. bovis (wall type VI) and A. israelii (wall type V) can cause chronic disease in animals and man (see ACTINOMYCOSIS); A. naeslundii and A. viscosus (both wall type V) can cause periodontitis e.g. in rodents. (See also COAGGREGATION.) A. pyogenes (formerly Corynebacterium pyogenes [JGM (1982) 128 901–903]) is the cause of ‘summer mastitis’ in cattle, and is often isolated from pyogenic lesions in cattle, pigs and other animals; A. pyogenes typically occurs as short rods or coryneforms which secrete a soluble haemolysin. A. hordeovulneris [IJSB (1984) 34 439–443] is a causal agent of actinomycosis in dogs. Actinomycetales An order of GRAM TYPE-positive, typically aerobic bacteria; species range from those which occur as cocci and/or rods to those which form a well-developed, branching SUBSTRATE MYCELIUM and/or AERIAL MYCELIUM, and which may form sophisticated structures such as sclerotia, sporangia and synnemata. (cf. ACTINOMYCETE.) Most members of the order have a GC%>55, thus distinguishing them from species of the other major subbranch of Gram-positive bacteria: the Clostridium–Bacillus–Thermoactinomyces line (but cf. CORYNEBACTERIUM, RENIBACTERIUM and THERMOACTINOMYCES). Phylogenetic relationships between actinomycetes are indicated by 16S rRNA oligonucleotide cataloguing and nucleic acid hybridization; within the order, groups of genera can be distinguished on the basis of e.g. the chemical nature of the cell wall and the lipid profiles of the organisms. [The system of classification adopted in the Dictionary is based on the scheme proposed in Book ref. 73, pp. 7–164.] Actinomycetes are widespread in nature, occurring typically in soil, composts (see COMPOSTING) and aquatic habitats; most species are free-living and saprotrophic, but some form symbiotic associations (see e.g. ACTINORRHIZA) and others are pathogenic in man, other animals, and plants (see e.g. ACTINOMYCOSIS, DERMATOPHILOSIS, JOHNE’S DISEASE, POTATO SCAB, and TUBERCULOSIS). The organisms are chemoorganotrophs; collectively they can degrade a wide range of substances which include e.g. agar, cellulose, chitin, keratin, paraffins and rubber. Some species produce important antibiotics (see e.g. STREPTOMYCES).

Ultrastructure and staining. The cell structure is that of a Gram-positive prokaryote; most species give an unequivocally positive reaction in the Gram stain (but see e.g. CELLULOMONAS), and some species are acid-fast (see e.g. MYCOBACTERIUM, NOCARDIA, RHODOCOCCUS). Cytoplasmic inclusions observed in at least some species include e.g. granules of poly-b-hydroxybutyrate, polyphosphate, and polysaccharide, and globules of lipid. The cell wall commonly appears to be either uniformly electrondense or three-layered, the electron-density of the middle layer being somewhat less than that of the layer on either side of it. The wall contains PEPTIDOGLYCAN and other polymers, e.g. TEICHOIC ACIDS – although the latter appear not to occur in the NOCARDIOFORM ACTINOMYCETES; the cell wall is commonly surrounded by a layer of diffuse or (in sporoactinomycetes) fibrous material. Depending on the presence of certain amino acids in the peptidoglycan, and the identity of the cell wall sugars, eight wall types (chemotypes I–VIII) of actinomycetes can be distinguished [Book ref. 46, pp. 1915–1922]: I. LL-DAP (LL-diaminopimelic acid), glycine. II. meso-DAP, glycine. III. meso-DAP. IV. meso-DAP, arabinose, galactose. V. Lysine, ornithine. VI. Lysine; aspartic acid and galactose sometimes present. VII. DAB (2,4-diaminobutyric acid), glycine; lysine sometimes present. VIII. Ornithine. A further wall type (IX), characterized by meso-DAP and numerous amino acids, was defined for species of MYCOPLANA. In most species which form non-fragmenting mycelium (e.g. Streptomyces spp) the vegetative hyphae are largely aseptate, although septa (cross-walls) can be present – particularly in the older parts of the mycelium. The septa in non-fragmenting mycelium have been designated type 1 septa; each septum consists of a single layer which develops centripetally from the cell wall. Such septa may contain microplasmodesmata, each 4–10 nm in diameter. In fragmenting mycelium each septum consists of two distinct layers, each layer eventually forming a terminal wall of one of the two neighbouring cells; such septa are designated type 2 septa. Spore formation. Spores are formed by the septation and fragmentation of hyphae, the spore wall being formed, at least in part, from all the wall layers of the sporogenous hypha. Spore-delimiting septa are of various types, and different types may occur even within a given genus; such septa have been designated type I (two layers developing centripetally), type II (two layers which develop centripetally on a single, initially-formed annulus), and type III (a single, thick layer which develops centripetally). Spore chains are reported to develop acropetally (in e.g. Pseudonocardia), basipetally (in e.g. Micropolyspora), randomly (in e.g. Nocardiopsis), or more or less simultaneously (in e.g. Streptomyces). In some actinomycetes the spores are formed within sporangia: see e.g. ACTINOPLANES, AMORPHOSPORANGIUM, AMPULLARIELLA, DACTYLOSPORANGIUM, FRANKIA and PILIMELIA. Genetic aspects. Genetic exchange has been studied in various actinomycetes, particularly Streptomyces spp [Streptomyces genetics: Book ref. 73, pp. 229–286; genetics of nocardioform actinomycetes: Book ref. 73, pp. 201–228]. Actinomycetes are hosts to a number of ACTINOPHAGES, and generalized transduction with phage fSV1 has been recorded in strains of Streptomyces [JGM (1979) 110 479–482]. Actinomycetes can contain various transmissible or non-transmissible plasmids, some of which 8

Actinosphaerium are involved in antibiotic production. Genetic analyses have been carried out by methods involving e.g. conjugation and protoplast fusion. Genera include: ACTINOMADURA, ACTINOMYCES, ACTINOPLANES, ACTINOPOLYSPORA, ACTINOSYNNEMA, AGROMYCES, AMORPHOSPORANGIUM, AMPULLARIELLA, ARACHNIA, ARCANOBACTERIUM, ARTHROBACTER, BREVIBACTERIUM, CASEOBACTER, CELLULOMONAS, CORYNEBACTERIUM, CURTOBACTERIUM, DACTYLOSPORANGIUM, DERMATOPHILUS, EXCELLOSPORA, FRANKIA, GEODERMATOPHILUS, INTRASPORANGIUM, KINEOSPORIA, MICROBACTERIUM, MICROBISPORA, MICROMONOSPORA, MICROPOLYSPORA, MICROTETRASPORA, MYCOBACTERIUM, NOCARDIA, NOCARDIOIDES, NOCARDIOPSIS, OERSKOVIA, PILIMELIA, PLANOBISPORA, PLANOMONOSPORA, PROMICROMONOSPORA, PSEUDONOCARDIA, RENIBACTERIUM, RHODOCOCCUS, ROTHIA, SACCHAROMONOSPORA, SACCHAROPOLYSPORA, SPIRILLOSPORA, SPORICHTHYA, STREPTOALLOTEICHUS, STREPTOMYCES, STREPTOSPORANGIUM, STREPTOVERTICILLIUM, THERMOMONOSPORA. [Ecology, isolation, cultivation etc: Book ref. 46, pp. 1915– 2123.] actinomycete Any member of the order ACTINOMYCETALES; the name is often used to refer specifically to those species which form mycelium, i.e. excluding many members of the NOCARDIOFORM ACTINOMYCETES. actinomycetoma See MADUROMYCOSIS. actinomycin D (actinomycin C1 ) An ANTIBIOTIC from Streptomyces sp; it contains a (red) substituted phenoxazone chromophore linked to two identical pentapeptide lactone rings. All cell types are potentially susceptible, any resistance being due to low permeability of cells to the drug. Actinomycin D specifically inhibits DNA-directed RNA synthesis. It binds specifically to B-DNA as an INTERCALATING AGENT (f ca. 26° ). The phenoxazone chromophore intercalates primarily between two adjacent (antiparallel) GC pairs, while the lactone rings fit into the minor groove [ARB (1981) 50 171–172]. The drug dissociates from DNA only very slowly; it blocks the movement of RNA polymerase along its DNA template. (Since actinomycin D shows little binding to AT-rich PROMOTERS chain initiation is not inhibited.) DNA replication may be insensitive to actinomycin D because strand separation by the replicative apparatus may facilitate dissociation of the antibiotic. actinomycosis (1) Any human or animal disease caused by a species of ACTINOMYCES: A. israelii in man, A. bovis in cattle. Infection is probably endogenous. Dense nodular lesions are formed, mainly around the jaw (‘lumpy jaw’), developing into pus-discharging abscesses. Abscesses may also occur in the lungs, brain or intestine. Lab. diagnosis: the pathogen may be isolated from small yellow granules (‘sulphur granules’) present in the pus. Chemotherapy: e.g. penicillins. (2) Any human or animal disease caused by an ACTINOMYCETE: e.g. actinomycosis (sense 1); MADUROMYCOSIS. (See also LACHRYMAL CANALICULITIS.) actinophage Any BACTERIOPHAGE whose host(s) are member(s) of the ACTINOMYCETALES. Actinophages, which include both temperate and virulent types, can be isolated from e.g. soils and composts; most have a wide host range, but some (e.g. BACTERIOPHAGE fEC, BACTERIOPHAGE VP5) can infect only one or a few species. (See also STYLOVIRIDAE). [Soil actinophages which lyse Streptomyces spp: JGM (1984) 130 2639–2649.] Actinophryida An order of protozoa (class HELIOZOEA) in which the cells have no skeleton and no centroplast (cf. CENTROHELIDA). Some members have flagellated stages. Sexual processes have been observed in some species. Genera include e.g. ACTINOPHRYS, ACTINOSPHAERIUM, Ciliophrys.

Actinophrys A genus of heliozoa (order ACTINOPHRYIDA). A. sol is common among vegetation in freshwater ponds and lakes. The cell is ca. 40–50 µm diam., with a highly vacuolated cytoplasm; the distinction between ectoplasm and endoplasm is not clear in living cells (cf. ACTINOSPHAERIUM). The axial filaments of the axopodia (see AXOPODIUM) originate close to the single central nucleus. Reproduction occurs asexually by binary fission. Autogamy occurs when environmental conditions are unfavourable: meiosis follows encystment of the uninucleate cell, 2–4 gametes being formed; fusion of gametes results in the formation of zygotes which can remain dormant in the cyst until conditions improve. Actinoplanes A genus of aerobic, sporogenous bacteria (order ACTINOMYCETALES, wall type II) which occur e.g. in soil, plant litter and aquatic habitats. The organisms form a branching surface mycelium, hyphal diameter ca. 0.2–1.5 µm, which may also ramify into the substratum; the mycelium later forms vertical hyphae, each developing, at its tip, a (commonly spherical) desiccation-resistant sporangium containing a number of spherical or oval spores – each bearing a polar tuft of flagella. Colonies may be e.g. yellow, orange, red, blue, brown or purple. Type species: A. philippinensis. [Morphology, ecology, isolation: Book ref. 46, 2004–2010; isolation: JAB (1982) 52 209–218.] Actinopoda A superclass of protozoa (subphylum SARCODINA) which are typically more or less spherical, typically have axopodia (filopodia in some members), and are usually planktonic. Classes: ACANTHAREA, HELIOZOEA, Phaeodarea and Polycystinea (see RADIOLARIA). Actinopolyspora A genus of bacteria (order ACTINOMYCETALES, wall type IV); the sole species, A. halophila, was isolated from a salt-rich bacteriological medium. The organisms form substrate and aerial mycelium, the latter giving rise to chains of spores; at least 10% (w/v) sodium chloride is required for growth, the optimum being ca. 15–20%, and the maximum ca. 30%. GC%: ca. 64. Type species: A. halophila. [Book ref. 73, 122–123.] Actinopycnidium See STREPTOMYCES. actinorrhiza A bacterium–plant root association in which nitrogen-fixing root nodules are formed in certain non-leguminous angiosperms infected (through root hairs) by FRANKIA strains; the plants involved are typically woody pioneers of nutrient-poor soils in cold or temperate regions in the northern hemisphere. There are at least two morphological types of actinorrhizal root nodule. In the Alnus type, formed in Alnus spp (alder) and many other plants, the root nodules are coralloid (i.e., thickened and dichotomously branched). In the Myrica type, formed e.g. in species of Myrica, Casuarina and Rubus, the nodule is clothed with upward-growing (negatively geotropic) rootlets which may aid aeration in boggy habitats. In either type, the endophyte occurs within the cortical parenchyma of the nodule and does not invade vascular or meristematic tissues. In the distal part of the nodule the (young) hyphae spread from cell to cell, perforating the host cell walls. In the proximal part the hyphal tips swell to form vesicles which appear to provide a reducing environment within which NITROGEN FIXATION can occur; rates of nitrogen fixation are comparable to those in leguminous ROOT NODULES. [Book ref. 55, pp. 205–223.] (See also MYCORRHIZA.) Actinosphaerium A genus of heliozoa (order ACTINOPHRYIDA) in which the cells are multinucleate and ca. 200 µm to 1.0 mm in diameter, according to species; the highly vacuolated ectoplasm is clearly distinct from the granular endoplasm (cf. ACTINOPHRYS). Numerous needle-like axopodia radiate from the 9

Actinosporangium acute-phase proteins Various types of protein, found in plasma, formed as a rapid response to infection; they are synthesized in the liver e.g. under stimulation from cytokines produced in a region of INFLAMMATION. These proteins include C-REACTIVE PROTEIN (CRP) and serum amyloid A (SAA), both of which can bind to phospholipids in the microbial cell envelope and act as OPSONINS; additionally, binding by CRP activates COMPLEMENT. CRP and SAA are so-called pentraxin proteins in which the molecule consists of five identical subunits. (See also CD14.) acute-phase serum Serum obtained from a patient during the acute phase of a disease. acute respiratory disease See ARD. ACV ACYCLOVIR. ACVs See VACCINE. acycloguanosine Syn. ACYCLOVIR. acyclovir (ACV; acycloguanosine; Zovirax) An ANTIVIRAL AGENT, 9-(2-hydroxyethoxymethyl)guanine, which is active against alphaherpesviruses. It is phosphorylated by the virus-encoded thymidine kinase to the monophosphate; the monophosphate is converted by host-cell enzymes to the active triphosphate form which inhibits DNA polymerase – the viral polymerase being much more sensitive than the cellular a-polymerase. (cf. BROMOVINYLDEOXYURIDINE.) Uninfected cells do not effectively phosphorylate acyclovir, and the drug is relatively non-toxic to the host. Acyclovir is used topically, systemically or orally in the treatment of e.g. herpes simplex keratitis, primary genital herpes, mucocutaneous herpes simplex in immunocompromised patients, progressive varicella and HERPES ZOSTER. Acyclovir is not equally active against all alphaherpesviruses – its ability to inhibit the replication of varicella-zoster virus is approximately 10-fold lower than its ability to inhibit replication of herpes simplex virus. [Use of acyclovir in the treatment of herpes zoster: RMM (1995) 6 165–174 (167–170).] acylalanine antifungal agents See PHENYLAMIDE ANTIFUNGAL AGENTS. N-acyl-L-homoserine lactone See QUORUM SENSING. Acytostelium A genus of cellular slime moulds (class DICTYOSTELIOMYCETES) in which the sorocarp stalk is acellular, cellulosic, slender, and apparently tubular; no myxamoebae are sacrificed in stalk formation (cf. DICTYOSTELIUM). The stalk bears a single terminal sorus of spores. Four species are recognized [descriptions and key: Book ref. 144, pp. 393–407]. Ad Human adenovirus: see MASTADENOVIRUS. A–D group ALKALESCENS–DISPAR GROUP. ADA deficiency See ADENOSINE DEAMINASE DEFICIENCY. ada gene See ADAPTIVE RESPONSE. adamantanamine See AMANTADINE. adamantane See AMANTADINE. Adansonian taxonomy A method of biological classification, proposed in the 18th century by Michel Adanson, in which relationships between organisms are defined by the number of characteristics which the organisms have in common; the same degree of importance (‘weighting’) is attached to each characteristic. (cf. NUMERICAL TAXONOMY.) adaptation Change(s) in an organism, or population of organisms, by means of which the organism(s) become more suited to prevailing environmental conditions. Genetic adaptation involves e.g. mutation and selection: those (mutant) organisms in a given population which are genetically more suited to the existing environment thrive and become numerically dominant. (See also FLUCTUATION TEST.) Non-genetic (phenotypic) adaptation

cell, their axial filaments arising at the junction between ectoplasm and endoplasm. Asexual reproduction involves plasmotomy. Autogamy occurs when environmental conditions become unfavourable: the cell produces a gelatinous covering, and many of its nuclei degenerate; numerous uninucleate daughter cells are produced, and each encysts. Meiosis within the cyst results in two haploid gametes which fuse, and the resulting zygote remains dormant until conditions improve. Actinosporangium See STREPTOMYCES. Actinosporea A class of protozoa (phylum MYXOZOA) which are parasitic in invertebrates (particularly annelid worms). The spores contain 3 polar capsules (each enclosing a single polar filament) and several to many sporoplasms. The spore wall consists of 3 valves which may be smooth (e.g. in Sphaeractinomyxon) or drawn out into long, horn-like processes (as in Triactinomyxon, a parasite of tubificid and sipunculid worms). (cf. WHIRLING DISEASE.) Actinosynnema A genus of bacteria (order ACTINOMYCETALES, wall type III) which occur e.g. on vegetable matter in aquatic habitats. The organisms form a thin, branching, yellow substrate mycelium (hyphae 100° C and then cooled; gelling occurs at ca. 40–45° C. 16

(a)

(b)

adaptor

restriction fragment

adaptor

5′−AATTGNNNNNNN−3′

NNNG−3′

CNNNNNNN−5′

NNNCTTAA−5′

(c)

NNNGAATTGNNNNNNN−3′ NNNCTTAACNNNNNNN−5′

(d)

NNNGAATTGNNNNNNN−3′ TCTTAACNNNNNNN−5′

primer

AFLP FINGERPRINTING (principle, diagrammatic). Chromosomes of the test strain are initially digested with two types of RESTRICTION ENDONUCLEASE, commonly EcoRI (recognition site: G/AATTC) and MseI (recognition site: T/TAA). As a result, the two sticky ends of each fragment may be created either by the same enzyme or by different enzymes. The chromosomal fragments are then mixed with ‘adaptor’ molecules of two types, here designated A and B. Each type of adaptor molecule is a short DNA sequence which has one sticky end that corresponds to the recognition sequence of one of the two restriction enzymes. The reaction mixture contains a ligase, so that covalent binding between fragments and adaptor molecules gives rise to the following sequences: A-fragment-A, A-fragment-B, B-fragment-A and B-fragment-B. Note. In each adaptor molecule a ‘mutant’ nucleotide is incorporated immediately adjacent to the sticky end so that, after ligation to a fragment, the cutting site of the enzyme is not restored; thus, following ligation, the sequence is not susceptible to restriction. The fragments, flanked on each side by (ligated) adaptor molecules, are now subjected to PCR under high-stringency conditions. Each PCR primer is designed to be complementary to one or other of the adaptor molecules, including the restriction site; however, an important feature of each primer is that its 3′ end extends for one or a few nucleotides beyond the restriction site – i.e. into the ‘unknown’ fragment. The one (or few) 3′ nucleotide(s) of the primer are selective nucleotides, i.e. the primer will be extended only if these nucleotides are paired with complementary nucleotides in the fragment. Hence, while primers may bind to all fragments in the mixture, only a subset of fragments will be amplified, i.e. those fragments containing nucleotides that are complementary to the selective 3′ nucleotide(s) of the primer. A primer with one selective nucleotide has a 1-in-4 chance of binding to a complementary nucleotide in the fragment; this type of primer will amplify only about one in four of the fragments to which it binds. The primers of one type are labelled so that, following PCR and gel electrophoresis of the products, a fingerprint of (e.g. ∼50–200) detectable bands is obtained. (a) Each restriction fragment is flanked by (ligated) adaptor molecules. (b) Left. A fragment’s sticky end produced by EcoRI (N = nucleotide). Right. An adaptor molecule with the complementary 5′ -AATT overhang; note that, in the overhang strand, the 5′ -AATT is followed by G, rather than C. (c) Following base-pairing of the sticky ends in (b), and ligation, the resulting sequence 5′ -GAATTG-3′ 3′ -CTTAAC-5′ differs from the cutting site of EcoRI and is not susceptible to cleavage by EcoRI. (d) During cycling, a primer binds to one strand of the fragment–adaptor junction region. As this primer’s 3′ -terminal (selective) nucleotide is T, the primer will be extended only if the complementary nucleotide (A) occurs at this location in the fragment; extension will not occur on this fragment if T is mis-matched. Reproduced from Figure 7.6, page 193, in DNA Methods in Clinical Microbiology (ISBN 07923-6307-8), Paul Singleton (2000), with kind permission from Kluwer Academic Publishers, Dordrecht, The Netherlands.

17

agar diffusion test Cortinariaceae. Basidiocarp: stipitate, characteristically with a fine, cobweb-like cortina; basidiospores: rust-coloured or some shade of brown, smooth to rough. Genera include Cortinarius, Galerina, Inocybe (see also MUSCARINE). Crepidotaceae. Basidiocarp: non-stipitate, or with a rudimentary lateral stipe; basidiospores: cinnamon-coloured. Genera include CREPIDOTUS. Hygrophoraceae (‘wax caps’). Basidiocarp: stipitate, often brightly coloured, the lamellae being waxy, and the basidia typically elongated; basidiospores: colourless. Genera include Hygrocybe and Hygrophorus. Pluteaceae. Basidiocarp: stipitate with a volva, the lamellae each having a convergent BILATERAL TRAMA; basidiospores: pink. Genera include Volvariella (see also PADI-STRAW MUSHROOM). Strophariaceae. Basidiocarp: stipitate (stipe often elongated), pileus e.g. buff, yellow, ochre, or (in Stropharia aeruginosa) greenish; basidiospores: typically brown to purplish-brown. Genera include Hypholoma, Panaeolus, Pholiota, Psilocybe, Stropharia. (See also HALLUCINOGENIC MUSHROOMS.) Tricholomataceae. Basidiocarp: stipitate, lamellae with nonbilateral trama; basidiospores: white or pink, without a germ pore. Genera include ARMILLARIA, Clitocybe, Collybia, Crinipellis (see also WITCHES’ BROOM), Flammulina (see also ENOKITAKE), LENTINULA, LEPISTA, Marasmius (see also MYCORRHIZA), Mycena (see also BIOLUMINESCENCE), Omphalotus, Oudemansiella, Tricholoma. agaricoid Refers to the type of fruiting body which is characteristic of fungi of the AGARICALES: gymnocarpic, with the hymenium forming a layer on lamellae and giving rise to ballistospores. (cf. GASTEROID.) Agaricus (formerly Psalliota) A genus of fungi (AGARICALES, Agaricaceae), most (not all) species of which are edible. Except in A. brunnescens, the basidia each form four basidiospores; basidiospores are dark brown and commonly ovoid. A. arvensis is the horse mushroom, A. campestris the common or field mushroom, and A. silvicola the wood mushroom (all edible species). A brunnescens (= A. bisporus), a species which forms two-spored basidia, is the cultivated mushroom (see MUSHROOM CULTIVATION). (See also FUNGUS GARDENS.) agarobiose A disaccharide: 3,6-anhydro-4-O-(b-D-galactopyranosyl)-L-galactose, a degradation product of AGAR. agaropectin See AGAR. agarophyte (agarphyte) Any AGAR-producing seaweed. agarose See AGAR. age-dependent polioencephalomyelitis (in mice) See LACTATE DEHYDROGENASE VIRUS. agglutinated test (protozool.) See e.g. FORAMINIFERIDA. agglutination The formation of insoluble aggregates following the combination of antibodies with cells or other particulate antigens (see e.g. WEIL–FELIX TEST) or with soluble antigens bound to cells or other particles (see e.g. LATEX PARTICLE TEST), or following the combination of soluble (or particulate) antigens with cell-bound or particle-bound antibodies (see e.g. PROTEIN A); agglutination may also be mediated by e.g. LECTINS or by fibrinogen (see clumping factor in COAGULASE). Agglutination may be detected macroscopically as suspended aggregates or (subsequently) as sedimented aggregates. (See also PASSIVE AGGLUTINATION and HAEMAGGLUTINATION; cf. PRECIPITATION and FLOCCULATION sense 1.) On sedimentation, agglutinated particles may form a mat over a relatively large area of the bottom of the test-tube; by contrast, non-agglutinated particles generally sediment to form a smaller, dense button in the control tube.

Media made from Japanese agars usually contain 1.5–2.0% w/v agar; however, semi-solid agars contain 0.5% or less, and stiff agars contain e.g. 8% w/v. (If New Zealand agars are used, these concentrations should be halved to give gels of similar strengths.) Sterile gels are prepared by autoclaving a suspension of agar in water (see AUTOCLAVE). Growth media are prepared by adding nutrients, selective agents etc to the agar – usually before autoclaving but sometimes after (see e.g. BLOOD AGAR). If the medium is to have a pH of 6.0 or less, the pH must be adjusted after autoclaving, since agar is hydrolysed during heating at low pH. Various refined forms of agar may be used for specific purposes: e.g. ion-free agar may be used in immunoelectrophoresis. (See also ELECTROENDOSMOSIS.) Agar is a useful base for microbiological media in that it gels at moderate temperatures and, once set, the gels are stable at temperatures up to ca. 65° C or higher (although syneresis tends to occur at these temperatures); furthermore, the ability to degrade agar is confined to only a few organisms (including e.g. strains of Streptomyces coelicolor, certain marine pseudomonads, marine species of Cytophaga). (cf. GELATIN.) However, agar shortages, product variability, and rising prices have led to a search for suitable substitutes for agar; substitutes which have found some applications include CARRAGEENAN, Gelrite (see GELLAN GUM), low-methoxy PECTINS, and SILICA GELS. agar diffusion test A DIFFUSION TEST which differs from the DISC DIFFUSION TEST in that, instead of employing antibioticimpregnated discs, a solution of each antibiotic is allowed to diffuse from a separate ‘well’ cut into the agar. agar dilution test See DILUTION TEST. agar disc diffusion test Syn. DISC DIFFUSION TEST. agar gel diffusion See GEL DIFFUSION. agar plate See PLATE. agar-slide method Syn. DIP-SLIDE METHOD. agaric (1) Any fungus of the Agaricaceae. (2) Any fungus of the AGARICALES. (3) Any fungus whose hymenium is borne on lamellae (see LAMELLA). Agaricaceae See AGARICALES. Agaricales An order of terrestrial (typically humicolous or lignicolous), mainly saprotrophic fungi (subclass HOLOBASIDIOMYCETIDAE) most of which form mushroom-shaped, gymnocarpic or semiangiocarpic, fleshy fruiting bodies in which the hymenium is borne on radially arranged ‘gills’ (= lamellae, see LAMELLA) on the underside of the pileus; the pileus and (when present) stipe do not contain sphaerocysts (cf. RUSSULALES). (See also SECOTIOID FUNGI.) The order may be divided into families on the basis of e.g. basidiospore colour, the structure of the trama, and the nature of the cortical layers of the pileus [Book ref. 64, pp. 7–8]; these families include: Agaricaceae. Basidiocarp: stipitate, typically with an annulus when mature; basidiospores: typically dark brown or colourless, but not rust- or cinnamon-coloured. Genera include AGARICUS and LEPIOTA. Amanitaceae. Basidiocarp: stipitate, the lamellae each having a divergent BILATERAL TRAMA; basidiospores: white or pale. Some species form both a PARTIAL VEIL and a UNIVERSAL VEIL. Genera include AMANITA (volva formed), Limacella (volva not formed), and TERMITOMYCES. Bolbitiaceae. Basidiocarp: stipitate; basidiospores: ochre or cinnamon to rust-brown. Genera include Agrocybe and Conocybe. Coprinaceae. Basidiocarp: stipitate, a palisade-like layer of cells occurring in the pellis; basidiospores: dark or black, each usually containing a germ pore. Genera include COPRINUS and Psathyrella. 18

AHG Agrobacterium spp occur in soil, mainly in the rhizosphere. All (except A. radiobacter) can infect a wide range of dicotyledonous plants (and some gymnosperms) and induce the formation of self-proliferating galls or adventitious roots. The species are defined primarily or solely on the basis of their pathogenic characteristics: A. radiobacter is non-pathogenic, A. rhizogenes causes HAIRY ROOT, A. rubi causes CANE GALL, and A. tumefaciens causes CROWN GALL. However, pathogenicity depends on the presence of a plasmid(s) and can readily be altered or lost; hence the currently recognized species do not reflect true taxonomic relationships among the agrobacteria. [Book ref. 22, pp. 244–254.] [Media and culture: Book ref. 45, 842–855.] agrocin 84 See AGROCINS. agrocinopines A class of (sugar phosphodiester) opines found in CROWN GALL. (See also AGROCINS.) agrocins Antibiotics which are produced by certain strains of Agrobacterium and which are active against other strains of the same genus; being non-protein in structure, agrocins are not strictly BACTERIOCINS. Agrocin 84 is produced by a nonpathogenic, nopaline-catabolizing strain of A. radiobacter (strain 84, NCPPB 2407) and is selectively active against agrobacteria which harbour a nopaline Ti plasmid. Strain 84 is used in the BIOLOGICAL CONTROL of CROWN GALL; a cell suspension is used to treat seeds, roots or wounded plant surfaces (e.g. graft wounds), and almost 100% control of nopaline pathogens (responsible for most of the economic damage due to crown gall) can be achieved. Agrocin 84 is an adenine nucleotide derivative containing an N 6 -phosphoramidate substituent (necessary for uptake by sensitive cells) and a 5′ -phosphoramidate substituent (necessary for toxicity). Agrocin 84 is taken up by sensitive strains via a high-affinity ‘agrocin permease’, apparently an agrocinopine transport system normally inducible by agrocinopines (sugar phosphodiesters) present in galls caused by nopaline strains. Strain 84 contains at least three plasmids: one (pAgK84, 47.7 kb) coding for agrocin 84 production, another (pAt84b, ca. 200 kb) coding for nopaline catabolism. pAgK84 is self-transmissible only at very low frequencies, but can be mobilized by the conjugative plasmid pAt84b. As transfer of pAgK84 to a crown gall pathogen could threaten the continued use of agrocin 84 in biocontrol, a transfer-deficient mutant strain was prepared. However, strain K84 apparently exerts some activity against agrocin 84-resistant pathogens independently of pAgK84 [AEM (1999) 65 1936–1940]. Agrocybe See AGARICALES (Bolbitiaceae). agroinfection A method for introducing viral DNA (or cDNA) into a plant. Viral DNA is initially incorporated into the T-DNA part of a Ti plasmid. The plasmid is then introduced into the bacterium Agrobacterium tumefaciens–which is used to infect the plant; during infection the viral DNA is transferred to plant cells within the T-DNA (see CROWN GALL). [Example of use: JV (2003) 77 3247–3256.] Agromyces A genus of microaerophilic to anaerobic, catalasenegative, asporogenous bacteria (order ACTINOMYCETALES, wall type VII – see also PEPTIDOGLYCAN). The organisms grow as a branched mycelium which subsequently fragments into coccoid and diphtheriod forms; metabolism: oxidative. A. ramosus, the type species, occurs in large numbers in certain soils; it appears to attack and destroy other species of bacteria [AEM (1983) 46 881–888]. agropine See CROWN GALL and HAIRY ROOT. Agropyron mosaic virus See POTYVIRUSES. AHG (serol.) Anti-human globulin: ANTIGLOBULIN homologous to human globulins.

agglutination factor (algol.) See CHLAMYDOMONAS. agglutination test Any test in which reactions between particulate and/or soluble entities (particularly free or particle-bound antibodies and antigens) is detected by AGGLUTINATION. agglutinin (1) Any ANTIBODY involved in an AGGLUTINATION reaction. (2) Any substance which can agglutinate cells or inanimate particles by binding to their surface components. agglutinogen The antigen homologous to an agglutinin. Aggregata See EIMERIORINA. aggregate gold standard See GOLD STANDARD. aggregation substance See PHEROMONE. aggressin Any product or component of a pathogenic microorganism which promotes the invasiveness of that organism – see e.g. HYALURONATE LYASE. (cf. STREPTOKINASE; see also ADHESION and IGA1 PROTEASES.) aglycon The non-sugar portion of a glycoside. agmatine See e.g. DECARBOXYLASE TESTS. Agmenellum A phycological genus of ‘blue-green algae’ currently included in the SYNECHOCOCCUS complex. agnogene See AGNOPROTEIN. agnoprotein A 61-amino acid, highly basic polypeptide encoded by a gene (the ‘agnogene’) in the late leader region of SIMIAN VIRUS 40; it appears to play a role in viral assembly. Agonomycetales (Mycelia Sterilia) An order of fungi (class HYPHOMYCETES) which include species that form neither conidia nor sexual structures, though some species have been found to have teleomorphs in the Ascomycotina or the Basidiomycotina. The order includes lichenized fungi (e.g. LEPRARIA) and plant pathogens (see e.g. RHIZOCTONIA and SCLEROTIUM). agr locus (in Staphylococcus aureus) Accessory gene regulator locus: a chromosomal sequence which encodes, inter alia, (i) the sensor and response regulator of a TWO-COMPONENT REGULATORY SYSTEM (AgrA–AgrC), and (ii) an octapeptide ‘pheromone’ which is secreted by the cell and which, at appropriate concentrations (see QUORUM SENSING), activates the two-component system. When activated, the AgrA–AgrC system upregulates expression of the (agr-encoded) transcript RNA III which, in turn, regulates the expression of genes for exotoxins and certain cell-surface-associated virulence factors. Another two-component system, encoded by the srrAB genes (staphylococcal respiratory response genes), appears to regulate the expression of exotoxins and certain cell-surface virulence factors in accordance with the levels of environmental oxygen, such regulation being exerted, in part, via the agr system [JB (2001) 183 1113–1123]. agranulocyte Any white blood cell which has non-granular cytoplasm, e.g., a LYMPHOCYTE. Agrobacterium A genus of Gram-negative bacteria of the RHIZOBIACEAE. Cells: rods (0.6–1.0 × 1.5–3.0 µm), capsulated. Motile, with between one (often non-polar) and six peritrichous flagella. Optimum growth temperature: 25–28° C. Species can metabolize a wide range of mono- and disaccharides and salts of organic acids; acid (no gas) is formed from glucose (which is metabolized mainly via the ENTNER–DOUDOROFF PATHWAY and the HEXOSE MONOPHOSPHATE PATHWAY). Colonies on carbohydrate-containing media are typically mucilaginous, abundant extracellular slime (including a neutral (1 → 2)-b-glucan) being produced. (See also CURDLAN.) Some strains can use NH4 + and NO3 − as nitrogen sources, while others require amino acids; some strains can carry out NITRATE RESPIRATION. Nitrogen fixation does not occur. GC%: 57–63. Type species: A. tumefaciens. 19

AHL AHL See QUORUM SENSING. ahpC gene See ISONIAZID. AID (activation-induced cytidine deaminase) See RNA EDITING. AIDA-I In Escherichia coli: an adhesin that mediates diffuse adherence (to e.g. HeLa cells) – hence the designation adhesin involved in diffuse adherence. AIDA-I is the a domain of an autotransporter (see type IV systems in PROTEIN SECRETION); in wild-type cells the a domain is apparently cleaved (autocatalytically?), but it remains attached (non-covalently) to the cell surface. (See also AUTODISPLAY.) aidB gene See ADAPTIVE RESPONSE. AIDS (acquired immune deficiency syndrome) In an HIV+ individual (see HIV): the stage of disease characterized by (i) counts of CD4+ T LYMPHOCYTES commonly within or below the range 200–500/µl (in adults and adolescents) and (ii) the presence of one or more category C diseases (AIDS-defining diseases specified in the clinical staging system of the Centers for Disease Control (CDC), Atlanta, Georgia, USA); category C diseases include e.g. CANDIDIASIS of the lower respiratory tract; disseminated COCCIDIOIDOMYCOSIS; extrapulmonary CRYPTOCOCCOSIS; retinitis due to cytomegalovirus (BETAHERPESVIRINAE); herpes simplex oesophagitis; HIV-related encephalopathy; extrapulmonary HISTOPLASMOSIS; chronic infection with ISOSPORA; KAPOSI’S SARCOMA; primary lymphoma of the brain; extrapulmonary infection with Mycobacterium tuberculosis (see also MAC); pneumonia caused by PNEUMOCYSTIS CARINII; TOXOPLASMOSIS of the brain. [Infections in AIDS (MICROSPORIDIOSIS, invasive pneumococcal disease, non-typhoid salmonellae): JMM (2000) 49 947–957.] The normal CD4 count in adults/adolescents is ∼1000/µl; in neonates it is much higher (≥2000), so that the adultbased relationship between CD4 counts and susceptibility to opportunist pathogens is not appropriate for very young children. [AIDS Insight (various aspects): Nature (2001) 410 961– 1007.] Transmission/containment of HIV. HIV can be transmitted: (i) by sexual contact (male ↔ female, as well as homosexual); (ii) via transfusion of (infected) blood or blood products (e.g. contaminated Factor VIII formerly given to haemophiliacs); (iii) via the placenta; (iv) by breast-feeding; and (v) through use of contaminated needles by intravenous drug abusers. The highest concentration of virus (free and intracellular) is found in blood; HIV also occurs e.g. in semen, milk and cerebrospinal fluid. Efforts to prevent/limit the spread of HIV have included: (i) education (making clear the basic facts of the disease, including routes of transmission); (ii) discouraging promiscuity; (iii) encouraging the use of condoms; (iv) discouraging needlesharing by drug addicts; (v) screening of blood donors; (vi) treatment of blood products. Clinical manifestations of HIV infection. Infection is commonly followed, in ∼2–6 weeks, by an early ‘acute’ phase which is characterized by high-level viraemia; p24 antigen (the major core protein: see HIV) can often be demonstrated in serum during the viraemic phase. Levels of virus remain high for some weeks – after which there is a sharp decline (and a loss of detectable p24 antigen); this decline in viraemia appears to reflect the activity of antigen-specific CD8+ cytotoxic T cells (see T LYMPHOCYTE) and may also involve nonspecific killing of virus-infected cells by NK CELLS.

Antibodies (e.g. anti-gp120, anti-p24) are first detectable ∼6–12 weeks after infection; their appearance may follow, or coincide with, the rapid decline in viraemia. During seroconversion some patients experience a seroconversion illness which may include e.g. fever, sore throat, skin rash, generalized lymphadenopathy, pneumonitis, gastrointestinal and/or CNS involvement. A subsequent phase of infection is characterized by persistent generalized lymphadenopathy (PGL) (also called lymphadenopathy syndrome) – swollen lymph nodes reflecting an active immune response to HIV. (In some cases, PGL is the first manifestation of disease following infection, i.e. in patients who do not exhibit an acute phase.) Infection may then become asymptomatic (‘clinically latent’), and this state may continue for months or years (during which time viral replication continues). Patients with clinically latent infection, as well as those with PGL, may pass directly to AIDS. Alternatively, both types of patient may progress to AIDS via a further stage commonly referred to as the AIDS-related complex (ARC) (= category B of the CDC clinical staging system). Category B diseases include bacillary angiomatosis (see BARTONELLA), oropharyngeal candidiasis, HAIRY LEUKOPLAKIA, LISTERIOSIS, PID (pelvic inflammatory disease), herpes zoster (involving at least two distinct episodes, or more than one dermatome), and peripheral neuropathy. In AIDS, the final stage, the CD4+ count is often 56° C, by pH 8.5, and by organic solvents or detergents. Arenaviruses can replicate in a wide range of mammalian cell cultures (e.g. BHK-21, Vero and L cells). Virus replication occurs in the cell cytoplasm; the virus matures by budding through the plasma membrane, when ribosomes become incorporated in the virion. Arenavirus See ARENAVIRIDAE. areolate Divided up into small areas (areolae). (Used e.g. of a lichen thallus: see e.g. RHIZOCARPON.) arg-poly(asp) Syn. CYANOPHYCIN. arg regulon See ARGININE BIOSYNTHESIS. Argentinian haemorrhagic fever A VIRAL HAEMORRHAGIC FEVER caused by the Jun´ın virus (see ARENAVIRIDAE). Mortality: usually ca. 3–15%. argentophilic Staining well with SILVER STAINS. L-arginine biosynthesis See Appendix IV(a). In Escherichia coli the genes encoding enzymes for arginine biosynthesis constitute a REGULON (the arg regulon); four of the genes occur in a cluster (argECBH ), the remainder occur singly at loci scattered around the chromosome. [Biosynthesis and metabolism of arginine in bacteria: MR (1986) 50 314–352.] arginine decarboxylase test See DECARBOXYLASE TESTS. arginine deiminase See ARGININE DIHYDROLASE.

one at each end of the molecule; such molecules, which have two polar ends, may span the width of the cytoplasmic membrane. [Protein translocation across the archaeal cytoplasmic membrane: FEMS Reviews (2004) 28 3–24.] The archaeal flagellum is markedly different in composition, structure and apparent mode of assembly from that found in bacteria. For example, the subunit, flagellin, is typically glycosylated, and it contains a signal sequence (see SIGNAL HYPOTHESIS) – suggesting passage into/through the cytoplasmic membrane (cf. bacterial flagellin, which passes through the hollow structures of the developing flagellum); this latter feature (as well as certain similarities between archaeal flagellins and bacterial type 4 fimbriae) suggests that archaeal flagella assemble from the base (in contrast to ‘tip growth’ in bacteria) [JB (1996) 178 5057–5065]. The archaeal flagellar filament is typically much thinner than the bacterial filament. Various similar or analogous proteins have been found in archaeans and bacteria. For example, the archaeal RadA protein is apparently analogous to the RecA protein in bacteria [GD (1998) 12 1248–1253]. Again, an FtsZ protein occurs in members of both domains, suggesting that the cell division apparatus was similar in a common ancestor [Mol. Microbiol. (1996) 21 313–319]. [The CELL CYCLE in archaeans: Mol. Microbiol. (2003) 48 599–604.] archaean A member of the domain ARCHAEA. The term is also spelt ‘archaeon’. Archaebacteria A kingdom (now obsolete) which included all those prokaryotes not classified in the kingdom EUBACTERIA. [Phylogeny of the Archaebacteria: SAAM (1985) 6 251–256.] Some archaebacteria were placed in a separate taxon, Eocyta, on the basis of ribosomal characteristics [PNAS (1984) 81 3786–3790]. (See also EOCYTES.) Members of the Archaebacteria are now included in the domain ARCHAEA. Archaeobacteria A proposed class of prokaryotes (see MENDOSICUTES) corresponding to the (later) kingdom ARCHAEBACTERIA (now also obsolete). Archangium See MYXOBACTERALES. archicarp In ascomycetes: the cell(s) which give rise to a fruiting body or to a part of it. archigregarines See GREGARINASINA. Arcobacter A genus of Gram-negative, asporogenous bacteria of the family Campylobacteraceae. Cells: spiral rods with unsheathed flagella. Catalase +ve. Nitrate is reduced. Typically urease −ve. These organisms resemble Campylobacter spp but differ e.g. in their ability to grow in air at 15–25° C. A. butzleri and A. cryophilus have been isolated from patients with diarrhoea, including children in the developing countries; most strains do not hydrolyse hippurate but do hydrolyse indoxyl acetate. arcuate Curved like a bow; arched. Arcyria A genus of slime moulds (class MYXOMYCETES) which form stalked, globose to cylindrical sporangia; the peridium is evanescent, and the spores in masses may be yellow, pinkish, red, etc. A. cinerea is common on dead wood and humus. ARD Acute respiratory disease: a general term for any such disease affecting closed populations of people (e.g. military recruits, school children). Major causal agents of ARDs are adenoviruses (usually Ad3, Ad4, Ad7, Ad14, or Ad21 – see MASTADENOVIRUS); an incubation period of ca. 5–7 days is followed by fever, chills, headache, malaise and coryza, but the disease is usually mild and self-limiting. A live vaccine, administered orally in enteric-coated capsules, is widely used for preventing adenoviral ARD in military recruits. 51

arginine dihydrolase arginine dihydrolase (ADH) An enzyme system which catalyses the catabolism of arginine, with a concomitant substrate-level phosphorylation; the system occurs in a range of bacteria. (i) Arginine deiminase hydrolyses arginine to citrulline and ammonia. (ii) Ornithine carbamoyltransferase catalyses a phosphorolytic cleavage of citrulline to form carbamoyl phosphate and ornithine. (iii) Carbamate kinase transfers the phosphate group of carbamoyl phosphate to ADP to form ATP and carbamic acid, the latter dissociating spontaneously to CO2 and NH3 . Tests for ADH production are widely used in the identification of certain bacteria (e.g. members of the ENTEROBACTERIACEAE). Typically, the organism is grown in a medium containing Larginine and a pH indicator; the presence of ADH is indicated by an alkaline reaction after a few days’ incubation. [Methods: Book ref. 2, pp. 411–412.] arg-poly(asp) Syn. CYANOPHYCIN. argT gene See BINDING PROTEIN-DEPENDENT TRANSPORT SYSTEM. Argyn See SILVER. Argyrol See SILVER. argyrome Syn. SILVER LINE SYSTEM. argyrophilic Syn. ARGENTOPHILIC. arildone (4-[6-(2-chloro-4-methoxyphenoxy)-hexyl]-3,5-heptanedione) An ANTIVIRAL AGENT which is active against various DNA and RNA viruses in vitro; it blocks uncoating in polioviruses and apparently also in herpes simplex viruses. Arildone may be useful clinically e.g. in the topical treatment of HERPES SIMPLEX infections. Arizona See SALMONELLA. arizonosis A POULTRY DISEASE, caused by Salmonella arizonae (= Arizona hinshawii), characterized by malaise, diarrhoea, and often symptoms of CNS involvement. Arkansas bee virus See NODAVIRIDAE. ArlS–ArlR See TWO-COMPONENT REGULATORY SYSTEM. Armillaria (‘Armillariella’) A genus of mainly lignicolous fungi (AGARICALES, Tricholomataceae). A. mellea (the ‘honey fungus’) grows saprotrophically on many types of wood, forms a symbiotic association with certain orchids (see MYCORRHIZA), and is parasitic on a range of deciduous and coniferous trees, on certain shrubs, and on some herbaceous plants. The fruiting body is highly variable in colour and appearance, the pileus being convex to flat (ca. 3–15 cm diam.), ochre to brown, with darker scales particularly near the centre; the upper part of the stipe, which often bears a wide annulus, is initially whitish, later reddish-brown. Basidiospores: ca. 8–9 × 5–6 µm. The fruiting bodies (which exhibit BIOLUMINESCENCE) typically occur in clusters. The organism spreads by means of tough, black RHIZOMORPHS (‘boot laces’) which may be found e.g. under the bark of infected trees or in soil. (See also CARBON DISULPHIDE and THREITOL.) Armillariella See ARMILLARIA. armoured dinoflagellates See DINOFLAGELLATES. aroA gene See STAPHYLOCOCCUS (S. aureus). arogenate See AROMATIC AMINO ACID BIOSYNTHESIS. aroH gene See TRP OPERON. aroma bacteria See DIACETYL. aromatic amino acid biosynthesis Phenylalanine (Phe), tyrosine (Tyr) and tryptophan (Trp) are synthesized via the shikimate pathway: Appendix IV(f). Although most of the steps in this pathway are apparently more or less universal, the control mechanisms and physical organization of the enzymes (e.g. the formation of multienzyme complexes) vary between species and may be useful taxonomic criteria [CRM (1982) 9 227–252]. The reactions by which prephenate is converted to Phe and Tyr

also differ in different species. Thus, e.g., Escherichia coli and Bacillus subtilis synthesize Tyr via 4-hydroxyphenylpyruvate (HPP), and Phe via phenylpyruvate (PPy) [see Appendix IV(f)]. Certain cyanobacteria and ‘coryneforms’ (Corynebacterium glutamicum, Brevibacterium spp) synthesize Phe via PPy but lack prephenate dehydrogenase and synthesize Tyr via arogenate (= ‘pretyrosine’). Pseudomonas diminuta synthesizes Phe via arogenate but Tyr via HPP, while P. aeruginosa can synthesize Phe and Tyr via PPy and HPP, respectively, and also via arogenate. Euglena gracilis synthesizes both Phe and Tyr via arogenate only. (See also TRP OPERON.) aromatic hydrocarbons See HYDROCARBONS. array (DNA) See DNA CHIP. Arrhenatherum blue dwarf virus See FIJIVIRUS. Arrhenius effect See staphylococcal a-HAEMOLYSIN. Arrhenosphaera See ASCOSPHAERALES. ARS Autonomously replicating sequence: a DNA sequence (first described from the yeast Saccharomyces cerevisiae) which, when linked to a non-replicative DNA fragment, promotes the capacity for autonomous intracellular replication. ARSs occur in the yeast genome with a frequency of about one ARS for every ∼40 kilobases. Efficient replication of ARS-containing DNA fragments may require other factors such as the CEN (centromere) element and the minichromosome maintenance protein 1. Many of the ARSs appear to function as origins of replication, although some are so-called silent origins; some of the ARSs (both active and silent) are reported to act as transcription silencers. Most of the studies on ARSs have been carried out on eukaryotes–particularly on yeasts (e.g. Saccharomyces, Hansenula). However, ARSs have also been reported in prokaryotes [see e.g. JB (2003) 185 5959–5966]. arsenate respiration See SELENATE RESPIRATION. arsenic (a) (as an antimicrobial agent) The aromatic compounds of arsenic include some effective antimicrobial agents, some of which have found use in chemotherapy; however, some of these ‘arsenicals’ have been discontinued owing to toxicity. The antimicrobial activity of arsenicals appears to involve their reaction with thiol (−SH) groups within cells – resulting e.g. in the inhibition of many enzymes; LIPOIC ACID is particularly sensitive because arsenic can bridge the two thiol groups in this coenzyme. Apparently, pentavalent arsenic in an arsenical must be converted, in vivo, to the trivalent state before the arsenical can act as an antimicrobial agent. The selective activity of arsenicals is believed to be due to differences in the permeability of different types of cell. Microorganisms can be protected from arsenicals by e.g. thiols, p-aminobenzoic acid or quinoid dyes. Atoxyl (NH2 .C6 H4 .As(OH)2 O; p-aminophenylarsonic acid) was the first arsenical to be used against trypanosomiasis. Salvarsan (3,3′ -diamino-4,4′ -dihydroxyarsenobenzene) was formerly used e.g. for the treatment of syphilis and trypanosomiasis; it is oxidized in vivo to produce the toxic agent: 3-amino-4hydroxyphenylarsenoxide. This drug has now been superseded. Glycobiarsol (bismuth N-glycolyl-p-arsanilate) has been used for treating amoebic dysentery. Tryparsamide (p-N-phenylglycineamidoarsonic acid) has been used for late-stage trypanosomiasis (African trypanosomiasis: sleeping sickness). Note that arsenicals are not active against Trypanosoma cruzi (Chagas’ disease). 52

Ascetospora brucellosis, gonorrhoea, Haverhill fever, Lyme disease, rickettsioses, syphilis, tuberculosis, yaws; it may also be caused by certain viruses – e.g., parvovirus [Lancet (1985) i 419–421, 422–425], Ross River virus, rubella virus. Septic arthritis is due to infection of the synovial fluid – commonly by staphylococci – e.g. secondarily to OSTEOMYELITIS in an adjacent bone, or as a complication of septicaemia; S. epidermidis may cause chronic septic arthritis of the hip following total hip replacement. (See also RHEUMATOID ARTHRITIS and REITER SYNDROME.) Arthroascus A genus of fungi (family SACCHAROMYCETACEAE) which form yeast cells (which bud, often bipolarly, on a wide base) and true mycelium (which tends to break up into arthrospores). Asci are formed directly after conjugation between two cells. Non-fermentative; NO3 − is not assimilated. Species: A. javanensis, isolated e.g. from soil, fruit, rotting wood. [Book ref. 100, pp. 114–116.] Arthrobacter A genus of obligately aerobic, catalase-positive, asporogenous bacteria (order ACTINOMYCETALES, wall type VI – see also PEPTIDOGLYCAN) which occur in the soil. In culture the organisms initially grow as irregular, ‘lumpy’, pleomorphic rods, with or without primary branching, but stationary-phase cultures consist predominantly of spherical or ovoid cells; on subculture rod-shaped forms develop. Optimum growth temperature: ca. 25° C. Arthrobacter spp have an oxidative-type metabolism; they are not cellulolytic. GC%: ca. 59–66. Type species: A. globiformis. Arthrobotrys A genus of fungi of the HYPHOMYCETES. Species can grow saprotrophically and can trap and digest nematodes (see NEMATOPHAGOUS FUNGI); A. oligospora can also attack and kill other fungi [FEMS Ecol. (1985) 31 283–291]. arthroconidium Syn. ARTHROSPORE. Arthrocystis See EIMERIORINA. Arthroderma A genus of fungi of the GYMNOASCALES (anamorphs: CHRYSOSPORIUM; Trichophyton). arthrospore (arthroconidium) (1) An arthric CONIDIUM. (2) Any CONIDIUM formed by thallic conidiogenesis. Arthuria See UREDINIOMYCETES. Arthus reaction A severe local inflammatory skin reaction which involves a TYPE III REACTION; the reaction becomes maximal 3–12 hours after the intradermal administration of antigen, and involves erythema, oedema, and local haemorrhage and necrosis. Arthus-type reaction Any disorder, other than the classical ARTHUS REACTION, which involves a TYPE III REACTION – see e.g. FARMERS’ LUNG and GLOMERULONEPHRITIS. artichoke curly dwarf virus See POTEXVIRUSES. artichoke mottled crinkle virus See TOMBUSVIRUSES. artifact Syn. ARTEFACT. Artogeia rapae GV See BACULOVIRIDAE. ARV See HIV. arylsulphatase An enzyme which can hydrolyse aromatic sulphate esters at the O–S bond; arylsulphatases occur e.g. in some Aspergillus and Mycobacterium spp. arylsulphatase test A test used in the identification of Mycobacterium spp. Essentially, the test strain is grown in a liquid medium containing tripotassium phenolphthalein disulphate (TPD); ARYLSULPHATASE-positive strains cleave TPD to PHENOLPHTHALEIN which is detected by a colour change on addition of alkali after 10 days (for slow-growing strains) or after 3 or 7 days (for rapidly-growing strains). ascarylose 3,6-Dideoxy-b-L-mannopyranose: a sugar found e.g. in the LIPOPOLYSACCHARIDE of certain strains of Yersinia pseudotuberculosis (and in the eggs of Ascaris worms). Ascetospora A phylum of PROTOZOA [JP (1980) 27 37–58] which form spores containing one or more sporoplasms but

Melarsoprol (a derivative of benzenearsenous acid – a trivalent arsenical) is effective against both West and East African strains of the causal agent of sleeping sickness (Trypanosoma brucei gambiense and T. brucei rhodesiense, respectively). The specific target of the drug is trypanothione (N 1 ,N 8 bis[glutathionyl]spermidine) [PNAS (1989) 86 2607–2611]. Melarsoprol reacts with trypanothione to form an adduct (Mel T) which inhibits trypanothione disulphide reductase – an enzyme essential for regulating the parasite’s thiol/disulphide balance. Melarsoprol crosses the blood–brain barrier less readily than eflornithine, but it is still regarded as the most effective trypanocidal drug available for treating sleeping sickness [AP (1994) 33 1–47]. Trypanosomes exposed sub-lethally to arsenicals develop resistance quite readily, possibly owing to decreased uptake. (b)(in energy metabolism) Some bacteria use arsenate (or selenate) as electron acceptor in anaerobic respiration, electron donors including e.g. acetate, lactate and ethanol (according to species); cell-envelope reductases have been found [FEMS Reviews (1999) 23 615–627]. Arsenite is used as electron donor in autotrophic CARBON DIOXIDE fixation and as a respiratory electron acceptor [FEMS Ecol. (2004) 48 15–27; JB (2004) 186 1614–1619]. ART Automated reagin test: a qualitative or quantitative STANDARD TEST FOR SYPHILIS similar in principle to the RPR TEST. arteannuin Syn. QINGHAOSU. artefact (artifact) Any feature which does not occur in a specimen under natural conditions, but which may be seen in that specimen during experimentation. Artefacts are due to the disturbance introduced by the process of experimentation or observation; they may occur e.g. as a result of FIXATION. artemether See QINGHAOSU. artemisinine Syn. QINGHAOSU. arteritis Inflammation of an artery or arteries. Arterivirus A genus of viruses (family TOGAVIRIDAE); the arterivirus group currently includes LACTATE DEHYDROGENASE VIRUS, SIMIAN HAEMORRHAGIC FEVER VIRUS, the ‘Lelystad’ virus (see BLUE-EARED PIG DISEASE) and equine arteritis virus. In equines, equine arteritis virus causes necrosis of small arteries with various clinical manifestations – for example, rhinitis, oedema, enteritis, bronchopneumonia. Infection of pregnant mares commonly results in abortion. Transmission occurs both horizontally and vertically; vectors are unknown. The virus can infect a range of vertebrate cells in vitro. The viruses in this group are similar in their morphology and genomic organization; moreover, all exhibit a predilection for macrophages, and all tend to cause a lengthy period of viraemia. artesunate See QINGHAOSU. Arthonia See ARTHONIALES. Arthoniales An order of fungi of the ASCOMYCOTINA; members include crustose LICHENS (photobiont green, often trentepohlioid) and lichenicolous and saprotrophic fungi. Ascocarps are APOTHECIOID and may be lirelliform, irregular, etc; they contain paraphysoids. Asci are bitunicate, usually clavate. Genera: e.g. Arthonia. Arthopyrenia A genus of crustose LICHENS of the order DOTHIDEALES; ascospores have one to several septa. A. halodytes (photobiont ‘Hyella’) is a marine species which grows endolithically in calcareous rocks and on the shells of limpets, barnacles etc in the intertidal zone; it occurs in Europe and N. America. arthralgia Joint pain. arthric conidium See CONIDIUM. arthritis Inflammation of one or more joints. It may occur as a symptom or complication of various infectious diseases – e.g. 53

Aschaffenburg–Mullen phosphatase test no extrusion apparatus (no polar capsules or polar filaments). (cf. MICROSPORA; MYXOZOA.) The organisms are parasitic in invertebrates. Classes: PARAMYXEA and STELLATOSPOREA. Aschaffenburg–Mullen phosphatase test Syn. PHOSPHATASE TEST (for milk). Aschersonia A genus of fungi (order SPHAEROPSIDALES) which include parasites of scale insects and whiteflies. Strains of Aschersonia have been used e.g. in Florida for the biological control of scale insects. asci See ASCUS. ascigerous Bearing, or giving rise to, asci (see ASCUS). ascites The condition in which fluid (ascitic fluid) accumulates in the peritoneal cavity during certain pathological conditions. (See also INFECTIOUS DROPSY (of carp).) Ascobolus See PEZIZALES. ascocarp (ascoma) A structure at the surface of which, or within which, asci (see ASCUS) develop; the main forms of ascocarp are the APOTHECIUM, ASCOSTROMA, CLEISTOTHECIUM and PERITHECIUM. (Ascocarps are not produced e.g. by Saccharomyces spp and related yeasts.) In ascohymenial species ascocarp development appears to follow the sexual stimulus, i.e., plasmogamy (fertilization) precedes ascocarp development; in ascolocular species the initiation of ascocarp development (i.e., formation of a stroma) occurs before plasmogamy. In general, ascohymenial species form unitunicate asci, and ascolocular species form bitunicate asci. Ascochyta A genus of fungi of the order SPHAEROPSIDALES; A. pisi is the causal agent of leaf spot disease of the pea plant. Conidiophores are borne in dark, thick-walled, non-setose, unilocular, ostiolate pycnidia that are immersed in the host tissue. Ascocoryne See HELOTIALES. ascogenous ASCUS-forming. ascogone Syn. ASCOGONIUM. ascogonium (ascogone) In ascomycetes: the female GAMETANGIUM; it may be unicellular or multicellular, simple or complex in form, and it may or may not bear a TRICHOGYNE (according to species). ascohymenial See ASCOCARP. Ascoideaceae See ENDOMYCETALES. ascolichen An ascomycetous LICHEN. Ascoli’s thermoprecipitin test A serological PRECIPITIN TEST used to detect antigens of Bacillus anthracis (causal agent of ANTHRAX) in various animal products (e.g. hides). The material is extracted with e.g. boiling saline, and the extract is layered over a known positive antiserum in a RING TEST. ascolocular See ASCOCARP. ascoma Syn. ASCOCARP. ascomycetes Fungi of the subdivision ASCOMYCOTINA. (In some taxonomic schemes these fungi form the class Ascomycetes.) Ascomycotina (the ‘ascomycetes’) A subdivision of fungi (division EUMYCOTA) characterized by the formation of sexually derived spores (ASCOSPORES) in asci (see ASCUS). The ascomycetes are typically terrestrial saprotrophs or parasites; they include e.g. most YEASTS, the edible morels and TRUFFLES, the cup fungi, the POWDERY MILDEWS, BLACK MILDEWS and SOOTY MOULDS, and organisms which are better known in their asexual (‘deuteromycete’) states: the common ‘blue moulds’ and ‘green moulds’. Marine ascomycetes include members of the SPATHULOSPORALES. In most species the thallus is a well-developed, septate, branching mycelium in which the CELL WALL contains CHITIN (see also SEPTUM); however, some ascomycetes are unicellular organisms, and some are DIMORPHIC FUNGI.

In the typical life cycle, the germination of an ascospore leads to the development of a septate mycelium consisting of uninucleate, haploid cells. Many (but not all) ascomycetes then exhibit a conidial (= asexual, imperfect or anamorphic) phase in which conidia (see CONIDIUM) are formed; although the anamorph is part of the HOLOMORPH, anamorphs are commonly (for convenience) classified in the DEUTEROMYCOTINA. At some stage the thallus enters DIKARYOPHASE – e.g. by GAMETANGIAL CONTACT, SOMATOGAMY or SPERMATIZATION. Subsequently, karyogamy and MEIOSIS occur in the developing ASCOCARP – which commonly gives rise to asci which each contain 8 (haploid) ascospores. In the typical life cycle diplophase is thus of limited duration; however, in some ascomycetes (e.g. many yeasts) diplophase is dominant – plasmogamy and karyogamy quickly following ascospore formation, so that the vegetative cells are commonly diploid. In some taxonomic schemes [see e.g. Book ref. 64] classes are not recognized; instead, the ascomycetes are divided into 37 orders: ARTHONIALES; ASCOSPHAERALES; CALICIALES; CLAVICIPITALES; Coryneliales; Cyttariales; DIAPORTHALES; Diatrypales; DOTHIDEALES; ELAPHOMYCETALES; ENDOMYCETALES; ERYSIPHALES; EUROTIALES; GRAPHIDALES; GYALECTALES; GYMNOASCALES; HELOTIALES; HYPOCREALES; LABOULBENIALES; LECANIDIALES; LECANORALES; MICROASCALES; OPEGRAPHALES; OPHIOSTOMATALES; OSTROPALES; PELTIGERALES; PERTUSARIALES; PEZIZALES; POLYSTIGMATALES; PYRENULALES; RHYTISMATALES; SORDARIALES; SPATHULOSPORALES; SPHAERIALES; TAPHRINALES; TELOSCHISTALES; VERRUCARIALES. Ascophyllum See PHAEOPHYTA. L-ascorbic acid (vitamin C; L-threo-2,3,4,5,6-pentahydroxy-2-hexenoic acid-4-lactone) A VITAMIN, essential to man but not normally to microorganisms, found e.g. in fresh fruit and vegetables; it can be synthesized e.g. by certain algae and strains of Aspergillus niger. It is a strong reducing agent (oxidized form = dehydroascorbic acid) used e.g. as a poising agent in media for anaerobes (see REDOX POTENTIAL). Commercial manufacture (the Reichstein process) involves the hydrogenation of glucose to D-sorbitol followed by the SORBOSE FERMENTATION; L-sorbose is converted chemically to ascorbic acid. Ascoseira See PHAEOPHYTA. Ascosphaera See ASCOSPHAERALES. Ascosphaerales An order of fungi (subdivision ASCOMYCOTINA) which are associated with bees and pollen. Genera: Ascosphaera (see CHALKBROOD), Arrhenosphaera and BETTSIA. ascospore A SPORE formed within an ASCUS. According to species, ascospores may be septate or aseptate, and may be any of a variety of shapes, sizes and colours. On germination, the ascospores of most species form germ tube(s), while those of yeasts characteristically give rise to budding cells. Ascospore discharge. In most ascomycetes the ascospores are forcibly ejected from the ascus; forcible ejection can occur either from a UNITUNICATE ASCUS or from a BITUNICATE ASCUS. The mechanism of ascospore ejection appears to be unknown; however, ejection probably depends on the development of pressure within the ascus by the absorption of water – e.g. as a result of the enzymic breakdown of a polysaccharide with consequent increase in osmotic pressure. Different mechanisms may be involved in different ascomycetes. In apothecial ascomycetes (‘discomycetes’) the ascospores are often released simultaneously by a large proportion of the asci; this results in a visible cloud of ascospores and is called puffing. In cleistothecial ascomycetes the mature asci appear to swell up and rupture the cleistothecial wall. In some species the 54

asepsis protruding (or totally freed) asci release their ascospores by violent disintegration. In perithecial ascomycetes various strategies have evolved to ensure that the ascospores do not remain trapped within the perithecium. Thus, e.g. in Sordaria fimicola each of the hymenial asci, in turn, elongates, discharges its ascospores, and collapses. In ascomycetes which form long-necked perithecia the asci may become detached from the hymenium and are subsequently blown through the ostiole as a result of pressure in the perithecial cavity; however, in species of Ceratocystis the asci are evanescent, and the mature ascospores are slowly extruded in a slimy mass through the perithecial neck. In the ascostromal ascomycete Myriangium, ascospore discharge is necessarily preceded by disintegration of the stroma – which occurs as a result of weathering. Once exposed to the environment the (bitunicate) asci forcibly eject their ascospores. In e.g. Tuber spp (and other hypogean ascomycetes) the ascospores are not forcibly discharged. In such species ascospore dispersal is mediated e.g. by burrowing animals. Ascospore discharge can be strongly influenced by environmental conditions (e.g. light, humidity), and a distinct periodicity of spore discharge (‘endogenous rhythm’) has been detected in a number of species. In ascomycetes which form deeply concave (cupulate) apothecia the asci are commonly positively phototropic; asci which line the near-vertical walls of the apothecium thus direct their spores outwards (into the environment) rather than towards the opposite wall of the apothecium. In some fungi, e.g. Daldinia concentrica, ascospore discharge occurs mainly or exclusively in the dark. ascostroma An ASCOCARP consisting of a STROMA (sense 1) containing one or more cavities (locules), each locule containing one or more asci (see ASCUS). In each locule the CENTRUM is bounded only by the stromatic tissue; this contrasts with the ascocarp structure of those ascomycetes (e.g. Xylaria spp) which form perithecia immersed in a stroma: in such species a distinct perithecial wall occurs within the locule. A uniloculate ascostroma (i.e., one containing a single locule) may contain a hymenial layer of asci, and may thus resemble a perithecium; such a structure is referred to as a perithecioid pseudothecium or pseudoperithecium. (In e.g. Rhytidhysteron the hymenium forms an apothecium-like structure which is called an apothecioid pseudothecium.) In some ascomycetes (e.g. Myriangium) the asci develop in uniascal locules which are scattered irregularly in the stroma. An ascostroma may develop on the surface of, or within, the substratum. Ascotricha See SPHAERIALES. ascus (pl. asci) A microscopic, sac-like structure within which are formed the sexually derived (or, exceptionally, parthenogenically derived) spores (ASCOSPORES) of fungi of the subdivision ASCOMYCOTINA. Asci are commonly cylindrical or clavate, but can be e.g. cup-shaped, globose or dumb-bell-shaped, according to species; a mature ascus typically contains eight ascospores, but in some species it contains e.g. two or four ascospores, or (in e.g. Kluyveromyces and Lipomyces) more than eight ascospores. Asci may be formed within or at the surface of an ASCOCARP, and may occur singly, in groups, or in a closely packed layer (hymenium) which, according to species, may be interspersed with sterile structures (see e.g. PARAPHYSIS). In some species the asci are evanescent (see also PROTOTUNICATE ASCUS). Ascus formation is usually preceded by plasmogamy – which, depending on species, occurs by GAMETANGIAL CONTACT, GAMETANGIAL COPULATION, SOMATOGAMY or SPERMATIZATION. Many ascomycetes exhibit HETEROTHALLISM. (See also MATING TYPE.)

Following plasmogamy, the events leading to ascus formation vary according to species. Ascus formation in ascogenous yeasts. After plasmogamy (which may occur e.g. by the fusion of somatic cells or ascospores), karyogamy commonly follows without delay. The zygote may undergo MEIOSIS immediately (as e.g. in Schizosaccharomyces octosporus) so that the ascus develops directly from the zygote; alternatively, meiosis may be delayed for one or more mitotic divisions (e.g. as in the diploid budding phase of Saccharomyces cerevisiae) – in which case the ascus develops following meiosis in one of the diploid descendents of the zygote. Following meiosis, the four (haploid) nuclei may develop directly into four ascospores (as in e.g. S. cerevisiae) or there may be subsequent mitotic division with the eventual formation of e.g. eight ascospores (as in e.g. S. octosporus). The process by which a nucleus gives rise to an ascospore is called free cell formation (see below). Ascus formation in other ascomycetes. (The following is necessarily a generalized account since details of the process vary from species to species.) After plasmogamy, karyogamy is typically delayed. One or more hyphae (ascogenous hyphae) arise from the ASCOGONIUM, and the (haploid) male and female nuclei migrate into these hyphae. The tip of each hypha then curves to form a crook (crozier) such that two nuclei (one from each parent) occur in the curved upper portion of the crozier. These nuclei then undergo mitosis, simultaneously, with their mitotic spindles arranged parallel to the long axis of the ascogenous hypha; the subsequent formation of a septum creates an apical cell (the ascus mother cell ) which contains one daughter nucleus from each of the two original nuclei. Karyogamy now occurs. The zygote undergoes meiosis followed by one or more mitotic divisions to produce the number of haploid nuclei (ascospore initials) characteristic of the species. The ascospores develop by free cell formation. In this process, each nucleus (with a portion of cytoplasm) becomes enclosed within an envelope (the spore-delimiting membrane, SDM) composed of two unit-type membranes. In some ascomycetes (e.g. many members of the Endomycetales) the nucleus may be enveloped directly by vesicles (derived from the GOLGI APPARATUS or Golgi-equivalent?) which develop in association with the SPINDLE POLE BODY. In other species, e.g., Taphrina deformans and some species of Tuber, each nucleus becomes enveloped by membrane derived from invaginations of the ascus plasma membrane. However, in most ‘euascomycetes’ the SDMs derive from a system of nuclear and/or endoplasmic reticular membranes which, initially, form a discontinuous layer around the periphery of the ascus cytoplasm (the peripheral membrane cylinder ). That portion of the ascus cytoplasm which is not incorporated into ascospores is termed the epiplasm. Ascospore wall material is subsequently laid down between the two layers of the SDM. [Ascospore development: Book ref. 175, pp. 107–129.] Types of ascus. There are at least nine morphologically and/or functionally distinct types of ascus [Bot. J. Lin. Soc. (1981) 82 15–34 (29–33)]: see e.g. ANNELATE ASCUS, BITUNICATE ASCUS, OPERCULATE ASCUS, OSTROPALEAN ASCUS and PROTOTUNICATE ASCUS. (See also UNITUNICATE ASCUS and BILABIATE.) ascus mother cell See ASCUS. Asellariales See TRICHOMYCETES. asepsis (1) The state in which potentially harmful microorganisms (e.g. pathogens in a medical context, spoilage organisms in an industrial context) are absent from particular tissues, materials or environments; in this sense asepsis does not necessarily 55

aseptate involve sterility (cf. STERILE (sense 1)). (2) A state of sterility. (See also ANTISEPSIS and STERILIZATION.) aseptate Lacking septa – see SEPTUM. aseptic (adj.) Refers to ASEPSIS (sense 1 or 2). aseptic meningitis See MENINGITIS (b). aseptic technique Precautionary measures taken to prevent the contamination of cultures, sterile media etc and/or the infection of persons, animals or plants by extraneous microorganisms. Thus, e.g. all vessels for media etc must initially be STERILE (presterilized disposable petri dishes, syringes etc are often used). The working surfaces of instruments (forceps, LOOPS etc), and the rims of bottles used for dispensing sterile (non-flammable) materials, are sterilized by FLAMING. Before use, sterile material should not be exposed to non-sterile material or conditions. The risk of contamination is reduced by treating bench surfaces etc with DISINFECTANTS and/or with ultraviolet radiation (see STERILIZATION). Procedures (e.g. INOCULATION) are carried out in such a way that exposure to the atmosphere is reduced to a minimum, or is eliminated (see e.g. SAFETY CABINET). Ashbya See METSCHNIKOWIACEAE and STIGMATOMYCOSIS; see also RIBOFLAVIN. AsiA See ANTI-SIGMA FACTOR. Asian flu See INFLUENZAVIRUS. Asiatic cholera Syn. CHOLERA. ASLT ANTISTREPTOLYSIN O TEST. ASO test ANTISTREPTOLYSIN O TEST. ASOT ANTISTREPTOLYSIN O TEST. L-asparaginase (L-asparagine aminohydrolase; EC 3.5.1.1) An enzyme which hydrolyses L-asparagine to L-aspartate and NH3 . L-Asparaginase (e.g. from Escherichia coli or Citrobacter sp) is used as an anticancer agent – e.g. for treating acute lymphocytic leukaemia in which the cancer cells require exogenous asparagine. (See also ENZYMES.) L-asparagine biosynthesis See Appendix IV(d). asparenomycins CARBAPENEM antibiotics. aspartame L-Aspartyl-L-phenylalanine methyl ester; it is used as a sweetener in certain foods and beverages. aspartase See ASPARTATE BIOSYNTHESIS. aspartate ammonia-lyase See ASPARTATE BIOSYNTHESIS. L-aspartate biosynthesis For the main pathway of aspartate biosynthesis see Appendix IV(d). In many microorganisms, aspartate can also be produced from fumarate and ammonia by the enzyme aspartase (L-aspartate ammonia-lyase, EC 4.3.1.1), but this (reversible) reaction is probably more important in the deamination of aspartate than in its synthesis. (cf. IMMOBILIZATION sense 1.) aspartokinase See Appendix IV(d). aspergillic acid An antibiotic (a pyrazine derivative) formed by Aspergillus flavus. aspergilloma See ASPERGILLOSIS. aspergillosis Any disease of man or animals in which the causal agent is a species of ASPERGILLUS. In man, the causal agent is usually A. fumigatus, although A. flavus, A. niger or A. terreus may be involved. Infection usually occurs by inhalation of air-borne conidia, but may occur via wounds or by ingestion. The disease may be noninvasive, the fungus colonizing a pre-existing lung cavity (e.g. a lung cyst or healed tuberculosis lesion) and forming compact mycelial masses called aspergillomas (cf. MYCETOMA sense 2); symptoms may be absent or may include chronic productive cough and haemoptysis. Less commonly, the disease may become invasive, disseminating to other organs (particularly in immunocompromised patients); this form is commonly fatal.

In some (atopic) individuals inhalation of Aspergillus conidia can lead to allergic bronchopulmonary aspergillosis (‘extrinsic bronchial asthma’); the conidia may germinate in the bronchi and sputum plugs, but the hyphae do not normally invade the tissues. Other forms of aspergillosis include e.g. infections of the ear or paranasal sinuses. Lab. diagnosis: cultural or microscopical (or histological) examination of e.g. biopsy material; repeated isolation of Aspergillus (e.g. from sputum) is presumptive evidence of infection. In some forms of aspergillosis specific antibodies may be demonstrated by gel diffusion techniques. Aspergillosis can affect a wide range of animals, causing e.g. pneumonia, gastroenteritis (e.g. in calves), or placentitis leading to abortion (e.g. in cattle, sheep and horses). Birds (including poultry) are particularly susceptible; almost any organ can be affected, and the disease may be acute and (usually) fatal (as in ‘brooder pneumonia’ of baby chicks) or chronic (in adult birds). (See also AFLATOXINS.) Aspergillus A genus of fungi of the class HYPHOMYCETES: some species are known to have ascomycetous teleomorphs (see later). The organisms are widespread in nature, and are characteristically saprotrophic; they can use a wide range of substrates as nutrients. Some species can be pathogenic (see e.g. ASPERGILLOSIS, MADUROMYCOSIS, STONEBROOD), and many produce toxins (see e.g. AFLATOXINS, ASTELTOXIN, CYCLOPIAZONIC ACID, FESCUE FOOT, GLIOTOXIN, OCHRATOXINS, PATULIN, STERIGMATOCYSTIN). Some species can cause deterioration in various types of material (see e.g. BREAD SPOILAGE, CHEESE SPOILAGE, COAL BIODEGRADATION, GLASS, LEATHER SPOILAGE, PAINT SPOILAGE, PAPER SPOILAGE, PETROLEUM), while certain species are used in the manufacture of particular enzymes, foods or other commodities (see e.g. AMYLASES, BRINASE, CATALASE, CITRIC ACID, COFFEE, GLUCOSE OXIDASE, HAMANATTO, KOJI, MISO, PECTIC ENZYMES, SAKE, TAKADIASTASE). Aspergillus spp form a well-developed, septate mycelium. (See also NIGERAN and PSEUDONIGERAN.) Each conidiophore, which develops from a FOOT CELL (sense 2), consists of an erect hypha which has a more or less spherical terminal swelling (the ampulla or vesicle). In some species the ampulla is partly or completely covered by a layer of phialides (‘primary sterigmata’) – see CONIDIUM; in most species, however, the ampulla is covered by a layer of short, finger-like extensions (‘primary sterigmata’ or metulae) which give rise to the phialides (‘secondary sterigmata’) at their distal ends. Each phialide produces a basipetally formed chain of spherical, pigmented, aseptate conidia which, according to species, may be e.g. yellow, green or black. (Spore colour can also vary according to available trace elements in the medium; thus, e.g. A. niger may form yellow (instead of the normal black) conidia if levels of copper are low.) The ampulla, together with its metulae and/or phialides and associated chains of conidia, is called a conidial head. A PARASEXUAL PROCESS occurs e.g. in A. nidulans. Species include e.g. A. flavus, A. fumigatus, A. glaucus (teleomorph: EUROTIUM), A. nidulans (teleomorph: EMERICELLA), A. niger, A. oryzae, A. parasiticus, A. phialiseptus, A. terreus and A. versicolor. A. fumigatus (teleomorph: SARTORYA) is a major cause of aspergillosis in man. In the conidial head, the ampulla may appear domed (rather than spherical) owing to the gradual widening of the distal end of the conidiophore, and it bears a layer of phialides over the distal half to three-quarters of its surface; the proximally situated phialides are longer, and are inclined such that their free ends tend to be parallel with the more distal phialides – the chains of grey-green, spherical conidia thus 56

Astrephomene forming a parallel-sided columnar spore mass which may reach ca. 1 mm in length. A. fumigatus has been reported to grow at 50° C. (See also FUMAGILLIN.) A. phialiseptus is morphologically similar to A. fumigatus, but it forms septate phialides which are longer than those of A. fumigatus. Aspidisca A genus of ciliate protozoa (order HYPOTRICHIDA) related to Euplotes but differing e.g. in typically having a relatively reduced oral ciliature; species occur in freshwater and marine habitats, and e.g. in some SEWAGE TREATMENT plants. aspirin See PROSTAGLANDINS. asporogenous Not capable of forming spores. assay host (plant virol.) Syn. LOCAL LESION host. assimilatory nitrate reduction The (typically aerobic) reduction of nitrate to ammonia, the ammonia being assimilated as a source of nitrogen (see AMMONIA ASSIMILATION); nitrate can be used as the sole source of nitrogen by many bacteria, various fungi, and most algae and plants. Nitrate is initially reduced to nitrite – typically by a soluble, oxygen-insensitive enzyme (assimilatory nitrate reductase) in a reaction in which the electron donor may be a reduced pyridine nucleotide or a reduced ferredoxin; in fungi the electron donor is often (sometimes specifically) NADPH, but in e.g. Candida nitratophila it can be either NADH or NADPH [JGM (1986) 132 1997–2003]. The assimilatory reduction of nitrate to nitrite does not generate proton motive force – cf. DISSIMILATORY NITRATE REDUCTION. Nitrite is reduced to ammonia by an assimilatory nitrite reductase, reducing power being derived (according to organism) from NADPH, NADH or reduced ferredoxin – commonly the latter in algae and higher plants. The synthesis/activity of enzymes involved in assimilatory nitrate reduction is regulated at least partly by the extracellular concentrations of ammonia and nitrate. assimilatory sulphate reduction Sulphate can be used as the sole source of sulphur by most microorganisms. The major assimilatory pathway in bacteria and fungi is shown in the figure. (cf. DISSIMILATORY SULPHATE REDUCTION; see also SULPHUR CYCLE.) Astasia See EUGLENOID FLAGELLATES. astaxanthin See PHAFFIA. asteltoxin A polyene MYCOTOXIN isolated from toxic maize meal cultures of Aspergillus stellatus (= A. variecolor, Emericella variecolor ). In experimental animals asteltoxin can cause e.g. paralysis of hind-limbs and respiratory impairment. aster (cell biol.) See MITOSIS. aster yellows See YELLOWS. Asterionella A genus of freshwater and marine planktonic pennate DIATOMS. A. formosa occurs e.g. in lakes and reservoirs, forming blooms in spring and, to a lesser extent, in autumn. In this and other species each individual vegetative cell is long and narrow with slightly flared ends; a variable number of cells (ca. 8 under optimum conditions) form a star-shaped colony in which each corner of one end of a given cell is joined to one corner of a neighbouring cell. Asticcacaulis A genus of chemoorganotrophic, strictly aerobic PROSTHECATE BACTERIA; habitat and life-cycle are similar to those of CAULOBACTER, but one or more prosthecae arise subpolarly and/or laterally and do not have an adhesive role – adhesive material occurring on the cell surface. Astomatida An order of protozoa (subclass HYMENOSTOMATIA) in which the cells are typically large or long, are uniformly ciliated, contain a number of contractile vacuoles, lack a cytoproct, and are invariably mouthless; some species have an elaborate holdfast organelle. Asexual reproduction may involve budding

SO4

2−

ATP sulphate adenylyltransferase

PPi

APS ATP APS kinase ADP

PAPS +

NADPH + H

FAD thiol

PAPS reductase

+

NADP PAP

2−

SO3 +

3NADPH + 3H

sulphite reductase +

3NADP

3H2O

S2−

ASSIMILATORY SULPHATE REDUCTION in bacteria and fungi. APS = adenosine-5′ -phosphosulphate (see APS); PAPS = 3′ -phosphoadenosine-5′ -phosphosulphate; PAP = 3′ -phosphoadenosine5′ -phosphate. The pathway for the assimilation of sulphide depends on organism. In e.g. Escherichia coli sulphide is incorporated into O-acetylserine to form cysteine [Appendix IV(c)]. In e.g. Yarrowia (Saccharomycopsis) lipolytica sulphide may be incorporated into O-acetylserine (to form cysteine) or into O-acetylhomoserine to form homocysteine; homocysteine may be converted to methionine [Appendix IV(d)] or (via cystathionine) to cysteine [see e.g. MGG (1979) 174 33–38].

and (in e.g. Intoshellina) the formation of chain-like colonies. The organisms are endoparasites of e.g. annelids, molluscs and amphibians in freshwater and marine habitats. Genera include e.g. Anoplophrya, Cepedietta, Jirovecella, and Radiophrya. astomatous Refers to any structure or cell which does not have a pore, opening, or mouth. astome A member of the ASTOMATIDA. Astracantha See RADIOLARIA. Astraeus See SCLERODERMATALES. Astrephomene A genus of VOLVOX-like green algae which form spherical coenobia of 16–128 cells. 57

Astrolophus atovaquone See MALARIA. Atoxoplasma A genus of protozoa (suborder EIMERIORINA) similar to LANKESTERELLA but parasitic in birds. [Book ref. 18, p.13.] atoxyl See ARSENIC. ATP Adenosine 5′ -triphosphate (see figure). (See also NUCLEOTIDE.) In both prokaryotic and eukaryotic cells ATP actively participates in a range of processes and reactions which involve the conversion or expenditure of energy (see also ATPASE); energy derived from chemotrophic or phototrophic metabolism holds the mass–action ratio of the reaction (ATP ↔ ADP + Pi) at values such that ATP hydrolysis is thermodynamically highly favourable, i.e., it can yield free energy which the cell can use for specific purposes. (See also ADENYLATE ENERGY CHARGE.)

Astrolophus See ACANTHAREA. astropyle See RADIOLARIA. astroviruses Spherical, ether-resistant viruses, 29–30 nm diam., which have a characteristic five- or six-pointed star-shaped surface pattern. Astroviruses have been observed in normal and diarrhoeic faeces and may cause gastroenteritis in infants, calves, lambs and piglets. Lamb astrovirus apparently contains ssRNA [JGV (1981) 53 47–55]. ASW Artificial seawater. [Recipes: Book ref. 2, p. 436.] asymmetric PCR A variant form of PCR in which one of the two types of primer in the reaction mixture is used at a much lower concentration (e.g. 1:50) – so that this primer will be used up quickly when cycling begins; a normal concentration of the other primer ensures that one strand of the amplicon will be significantly amplified. Asymmetric PCR can be used for preparing single-stranded DNA products suitable e.g. for DNA SEQUENCING. An alternative procedure for obtaining ssDNA products from PCR involves tagging one of the two types of primer with BIOTIN, both primers being used at normal concentrations [NAR (1996) 24 3645–3646]. After cycling, STREPTAVIDIN is added to the reaction mixture; streptavidin binds to the biotinylated products, i.e. it binds to one of the two types of ssDNA product (but not to the complementary product). Gel electrophoresis in a denaturing gel (which inhibits hybridization between the complementary ssDNA products) separates the two types of product because the electrophoretic mobility of the streptavidin-bound product is greatly reduced. If a particular product strand is required, the primer which forms the other strand is biotinylated. asymmetric unit membrane See UROPLAKIN. asymptomatic Without symptoms. AT type See BASE RATIO. ATCC American Type Culture Collection, 12301 Parklawn Drive, Rockville, Maryland 20852, USA. ateline herpesvirus See e.g. GAMMAHERPESVIRINAE (‘Herpesvirus ateles’). Athalamida See GRANULORETICULOSEA. atherosclerosis See MAREK’S DISEASE. Athiorhodaceae See RHODOSPIRILLACEAE. athlete’s foot (tinea pedis) RINGWORM of the foot, characterized by itching (often with cracking and scaling) of the skin – particularly that between the toes. Causal agents: usually Epidermophyton floccosum or Trichophyton spp; Candida albicans (see CANDIDIASIS) can cause a similar condition. athymic Lacking a thymus. Atkinsiella A genus of fungi (order SAPROLEGNIALES) which include organisms parasitic on e.g. the eggs of marine crustacea. Species include A. dubia, A. entomophaga and A. hamanaensis [Book ref. 1, pp. 201–202]. ATL ADULT T-CELL LEUKAEMIA. Atmungsferment Cytochrome aa3 . atomic mass unit (AMU; u) A unit of atomic mass: one-twelfth of the mass of a neutral 12 C atom; it is ca. 1.6605655 × 10−24 gram. (cf. DALTON; RELATIVE MOLECULAR MASS.) Atopobium A genus of asporogenous, obligately anaerobic, catalase-negative Gram-positive bacteria; cells: short rods or cocci which occur singly, in pairs or short chains. Non-motile. Glucose is metabolized to lactic, acetic and formic acids. A. parvulus was formerly classified as Streptococcus parvulus. GC%: 35–46. Type species: A. minutum. [Proposal for the genus Atopobium: FEMS (1992) 95 235–240.] atopy An inherited tendency to develop immunological HYPERSENSITIVITY states.

NH2 N O

O O−

g

P

O−

O

b

P

O−

O O P

a

O−

5′

O CH2 4′

H

N

O

H

N

H

3′

2′

OH

OH

N

1′

H

ATP (adenosine 5′ -triphosphate)

The phosphorylation of ADP to ATP commonly occurs by OXIDATIVE PHOSPHORYLATION, photophosphorylation or SUBSTRATE-LEVEL PHOSPHORYLATION; in some organisms PYROPHOSPHATE hydrolysis by a PROTON PPASE can be coupled to ADP phosphorylation via proton motive force (see CHEMIOSMOSIS).

In some energy-requiring reactions nucleotides other than ATP may be used; thus, e.g., guanosine 5′ -triphosphate (GTP) is involved in certain stages in PROTEIN SYNTHESIS. Small amounts of ATP can be detected e.g. by techniques which involve CHEMILUMINESCENCE. ATP-binding cassette See ABC TRANSPORTER. ATP synthase See ATPASE. ATPase Adenosine 5′ -triphosphatase: any of a wide range of structurally and functionally distinct enzymes and enzyme complexes capable of hydrolysing a phosphate bond in ATP (q.v.) – cf. KINASE; many types of ATPase (sometimes called ATP synthases) can catalyse the synthesis of ATP (see e.g. OXIDATIVE PHOSPHORYLATION) as well as the hydrolysis of ATP. Most ATPases appear to be g-phosphohydrolases, i.e., they catalyse the dephosphorylation of ATP to adenosine 5′ -diphosphate (ADP) and inorganic phosphate (Pi), and/or the converse reaction. Energy derived from the hydrolysis of ATP by a given ATPase may be used, directly, in one or other of two main types of energy-requiring activity: (a) energy conversion and/or the transmembrane translocation of ions (see e.g. PROTON ATPASE and ION TRANSPORT); (b) mechanical work (see e.g. PRIMOSOME and eukaryotic FLAGELLUM). By generating or augmenting proton motive force (see CHEMIOSMOSIS), ATP hydrolysis can supply energy for some functions (e.g. rotation of the bacterial FLAGELLUM) that cannot use ATP as a direct source of energy. Note on nomenclature. The activity of some proton-translocating ATPases is enhanced by specific ions – e.g. the cytoplasmic membrane of Escherichia coli contains a ‘Ca2+ , 58

aurintricarboxylic acid ALPHAHERPESVIRINAE).

Infection probably occurs mainly via the upper respiratory tract; the virus then invades the nervous system. In piglets, symptoms may include vomiting or diarrhoea, fever, trembling, incoordination, convulsions, and prostration; mortality rates may reach 100% in neonates. In adult pigs infection may be asymptomatic or may result in e.g. fever, respiratory symptoms, anorexia, and abortion; recovery usually occurs in a few days. A carrier state is recognized. In cattle, dogs and cats, the disease may resemble the active form of RABIES, with signs of intense itching, salivation, convulsions, and death. [Book ref. 27.] Aulacantha See RADIOLARIA. Aulosira A phycological genus of filamentous ‘blue-green algae’ (Nostocales) in which both heterocysts and akinetes are formed (cf. CYANOBACTERIA section IV). AUM See UROPLAKIN. Aura virus See ALPHAVIRUS. auramine O A basic, yellow, substituted diphenylmethane FLUOROCHROME; fluorescence: yellow. auramine–rhodamine stain A fluorescent ACID-FAST STAIN. The stain is made by mixing auramine O (1.5 g) and rhodamine B (0.75 g) with distilled water (25 ml) and melted phenol (10 ml); this mixture is added to distilled water (25 ml) and glycerol (75 ml), well mixed, and filtered through glass wool. A heat-fixed smear is stained for 15–20 min at 37° C and rinsed in distilled water. Decolorization, for 2–3 min, is attempted with 70% ethanol containing 0.5% v/v conc. HCl. The smear is washed in distilled water and then flooded with ‘counterstain’ (0.5% aqueous potassium permanganate) for ca. 2 min to suppress non-specific fluorescence of tissue debris etc. (Prolonged counterstaining would mask the fluorescence of acid-fast organisms in the smear.) The smear is then washed in distilled water, blotted dry, and examined by fluorescence MICROSCOPY. Aureobasidium (Pullularia) See HYPHOMYCETES; see also BLACK YEASTS; PAINT SPOILAGE; PULLULAN; SAP-STAIN. aureofungin An antifungal antibiotic of the heptaene group of POLYENE ANTIBIOTICS produced by Streptoverticillium cinnamomeum var. terricolum; it is a golden-yellow powder which is insoluble in water but soluble in dilute alkali or ethanol. Aureofungin is active against a wide range of plant-pathogenic fungi, is translocated within the plant, and has been used e.g. for crop spraying and for the prevention of seed-borne disease. [Book ref. 121, pp. 137–148.] aureomycin See TETRACYCLINES. Auricularia A genus of fungi of the order AURICULARIALES. A. auricula-judae (the ‘Jew’s ear fungus’) can be parasitic e.g. on elder (Sambucus). An edible species, A. polytricha, is cultivated on oak (Quercus) in China. (See also FUNGUS GARDENS.) Auriculariales An order of fungi (subclass PHRAGMOBASIDIOMYCETIDAE) which typically form elongated, transversely septate basidia in gymnocarpous or semiangiocarpous fruiting bodies which may be e.g. stalked or sessile, and which are characteristically gelatinous or waxy; the basidiocarp may be e.g. cup-shaped or ear-shaped. Some species are saprotrophs; others are parasitic e.g. on mosses and on other fungi. Genera include e.g. AURICULARIA, Helicobasidium and Phleogena. aurintricarboxylic acid (ATA) A TRIPHENYLMETHANE DYE which inhibits PROTEIN SYNTHESIS in prokaryote and eukaryote cell-free extracts; it appears to inhibit the binding of mRNA to ribosomes and, at higher concentrations, can inhibit chain elongation. ATA strongly chelates metal ions.

Mg2+ -stimulated ATPase’; confusingly, this terminology is also used for some ATPases which translocate ions other than protons: see e.g. ION TRANSPORT. ATP-gS Adenosine-5′ -(g-thio)triphosphate: a (biologically) nonhydrolysable ATP analogue. atractyloside A glucoside, produced by the Mediterranean thistle (Atractylis gummitera), which competitively inhibits the ADP/ATP exchange carrier system in the mitochondrial inner membrane. (cf. BONGKREKIC ACID; WEDELOSIDE.) AtrB An ABC TRANSPORTER in Aspergillus nidulans. atrichous (1) Hairless. (2) Lacking flagella. (3) Lacking any filamentous appendages (flagella, fimbriae etc). atrium (ciliate protozool.) A shallow concavity in the cytostomal region – particularly in certain hypostomes. att site A DNA sequence at which site-specific recombination occurs during integration of the genome of a temperate bacteriophage into the chromosome of its host; the site on the phage genome is designated attP, that on the host chromosome attB. (See e.g. BACTERIOPHAGE l.) attaching and effacing lesions See EPEC. attB site See ATT SITE. attenuated (1) Of e.g. a structure: becoming narrow; tapered. (2) Having a reduced virulence – see ATTENUATION (1) and (2). attenuated vaccine A VACCINE containing live pathogens whose virulence for a given host species has been reduced or abolished by ATTENUATION. attenuation (1) (immunol.) Any procedure in which the virulence of a given (live) pathogen for a particular host species is reduced or abolished without altering its immunogenicity; attenuation may be achieved by SERIAL PASSAGE and may be used to prepare VACCINES (e.g., the SABIN VACCINE). (2) A reduction in the virulence of a pathogen under natural conditions. (3) See SPIRITS. (4) (mol. biol.) See OPERON. attenuator See OPERON. attP site See ATT SITE. atypical interstitial pneumonia (of cattle) Any of a clinically distinct group of acute or chronic respiratory diseases which typically involve e.g. pulmonary emphysema and oedema, hyperplasia of alveolar epithelium and interstitial cells, and an unresponsiveness to treatment [Book ref. 33, pp. 1255–1261]. (cf. BOVINE RESPIRATORY DISEASE.) In no naturally occurring case has the causal agent been established with certainty; causes may include the effects of noxious gases, metabolic products (see FOG FEVER), dusts (see BOVINE FARMERS’ LUNG), a ketone constituent of the weed Perilla frutescens, or IPOMEANOL. (See also PNEUMONIA.) atypical mycobacteria (anonymous mycobacteria) Species of MYCOBACTERIUM which can cause disease in man but which (unlike M. tuberculosis and M. bovis) do not cause fatal, disseminated disease when inoculated into guinea pigs. Atypical mycobacteria often give a negative NIACIN TEST. Au antigen See HEPATITIS B VIRUS. Audouinella See RHODOPHYTA. Aufwuchs (periphyton community) Organisms (including certain algae and sessilinids) which colonize and form a coating on submerged objects (stones, plants, etc) in aquatic habitats. Augmentin A mixture of AMOXYCILLIN and CLAVULANIC ACID used e.g. in the treatment of urinary tract infections. Augusta disease (of tulips) See TOBACCO NECROSIS VIRUS. Aujeszky’s disease (pseudorabies; mad itch; infectious bulbar paralysis) A PIG DISEASE which may also affect e.g. cattle, dogs, cats and rats; it occurs in North America, Europe, S. E. Asia, and the UK. The causal agent is a herpesvirus (see 59

aurodox aurodox See POLYENE ANTIBIOTICS (b). aurovertins A group of polyene, a-pyrone-containing MYCOTOXINS isolated from cultures of Calcarisporium arbuscula. [Biosynthesis: PAC (1986) 58 239–256.] Aurovertins bind noncovalently to, and inhibit, (F0 F1 )-type PROTON ATPASES. Australia antigen HBsAg: see HEPATITIS B VIRUS. Australia X disease Syn. MURRAY VALLEY FEVER. Australian bat lyssavirus See LYSSAVIRUS. auto-agglutination (saline agglutination) Spontaneous agglutination which may occur when bacterial cells (or other particulate materials) are suspended in e.g. saline. (See also VW ANTIGENS.) auto-a Syn. ALPHA PEPTIDE. autoantibody An ANTIBODY produced by an individual against one of its own antigens. (See e.g. TYPE V REACTION.) autoantigen An antigen homologous to an AUTOANTIBODY. Autobiocounter M 4000 See HACCP. autocatalytic splicing See SPLIT GENE (b, c and e). autochthonous (1) Indigenous to a given environment. (cf. ALLOCHTHONOUS.) In a given environment the autochthonous microorganisms maintain more or less constant numbers or

biomass – reflecting more or less constant (albeit typically low) levels of nutrients. (cf. ZYMOGENOUS.) (2) (immunol.) Syn. AUTOLOGOUS. autoclave An apparatus within which objects or materials can be heat-sterilized by (air-free) saturated steam, under pressure, at temperatures usually in the range 115–134° C. (The pressure itself plays little or no part in the STERILIZATION process – which depends on the combined effects of heat and water vapour.) The simplest (‘bench-type’) autoclaves resemble the domestic pressure cooker in both principle and appearance. Material to be autoclaved is placed on a rack in the chamber and the lid clamped securely in position with the valve open; water in the bottom of the chamber is boiled (by means of an internal electric element, or by external heating) and the steam allowed to escape, via a valve in the lid, until all the air has been displaced from the chamber. The valve is then closed; on further heating, water continues to vaporize, and the pressure and temperature of the steam rise to levels determined by the setting of the steam exhaust valve – which then opens to maintain the required pressure and temperature of steam in the chamber. For a given

B

D

C

A E

chamber F D

F

steam inlet 275-550 kPa (40-80 lb/inch2)

C

H G

J K

steam/condensate outlet

AUTOCLAVE. Simplified, diagrammatic representation of a Series 225 steam–mains autoclave (courtesy of Baird and Tatlock (London) Ltd). A. Steam inlet valve. The valve is opened/closed electromagnetically – its operation being governed by the pressure controller/indicator. (Control by temperature – via the thermocouple – is an available option.) B. Pressure controller/indicator. C. Door microswitch – a safety device; electrical power is connected to the autoclave only when the microswitch has been actuated, i.e., when the door has been fully closed. Additionally, this device automatically opens the steam exit valve if any attempt is made to open the door while the chamber is under pressure. D. Door closure bolts which operate microswitches. E. Safety valve set to open at 275 kPa. F. Filters which prevent blockage of steam discharge lines and steam trap. G. Thermocouple pocket: temperature control/indicator/recording option. H. Manually-operated by-pass valve – can be operated in case of electrical power failure. (Under such conditions valve J could not be opened.) The valve contains a built-in bleed which permits a small but continual flow of steam from the chamber to the exterior. J. Electrically-operated steam exit valve. K. Steam trap. Operational sequence. 1. Insert load. 2. Secure door. 3. Set controls for required pressure/temperature and sterilizing time. 4. Switch on power. Steam enters the chamber through A, and the downwardly-displaced air is purged, via filters F, through (a) the steam trap K and (b) the permanent bleed H; J is closed, and when steam leaves the chamber, K closes. A closes when the chamber pressure reaches the selected value. Steam continues to leave the chamber via the permanent bleed H – permitting continual temperature monitoring by the thermocouple G; since G is located at the lowest (and hence coolest) part of the system, it measures the ‘worst case’ temperature – the chamber temperature always being higher than that registered by G. Sterilizing conditions within the chamber are maintained (against heat losses and against the continual steam bleed) by periodically admitting a pulse of steam via A. At the end of the sterilization cycle steam is discharged from the chamber via J; when atmospheric pressure has been re-established in the chamber the door can be opened and the load withdrawn. Automatic timing of the sterilization cycle commences when the chamber pressure (or, optionally, temperature – measured by G) reaches the desired value.

60

autogamy the entry of contaminated air is prevented by the presence of a filter in the air intake line. In vacuum autoclaves steam can be removed, and materials dried, by connecting a vacuum line to the chamber. Regular monitoring of an autoclave’s performance is important; monitoring devices should be used to check the temperatures reached at a number of different locations within the chamber. Monitoring devices may be physical (e.g. thermocouples), chemical (e.g. BROWNE’S TUBES), or biological (test envelopes containing the endospores of e.g. Bacillus stearothermophilus). In biological monitoring the autoclaved spores are tested for viability by attempting to culture them; although such a process is directly related to the aim of autoclaving, it involves a builtin delay (i.e. the incubation time). (See also AUTOCLAVE TAPE; BOWIE–DICK TEST.) Some materials (e.g. petroleum jelly, liquid paraffin) cannot be sterilized by autoclaving owing to their impermeability to steam; such materials (and e.g. clean glassware) are usually sterilized in a HOT-AIR OVEN. (See also CHEMICLAVE; LOW-TEMPERATURE STEAM DISINFECTION; STEAMER; STERILIZER.) autoclave tape Paper tape (usually self-adhesive) which changes colour (or exhibits other visible changes) when exposed to sterilizing conditions in an AUTOCLAVE. (See also BOWIE–DICK TEST.) autocolony A colony (or coenobium) which develops within one cell of a parent colony and which, when released, resembles the parent colony (see e.g. SCENEDESMUS). (cf. AUTOSPORE.) autocompartmentalization See PROTEASOME. autocoupling hapten See HAPTEN. autodigestion (of lamellae) See BASIDIOSPORES. autodisplay (biotechnol.) Autotransporter-mediated display of recombinant proteins at the cell surface of Escherichia coli. In this method, the a domain of the AIDA-I autotransporter (see type IV systems in PROTEIN SECRETION) is replaced by a recombinant protein; this is done by preparing a fusion protein consisting of the sequence encoding the b domain and that encoding the (heterologous) recombinant protein. In one study, the a domain was replaced e.g. by the cholera toxin B subunit; cells with the (normal) outer membrane protease OmpT cleaved the (recombinant) a domain, which was released from the cell, but in mutant (ompT − ) cells, which lack a functional OmpT protease, the subunit was not cleaved, but displayed at the cell surface. [Autodisplay: JB (1997) 179 794–804.] autoecious Syn. HOMOXENOUS. autofluorescence See FLUORESCENCE. autogamy (self fertilization) In certain protozoa: a sequence of events which culminates in the fusion of haploid nuclei or gametes derived from a single cell; autogamy occurs e.g. in certain ciliates (e.g. Paramecium – but apparently not in e.g. Tetrahymena) and in some sarcodines. In Paramecium aurelia each of the two micronuclei undergoes meiosis; of the eight haploid pronuclei produced all except one disintegrate. The surviving pronucleus divides mitotically to form a pair of gametic nuclei; these nuclei subsequently fuse to form the (homozygous) zygotic nucleus (= synkaryon). Two mitotic divisions then occur; two of the resulting (diploid) nuclei become new micronuclei, the other two become macronuclei – the original macronucleus having disintegrated during the preceding events. During the next binary fission one macronucleus passes to each daughter cell; both micronuclei divide, mitotically, and a pair of micronuclei passes to each daughter cell – thus re-establishing the normal nuclear constitution.

steam temperature the time required for sterilization depends on the nature of the load – the rate of steam penetration and the heat capacity of the load being important considerations. Sterilizing temperature/time combinations used with bench-type or larger autoclaves are commonly 115° C (10lb/inch2 ; ca. 69 kPa) for 30–35 min; 121° C (15lb/inch2 ; ca. 103 kPa) for 15–20 min; 134° C (30 lb/inch2 ; ca. 207 kPa) for 4 min. These times may be varied according to e.g. the nature of the load and the nature and degree of contamination. Large autoclaves, used e.g. in hospitals and industry, often use steam piped direct from a boiler, and frequently incorporate automatic controls for timing etc (see Figure). (See also STEAM TRAP.) Steam quality is important for effective sterilization. If air is present in an operating autoclave, the temperature corresponding to a given pressure is lower than it would be in the complete absence of air; thus, air must be completely purged from the autoclave chamber, and all free space within the chamber must be filled with saturated steam at the required temperature and pressure. Saturated steam is steam which holds the maximum amount of water vapour for its temperature and pressure. (Saturated steam effects optimum heat transfer since it delivers up a large amount of latent heat when condensing on objects in the chamber during the initial (pre-sterilization) heating-up period.) In a bench-type autoclave the steam is necessarily saturated since it remains in contact with water in the chamber. In a larger autoclave, steam entering the chamber from a boiler should, for maximum efficiency, be dry as well as saturated, i.e., it should contain no water in the liquid phase. (Wet saturated steam contains droplets of water.) Superheated steam is an unsaturated vapour formed when the pressure of dry saturated steam (at constant temperature) is lowered, or when the temperature of dry saturated steam (at constant pressure) is raised in the absence of free water. Superheated steam tends to behave as a gas, and must be at temperatures higher than those of saturated steam to achieve sterilization; it may be formed e.g. when steam is piped from a boiler to a large autoclave – particularly at a pressure-reduction valve. In most large autoclaves steam enters near the top of the chamber, and air is purged by downward displacement; this may permit pockets of air to become trapped at the bottom of deep, empty vessels – e.g. bottles with small openings or long, narrow necks – and such regions may not be adequately exposed to sterilizing conditions. (Air may also be trapped in items of apparatus which are totally enclosed in a wrapping of e.g. aluminium foil.) In a vacuum autoclave air is purged from the chamber by connecting it briefly to a vacuum line; when steam subsequently enters the chamber it can penetrate more easily into flasks and between the fibres of surgical dressings etc so that the overall sterilizing time is reduced. At the end of the sterilization cycle in a large autoclave the steam inlet valve is closed (or closes automatically); the autoclave may be left to cool slowly, or steam within the chamber may be allowed to escape via the steam exit valve until pressure in the chamber is equal to that of the atmosphere – when the chamber can be safely opened. When bottles of liquid have been autoclaved the temperature and pressure in the chamber should be allowed to decrease slowly to prevent boiling and the consequent loss of contents and/or damage to bottles. (Screwcaps on bottles should always be loosened prior to autoclaving.) Sometimes a partial vacuum is allowed to form in the chamber as the steam condenses; this can be advantageous since it tends to dry materials (e.g. dressings) in the chamber. When ‘breaking the vacuum’, i.e. allowing ingress of air to the chamber, 61

autogenous regulation Since only the original complement of genes is involved, the potential for genetic change in autogamy is less than that in CONJUGATION; nevertheless, new combinations of alleles may be formed during the meiotic divisions. (See also ACTINOPHRYS and ACTINOSPHAERIUM.) In some organisms autogamy occurs spontaneously; in others it may be induced by starvation, ageing, radiation etc. autogenous regulation (mol. biol.) The regulation of expression of a gene or operon by its own product(s). (See e.g. RIBOSOME (biogenesis).) autogenous vaccine A VACCINE prepared by the culture and inactivation of pathogen(s) isolated from a patient and subsequently used to inoculate that patient. Autographa californica NPV See NUCLEAR POLYHEDROSIS VIRUSES. autoimmune disease Any disease directly attributable to AUTOIMMUNITY. In some autoimmune diseases (e.g. acquired haemolytic anaemias) antibodies play a significant role, but many autoimmune diseases are cell-mediated. (See also e.g. MULTIPLE SCLEROSIS.) autoimmunity An expression of IMMUNITY (1) in which the body directs immunological mechanism(s) against one or more of its own components. (See also TYPE V REACTION.) autoinducer See AUTOINDUCIBLE ENZYME and QUORUM SENSING. autoinducible enzyme A (repressible) enzyme whose induction in a given organism is brought about by the presence of a specific compound (autoinducer) that is produced by the organism itself (cf. enzyme induction in e.g. the LAC OPERON). An example is bacterial luciferase (see BIOLUMINESCENCE). In this system autoinducer is secreted by the bacteria and can accumulate to the critical, effective concentration (sufficient to bring about derepression) only when the organisms are in a confined environment (e.g. in the luminous organs of certain marine fish). autoinfection Infection resulting from the transfer of a pathogen from one site to another in the same individual (cf. RE-INFECTION). autologous (immunol.) Present in or derived from an individual’s own tissues. autologous blood transfusion See TRANSFUSION-TRANSMITTED INFECTION. autolysate The products of AUTOLYSIS. (See e.g. YEAST EXTRACT.) autolysin (autolytic enzyme) Any of a range of endogenous enzymes which, by degradation of certain structural cell components (e.g. PEPTIDOGLYCAN in bacteria), can bring about AUTOLYSIS or AUTOPHAGY; autolysins are apparently involved in normal processes of growth and development (e.g., spore germination; cell wall polymer extension and cell separation during normal growth). Mutant bacteria defective in autolysin activity may show e.g. abnormal growth forms (e.g. filaments) or resistance to antibiotics active against the wild-type. In prokaryotes, autolysins occur in the cell wall or (in Gram-negative species) in the periplasmic space, often as inactive precursors which are activated e.g. by proteases (see also BILE SOLUBILITY); in eukaryotes autolysins are sequestered in LYSOSOMES. autolysis The lysis of a cell due to the action of its AUTOLYSINS – usually following the death of the cell or tissue. autolytic enzyme Syn. AUTOLYSIN. automatic volumetric spore trap Syn. HIRST SPORE TRAP. autonomously replicating sequence See ARS. autophagy The digestion, by a eukaryotic cell, of some of its own internal components – e.g., during periods of starvation. (See FOOD VACUOLE.) autoplaque A plaque (in a bacterial lawn plate) which resembles that caused by a lytic bacteriophage, but in which no phage can

be demonstrated. Autoplaques occur e.g. in cultures of certain strains of Rhizobium leguminosarum biotype trifolii and seem to result from autolysis. autoplast A PROTOPLAST or SPHAEROPLAST which results from the action of an organism’s own autolytic enzymes. autoradiography (radioautography) The use of a photographic process to locate and/or quantify a radioactively-labelled substance previously incorporated in living cells or tissues; autoradiography can be used e.g. to study sites of biosynthesis, turnover rates, and transport. Initially, a radioactive substrate is taken up by the living cells, and the label becomes incorporated in structures, metabolites etc as would be the non-labelled analogue. (The labelled substrate may be introduced using a PULSE–CHASE TECHNIQUE; since radioactive labels can be injurious to cells, dose and duration of the pulse may have to be limited.) The cells/tissues are then prepared for microscopy (e.g., fixed, dehydrated, embedded, sectioned, stained). For ELECTRON MICROSCOPY the section (e.g. on a formvar-coated grid) is stained with e.g. lead citrate or uranyl acetate, and is coated with a thin (ca. 5 nm) layer of carbon; the carbon layer is then overlaid with a thin layer of photographic emulsion, and the whole preparation is left in the dark at e.g. 4° C for a period of the order of days or weeks. Each point source of radioactivity in the section will affect the overlying area of emulsion, giving rise (on developing and fixing the emulsion) to a local deposit of silver which, under the EM, commonly appears as a tangled filament. Under the light microscope each silver deposit appears as a dot or fleck. Since the silver deposits are superimposed on the tissue section, the cellular location of the radioactive components can be determined. For optimum resolution, the section, carbon layer, and emulsion layer must each be very thin; given a choice of suitable radioactive sources, it is preferable to use the one with the least emission energy. Low-energy radiators, e.g. 3 H, tend to affect a small area of the emulsion immediately above each point source; with radiators of high emission energy, e.g. 32 P, each point source gives a wide-angled cone of effective radiation which affects a larger area of emulsion. Radioactive precursors used for studying particular cell components include e.g. [3 H]thymidine (DNA), [3 H]glucose (polysaccharides), and [3 H]proline (proteins). [Book ref. 4, pp. 235–277.] autosome Any chromosome other than a sex chromosome. autospore (algol.) A type of spore, formed asexually, which is an exact morphological replica of the parent cell. The term is usually reserved for aplanospores produced by Chlorella and related algae, but is sometimes extended to include e.g. the planospores of e.g. BRACHIOMONAS. autotransporter See PROTEIN SECRETION (type IV systems). autotroph An organism which uses CARBON DIOXIDE for most or all of its carbon requirements (cf. HETEROTROPH; LITHOTROPH); all obligate autotrophs appear to be either chemolithotrophs or photolithotrophs, and ‘autotroph’ is often used with the implication of lithoautotrophy (see also CHEMOTROPH). In many autotrophs CO2 fixation occurs via the CALVIN CYCLE or via the REDUCTIVE TRICARBOXYLIC ACID CYCLE. Some ACETOGENS fix CO2 via a different pathway (sometimes called the ‘activated acetic acid pathway’) in which acetyl-CoA can be synthesized by the reduction of two molecules of CO2 (see ACETOGENESIS); a similar pathway occurs in Desulfovibrio baarsii in which the methyl and carboxyl groups of acetyl-CoA are derived from formate and CO2 respectively [FEMS (1985) 28 311–315]. An analogous pathway occurs in METHANOGENS. autoxidation Spontaneous oxidation by atmospheric oxygen: see e.g. OXIDATIVE RANCIDITY and SULPHUR CYCLE. 62

avermectins auxanogram See AUXANOGRAPHIC TECHNIQUE. auxanographic technique A procedure used e.g. for identifying the substances which a given organism can use as carbon sources, or for identifying the growth factor(s) required by an AUXOTROPH. To identify usable carbon sources, a plate of medium which lacks a carbon source is heavily inoculated with the test organism; a small quantity of one of each of a number of different carbon sources is then placed at a separate location on the plate. Following incubation, usable carbon sources are indicated by growth at their locations on the plate. The pattern of usable carbon sources (or e.g. nitrogen sources) is termed an auxanogram; closely related organisms which are characterized by different auxanograms are said to be different auxotypes (= auxanographic types). An analogous procedure is used for examining a suspected auxotroph; a solid MINIMAL MEDIUM is inoculated with the test organism, and to the plate are then added small, discrete amounts of (a) a mixture of amino acids, (b) a mixture of vitamins, and (c) one or more possible requirements for nucleic acid synthesis. Following incubation, growth at one or other location on the plate indicates the identity of the growth factor(s) required. If, for example, growth occurs at the location of the mixed amino acids, the analysis is continued by repeating the procedure with separate, discrete inoculations of individual amino acids until the specific requirement(s) is/are known. auxanographic type See AUXANOGRAPHIC TECHNIQUE. auxins PHYTOHORMONES which promote stem elongation and, in conjunction with CYTOKININS and/or GIBBERELLINS, play important roles in many plant processes; auxins, which are derivatives of tryptophan, are produced mainly at stem apices and in young leaves. Similar or identical compounds are also formed by certain microorganisms (including a number of plant pathogens). In many plants the main auxin appears to be indole 3-acetic acid (IAA, also known as ‘auxin’ or ‘heteroauxin’), a compound synthesized via the precursor indole 3-acetonitrile (IAN). In vivo, IAA can e.g. stimulate ETHYLENE production, but the mechanisms by which IAA functions in the overall regulation of growth are not well understood. Regulation of the in vivo level of IAA appears to involve an enzyme, ‘IAA-oxidase’, which oxidizes IAA to products which include 3-methylene-oxindole and indolealdehyde; this enzymic oxidation is stimulated e.g. by certain monophenols (e.g. p-coumaric acid) and by Mn2+ , and is inhibited by certain diphenol derivatives (e.g. CAFFEIC ACID, CHLOROGENIC ACID, QUERCETIN and SCOPOLETIN). Certain plant diseases of microbial causation are characterized by the presence of atypical levels of auxins in the diseased plants. Hyperauxiny (abnormally high levels of auxins) occurs in many diseases and can arise in various ways – see e.g. CLUBROOT, CROWN GALL, OLIVE KNOT and SCOPOLETIN. The nature of the relationship between hyperauxiny and disease development is not well understood. auxochrome In a DYE molecule: any ionizable group by means of which the CHROMOPHORE can bind to target molecule(s). auxospore See DIATOMS. auxotroph A strain of microorganism which lacks the ability to synthesize one or more essential growth factors; an auxotroph arises by the occurrence of one or more mutations in a PROTOTROPH. A medium used to culture a given auxotroph must contain any factors which the organism cannot synthesize: see COMPLETE MEDIUM and MINIMAL MEDIUM. Auxotrophy results from a cell’s genetically determined inability to produce (normal amounts of) functional enzyme(s)

which catalyse particular stage(s) in the synthesis of essential growth factor(s); such a block may involve (a) the complete absence of enzyme; (b) the presence of normal enzyme in subnormal amounts; (c) the presence of abnormal enzyme which is devoid of or has lowered enzymic activity. (See also SYNTROPHISM.) Apparent auxotrophy may result e.g. from a defective TRANSPORT SYSTEM; thus, e.g. an organism may appear to be an auxotroph if it is unable to take up a substrate which is necessary for the synthesis of an essential growth factor. (See also CRYPTIC MUTANT.) Isolation of auxotrophic mutants. Since auxotrophs have nutritional requirements in excess of those of the corresponding (prototrophic) wild-type strains, they cannot be isolated from mixed auxotroph–prototroph populations by common selective culture methods. In the limited enrichment method, a dilute suspension of mutagenized cells is inoculated onto a minimal medium which has been enriched with limiting amounts of nutrients; the dilution is chosen such that isolated colonies are obtained following incubation. Any auxotrophic cells which may be present form colonies which quickly exhaust the nutrient supply at their locations – so that colony size is restricted; a colony of prototrophic cells, which is not restricted by nutrient supply, attains a greater size. Thus, small colonies may be presumed to be those of auxotrophs. In the delayed enrichment method, the mutagenized preparation of cells is first inoculated onto a minimal medium. A small quantity of molten minimal agar is then layered onto the surface of the inoculated medium and allowed to set. The plate is then incubated. Colonies are formed only by prototrophs, and the positions occupied by these colonies are recorded. Finally, complete medium is layered onto the surface of the plate and allowed to set; the plate is then re-incubated. As nutrients diffuse into the minimal agar the auxotrophic cells begin to grow and form colonies. Auxotrophic mutants may also be isolated by a REPLICA PLATING process. Another method is based on the differing effects of PENICILLIN on growing and non-growing cells of certain (penicillinsensitive) organisms. If a well-washed mixture of auxotrophic and prototrophic cells is suspended in a minimal medium with an appropriate concentration of penicillin, the prototrophs are lysed while the auxotrophs, being unable to grow, remain viable. The suspension is then washed and is plated on a complete medium to recover the auxotrophs. In this method it is essential that the mutagenized cells be grown in a complete medium for several cell-division cycles prior to penicillin treatment. This is essential because the newly mutated cells contain the full complement of enzymes etc found in the prototroph; only after several rounds of cell division do the progeny cells exhibit a truly auxotrophic phenotype. Only low concentrations of cells should be used in this method since substances from the lysed cells may be used as nutrients by the auxotrophs – thereby rendering the latter susceptible to lysis by penicillin. (cf. STREPTOZOTOCIN.) auxotype See AUXANOGRAPHIC TECHNIQUE. avenacin A fluorescent polycyclic SAPONIN formed in the roots of oat plants (Avena spp). Avenacin confers resistance, in Avena spp, to many strains of Gaeumannomyces graminis (see TAKEALL); however, G. graminis var. avenae forms an extracellular glycosidase which detoxifies the compound. avermectins Macrolide-like antihelmintic agents, obtained from Streptomyces avermitilis, which are active against various human and animal parasites [AEM (2003) 69 1263–1269]. 63

aversion zone avian myeloblastosis virus See AVIAN ACUTE LEUKAEMIA VIRUSES and MYB. avian myeloblastosis virus reverse transcriptase See REVERSE TRANSCRIPTASE. avian myelocytomatosis virus See AVIAN ACUTE LEUKAEMIA VIRUSES. avian pneumoencephalitis Syn. NEWCASTLE DISEASE. avian reticuloendotheliosis viruses (REVs) A group of type C avian retroviruses of the ONCOVIRINAE. The group includes the replication-competent viruses duck infectious anaemia virus, Trager duck spleen necrosis virus and chicken syncytial virus, and the replication-defective, v-onc+ (v-rel + ) strain T virus (REV-T) and its associated helper virus (REAV, = REV-A). REVs are pathogenic in poultry (chickens, ducks, turkeys), causing a range of (usually rapidly lethal) diseases: e.g. anaemia, visceral reticuloendotheliosis, enlargement and necrosis of the spleen, lymphomas, and infiltrative nerve lesions. REV-T and its helper (REV-A) can be lethal in chickens within ca. 7–14 days of infection; the REV-A component has been reported to induce or activate a splenic suppressor cell population which inhibits the proliferation of cytotoxic cells capable of lysing REV-T-induced tumour cells [MS (1984) 1 107–112]. avian sarcoma viruses (ASVs) A group of v-onc+ type C retroviruses (subfamily ONCOVIRINAE) which, after a short latent period, cause tumours in fowl and (sometimes) other animals. The group includes ROUS SARCOMA VIRUS, Fujinami sarcoma virus (which carries v-fps), and Yamaguichi-73 sarcoma virus (which carries v-yes). (cf. FES.) avian tubercle bacillus Mycobacterium avium. avianized vaccine Any vaccine containing microorganisms whose virulence for a given host has been attenuated by adaptation in live chicks and/or serial passage through chick embryos (eggs). Attenuated organisms may or may not be inactivated prior to use in a vaccine. The FLURY VIRUS is an avianized strain. Avicel A commercial preparation consisting of ground microcrystalline (insoluble) CELLULOSE (average DP ca. 200); it is used e.g. for determining the ability of an organism or enzyme to degrade microcrystalline cellulose. (cf. CM-CELLULOSE.) avidin A protein (MWt ca. 68000) present e.g. in the white of raw hens’ eggs; the chicken avidin molecule consists of four identical subunits, and it can bind – non-covalently, but very strongly – four molecules of BIOTIN. (See also ABC IMMUNOPEROXIDASE METHOD; cf. STREPTAVIDIN.) avidity (immunol.) The stability of the antibody–antigen complex formed when multivalent antigen and homologous antiserum are mixed. Avidity depends not only on the AFFINITY of the individual determinant-combining site bonds but also on the number of satisfied valencies of the antigens and antibodies since, e.g., a complex in which two antigen molecules are linked by two antibody molecules is disproportionately more stable than a complex in which the two antigen molecules are linked by a single antibody molecule. Aviemore model See RECOMBINATION (figure 2). Avipoxvirus (fowlpox subgroup) A genus of viruses of the CHORDOPOXVIRINAE which infect birds (see e.g. FOWL POX). Avipoxviruses are commonly transmitted (mechanically) by arthropod vectors. Infected cells form lipid-rich A-type inclusion bodies; haemagglutinin is not formed. Infectivity is ether-resistant. Members are closely related serologically. Type species: fowlpox virus; other members include canarypox, juncopox, pigeonpox, quailpox, sparrowpox, starlingpox and turkeypox viruses. (See also POXVIRIDAE.) avirulence gene (avr gene) (plant pathol.) In a plant-pathogenic microorganism: a gene which interacts, functionally, with a

aversion zone (mycol.) A zone of growth inhibition separating two fungal colonies; such zones are formed e.g. when strains of Phycomyces blakesleeanus of similar mating type are cultured on the same plate. Aviadenovirus (avian adenoviruses) A genus of adenoviruses (family ADENOVIRIDAE) which infect birds; type species: fowl adenovirus type 1 (= chick embryo lethal orphan (CELO) virus, = gal-1). Diseases caused by aviadenoviruses include e.g. EGGDROP SYNDROME 1976, HAEMORRHAGIC ENTERITIS OF TURKEYS, INCLUSION BODY HEPATITIS, and MARBLE SPLEEN DISEASE. Several avian adenoviruses (including CELO virus) can induce tumours in newborn rodents (cf. MASTADENOVIRUS). avian acute leukaemia viruses (AcLVs) A group of replicationdefective, v-onc+ type C retroviruses (subfamily ONCOVIRINAE) which cause acute erythroid and myeloid leukaemias in chickens; they may also induce carcinomas, endotheliomas and sarcomas. AcLVs include avian myeloblastosis virus, AMV (which carries v-myb); avian erythroblastosis virus, AEV (which carries v-erb); and avian myelocytomatosis virus, MC29 (which carries v-myc). (See also ERB, MYB and MYC.) AcLV replication requires the presence of a replication-competent helper virus (see e.g. AVIAN LEUKOSIS VIRUSES). [Molecular biology of AcLVs: Book ref. 105, pp. 38–63.] avian encephalomyelitis (epidemic tremor) A POULTRY DISEASE caused by an ENTEROVIRUS; infection in adult birds is usually asymptomatic, but in young chicks symptoms may include ataxia, tremors and somnolence. Infection occurs e.g. by ingestion of food contaminated with faeces from infected birds; transmission can also occur via the egg. avian erythroblastosis virus See AVIAN ACUTE LEUKAEMIA VIRUSES. avian infectious bronchitis An acute, highly infectious POULTRY DISEASE caused by a coronavirus (IBV – see CORONAVIRIDAE). The symptoms include gasping, coughing, nasal discharge, etc; mortality rates may be high. Secondary bacterial infection may be common. [Experimentally-produced disease with mixed IBV/Escherichia coli infection: JGV (1985) 66 777–786.] Live vaccines are available. A strain of the avian infectious bronchitis virus (the ‘T’ strain) may cause avian kidney disease (Cummings’ disease). avian infectious laryngotracheitis An acute POULTRY DISEASE, affecting mainly chickens and pheasants, caused by gallid herpesvirus 3. Mortality rates may be high. avian leukosis complex A group of POULTRY DISEASES which includes e.g. LYMPHOID LEUKOSIS and MAREK’S DISEASE. avian leukosis viruses (ALVs; lymphatic leukosis viruses; lymphatic leukaemia viruses) A group of avian type C retroviruses (subfamily ONCOVIRINAE) which usually induce neoplastic disease only after a long latent period (several months or more). The most common neoplasm induced is LYMPHOID LEUKOSIS. (See also OSTEOPETROSIS.) ALVs are replication-competent and v-onc− (see RETROVIRIDAE). In some cases induction of neoplastic disease may involve the insertion of a viral LTR adjacent to and upstream of a c-onc (usually c-myc) sequence, the LTR acting as a promoter for c-onc expression; alternatively, or perhaps additionally, an LTR may have a promoter-unrelated transcription-enhancing function [Book ref. 105, pp. 64–68]. Neoplastic transformation may require the activation of a second cellular gene, B-lym, in addition to c-myc. ALVs often occur in association with replication-defective vonc+ viruses (e.g. AVIAN ACUTE LEUKAEMIA VIRUSES) as ‘helper’ or ‘associated’ viruses; such ALVs include Rous-associated viruses (RAVs) and myeloblastosis-associated viruses (MAVs). 64

azole antifungal agents specific ‘resistance gene’ in certain strain(s) of the host species, eliciting a defensive response (HYPERSENSITIVITY) which results in resistance to that particular strain of the pathogen. The products of such genes appear to be delivered to the interior of plant cells via a type III PROTEIN SECRETION system (designated Hrp: hypersensitivity response and pathogenicity) [see e.g. JB (1997) 179 5655–5662]; under in vitro conditions, the Hrp system in Pseudomonas syringae pv. tomato has been found to include a filamentous pilus, 6–8 nm in diameter, in which HrpA is a major structural protein [PNAS (1997) 94 3459–3464]. (See also HOP PROTEINS.) Avirulence genes form part of the ‘gene-for-gene’ concept that relates to interaction between plants and their pathogens [ARPpath. (1971) 9 275–296]. [Gene-for-gene complementarity in plant–pathogen interactions: ARG (1990) 24 447–463.] Direct interaction between the products of a resistance gene and an avirulence gene has been reported to occur, for example, when strains of rice expressing the Pi-ta resistance gene are challenged with strains of the rice pathogen Magnaporthe grisea (= Pyricularia oryzae) that express AVR-Pita; against this challenge, the plant failed to succumb to rice BLAST DISEASE [EMBO (2000) 19 4004–4014]. Avirulence genes from Pseudomonas syringae commonly have a GC% of ∼40–50, i.e. markedly below the chromosomal values (59–61) typical of the species; such a difference in GC% – also commonly seen between PATHOGENICITY ISLANDS and their host chromosomes – is consistent with the concept of horizontal transfer of these genes. Also consistent with horizontal transfer is the finding of highly conserved sequences flanking avirulence genes in P. syringae pv. pisi [Microbiology (2001) 147 1171–1182]. (See also HARPIN.) avirulent Not exhibiting VIRULENCE. avocado sunblotch viroid See VIROID. avoiding reaction Syn. PHOBIC RESPONSE. avoparcin A glycopeptide antibiotic, produced by Streptomyces candidus, which inhibits Gram-positive bacteria by interfering with peptidoglycan synthesis (see VANCOMYCIN); it is a wellestablished FEED ADDITIVE for pigs and poultry, and has been found to have growth-promoting properties for ruminants. In sheep, avoparcin appears to shift the balance of cellulolytic bacteria from ruminococci to Bacteroides succinogenes [JGM (1985) 131 427–435]. avr gene (plant pathol.) See AVIRULENCE GENE. aw Symbol for WATER ACTIVITY. axenic Of a culture: containing or comprising cells of a single species. Thus, e.g., an axenic bacterial culture is a pure (uncontaminated) culture of a single species or strain, while an axenic tissue culture is one which contains cells (of one or more types) from one species (or individual) with no microbial contaminants, intracellular parasites, viruses etc. Certain microorganisms – e.g. obligately intracellular bacteria, obligately predatory protozoa – cannot be grown axenically. axial fibrils See SPIROCHAETALES. axial filament (1) See ENDOSPORE (bacterial). (2) See SPIROCHAETALES. (3) See AXOPODIUM. axile Situated in the centre or on the axis. axoneme (1) See FLAGELLUM (b). (2) See AXOPODIUM. axopodium A fine, rod-like, often tapering, relatively rigid type of PSEUDOPODIUM which has an axial core of microtubules (the axial filament, axial rod or axoneme). Axopodia occur e.g. in HELIOZOEA and RADIOLARIA in which they typically emanate radially from the cell body. They function mainly in feeding

(but see HELIOZOEA). When an axopodium comes into contact with a prey organism, it adheres to it and may – at least in some cases – immobilize it; the axopodia of some heliozoa have extrusomes (kinetocysts) which may function in immobilizing prey. Ingestion may involve the retraction of the axopodium with the prey, and/or a co-operative engulfing action of a number of pseudopodia in the vicinity. axostyle A rod-like endoskeletal structure which occurs in some protozoa (e.g. Giardia, Hexamita, Trichomonas); in Trichomonas it extends from the anterior end of the cell and projects a short distance beyond the posterior end. (cf. COSTA; see also OXYMONADIDA.) azaserine (CO2 H.CHNH2 .CH2 .O.CO.CH=NH+ =N− ) An ANTIBIOTIC and antitumour agent obtained from Streptomyces sp. It is an analogue of glutamine and blocks a number of reactions in which glutamine acts as an NH2 donor; in particular, it binds to and inactivates phosphoribosylformylglycinamidine synthetase, thus preventing purine (and hence nucleotide) synthesis (see Appendix V(a)). (cf. DON; HADACIDIN.) azathioprine See IMMUNOSUPPRESSION. azdimycin See POLYENE ANTIBIOTICS (b). azide (N3 − ) Azide acts e.g. as a RESPIRATORY INHIBITOR by combining with, and preventing the reduction of, oxidized CYTOCHROME OXIDASES of the aa3 -type. Sodium azide (NaN3 ) is an antimicrobial agent used e.g. as a preservative in some laboratory reagents (0.1% final concentration NaN3 ). It is also used e.g. in certain selective media (0.025% w/v NaN3 ) for the isolation of enterococci from samples of sewage-polluted water; at this concentration coliforms and many other Gram-negative bacteria are inhibited. 3′ -azido-3′ -deoxythymidine See AZT. azithromycin A MACROLIDE ANTIBIOTIC used e.g. as an alternative to clarithromycin in the prophylaxis and treatment of infections involving members of the M. avium complex (see MAC). The drug tends to concentrate in macrophages and tissue cells. Strains resistant to azithromycin are also resistant to clarithromycin. Side-effects are uncommon; they include nausea, diarrhoea, headaches, dizziness, deafness. (See also QUORUM SENSING.) azlocillin See PENICILLINS. AZM Adoral zone of membranelles: a number of MEMBRANELLES serially arranged in a definite and taxonomically important pattern along the left-hand side of the oral area in many members of the OLIGOHYMENOPHOREA and POLYHYMENOPHOREA; the corresponding ciliature in peritrichs and spirotrichs is sometimes called the adoral ciliary spiral. The AZM is primarily concerned with feeding (i.e., the production of water currents directed towards the cytostome) but is sometimes used also for locomotion. (cf. PARORAL MEMBRANE.) Azoarcus See SPLIT GENE (e). azofer See NITROGENASE. azofermo See NITROGENASE. azoferredoxin See NITROGENASE. azole antifungal agents A group of synthetic, broad-spectrum ANTIFUNGAL AGENTS, many of which are useful in the treatment of mycoses in man and animals while others are effective against many fungal diseases of plants. The group contains two main categories: the imidazole derivatives (e.g. the agriculturally useful BENZIMIDAZOLES and the medical and veterinary drugs bifonazole, butoconazole, CLOTRIMAZOLE, econazole, fenticonazole, isoconazole, KETOCONAZOLE, MICONAZOLE, oxiconazole, sulconazole, TIOCONAZOLE, and zinconazole) and the triazole derivatives (e.g. the agricultural antifungals FLUTRIAFOL, PROPICONAZOLE, TRIADIMEFON, and TRIADIMENOL, and the medical drugs ITRACONAZOLE, terconazole and vibunazole). Most of the medically 65

Azolla wavelength) are also formed during growth on solid media at 30° C. Enlarged, ovoid or pleomorphic, non-motile, capsulated forms (‘C forms’) may develop under certain conditions (e.g. in old cultures). Metabolism is mainly respiratory, with either oxygen or NO3 − acting as terminal electron acceptor; DENITRIFICATION occurs under microaerobic conditions. Glucose or fructose may be fermented weakly. Disaccharides are not metabolized. Oxidase +ve; catalase variable; phosphatase +ve; indole −ve; weakly pectinolytic. Optimum growth temperature: 35–37° C. Colonies on potato agar are typically pink, often wrinkled, not slimy. NITROGEN FIXATION occurs under microaerobic conditions; an ‘uptake hydrogenase’ (see NITROGENASE) is present, and A. lipoferum (but not A. brasilense) can grow as an H2 -dependent lithoautotroph. Aerobic growth can also occur in the presence of fixed nitrogen (e.g. NH4 + , NO3 − ). GC%: 69–71. Type species: A. lipoferum (formerly Spirillum lipoferum). [Book ref. 22, pp. 94–104.] Azospirilla occur in soil, both free-living and in association with the roots of grasses (including cereals) and tuberous plants; the bacteria occur on the root surface, in the mucigel, and also within the tissues of the root (outer and inner cortex and stele). The plant appears to benefit from the nitrogen fixed by the bacteria; nodule formation does not occur (cf. ROOT NODULES). There is some degree of host specificity: ‘C4 plants’ (e.g. maize) are infected by A. lipoferum, ‘C3 plants’ (e.g. barley, oats, rice, rye, wheat) by strains of A. brasilense. Azotobacter A genus of Gram-negative, CYST-forming bacteria (family AZOTOBACTERACEAE) which occur e.g. in fertile soils of near-neutral pH. The cells are peritrichously flagellated or nonmotile, and are commonly short rods or coccobacilli – though A. paspali regularly forms both rods and long filaments; the organisms appear to contain many copies of the chromosome per cell [JGM (1984) 130 1603–1612]. Carbon sources used by all species include e.g. glucose, fructose, sucrose, acetate, fumarate, gluconate, and ethanol; most species can use nitrate and/or ammonium salts as a source of nitrogen. In the presence of combined nitrogen growth can occur within the pH range ca. 5–8.5; NITROGEN FIXATION occurs optimally within the pH range 7–7.5. In laboratory cultures nitrogen-fixing ability declines with age, and is very poor immediately prior to encystment. (Cyst-formation occurs maximally in old cultures on nitrogenfree media containing 0.2% butanol.) The optimum growth temperature varies with species, and is ca. 30–37° C. GC%: ca. 63–68. Type species: A. chroococcum. A. armeniacus. Peritrichously flagellated. Can use e.g. caprylate and mannitol but not e.g. caproate; some strains can use propionate. A. beijerinckii. Non-motile. Can use e.g. malonate and propionate but not caproate or rhamnose. A. chroococcum. Peritrichously flaggellated. Can use e.g. caproate, mannitol and propionate, but not e.g. caprylate. A. nigricans. Non-motile. Cannot use caproate, propionate or rhamnose. Some strains form e.g. a yellow or dark non-diffusible pigment or a dark diffusible pigment. A. paspali. Peritrichously flagellated. Cannot use caproate, caprylate, malonate, mannitol, propionate or rhamnose, but can use oxaloacetate, and some strains can use propan-1-ol. Appears to occur only on (or within?) the root cortex of the grass Paspalum notatum. A. vinelandii. Peritrichously flagellated; non-motile strains have been reported. Can use caproate, caprylate, malonate,

useful azoles are administered topically, being poorly absorbed from the gut and/or too toxic for systemic use; however, a few (e.g. ketoconazole, itraconazole and vibunazole) can be given orally. With the exception of the BENZIMIDAZOLES, the azoles generally appear to have the same primary mode of action. At minimal fungistatic concentrations they interfere with the permeability and function of the CYTOPLASMIC MEMBRANE by inhibiting the biosynthesis of ergosterol. In the normal biosynthetic pathway ergosterol is synthesized from its precursor lanosterol by a 14a-demethylation reaction which involves a cytochrome P-450dependent monooxygenation step; the azole compound binds (in place of oxygen) to the 6th coordination position of the P-450 haem iron, thus preventing the monooxygenation step. As a result, 14a-methylated sterols accumulate and ergosterol (and cholesterol) levels fall; this not only alters membrane permeability: the altered lipid environment of the membrane also interferes with the activity and/or control of other enzyme systems (e.g. chitin synthase). Miconazole – in addition to its effect on the cytoplasmic membrane – also exerts an apparently direct inhibitory effect on the mitochondrial ATPase in yeasts such as Candida albicans and Saccharomyces cerevisiae [Eur. J. Bioch. (1984) 143 273–276]. Actively growing fungi exposed to minimal fungistatic concentrations of azoles (e.g. 10−8 –10−7 M for miconazole) show characteristic structural changes, including the formation of dense membrane-derived vesicles at the cell periphery. At somewhat higher fungistatic concentrations (e.g. 10−6 M miconazole) changes in the cell vacuole also occur, the vacuole becoming filled with vesicles and granular material. At still higher concentrations (e.g. 10−5 M miconazole) the azoles become fungicidal, causing degeneration of organelles (mitochondria and nuclei). [Review of medically useful azoles: Book ref. 153, pp. 133– 153.] Azolla See ANABAENA. Azomonas A genus of Gram-negative or (A. macrocytogenes) Gram-variable, motile bacteria (family AZOTOBACTERACEAE) which occur e.g. in soil and water. Cysts are not formed (cf. AZOTOBACTER). Most strains form water-soluble pigments, but none forms insoluble pigments; a fluorescent pigment is formed by some strains in iron-deficient media. Carbon sources used by all species include e.g. fructose, glucose, acetate, fumarate, lactate, and ethanol; all species can fix nitrogen and can use ammonium salts as the sole source of nitrogen. Optimum growth temperature: 30–37° C, according to species. GC%: ca. 52–59. Type species: A. agilis. A. agilis. Peritrichously flagellated. Can use e.g. malonate, but not mannitol. Growth can occur at 32° C and 37° C. A. insignis. Lophotrichously flagellated. Can use e.g. malonate, but not mannitol. Growth can occur at 32° C but not at 37° C. A. macrocytogenes. Monotrichously flagellated (rarely biflagellated at one pole). Can use mannitol and maltose, but not malonate. [Book ref. 22, pp. 230–234.] azomycin See NITROIMIDAZOLES. Azorhizobium caulinodans See NITROGEN FIXATION. Azospirillum A genus of Gram-negative or Gram-variable, asporogenous, nitrogen-fixing bacteria. Cells: curved and straight rods, often with pointed ends, ca. 1.0 × 2.1–3.8 µm. Motile by a single polar flagellum; numerous lateral flagella (of shorter

66

azygospore drugs (e.g. PROBENECID) that inhibit glucuronidation may therefore affect the plasma concentration of AZT. The use of AZT is associated with megaloblastic changes; the drug may induce a dose-dependent macrocytic anaemia (less often a severe normocytic anaemia) and is also able to induce neutropenia [haematological aspects of HIV infection: BCH (2000) 13 215–230]. The value of AZT in anti-AIDS combination drug therapy (against HIV-1) was indicated by an in vitro study in which those nucleoside reverse transcriptase inhibitors which lacked the 3′ -azido moiety were less active against a particular mutant form of the reverse transcriptase [AAC (2005) 49 1139–1144]. azthreonam Syn. AZTREONAM. aztreonam (azthreonam) A MONOBACTAM derivative in which R′ = an aminothiazoleoxime group, R′′ = H, R′′′ = CH3 , R′′′′ = SO3 − K+ (see b-LACTAM ANTIBIOTICS). It is active only against aerobic Gram-negative bacteria, having a high degree of specificity for PBP3 of Gram-negative bacteria (see PENICILLINBINDING PROTEINS); it is resistant to most b-lactamases. [Action, use: Drugs (1986) 31 96–130.] Azuki bean mosaic virus See POTYVIRUSES. azure See polychrome METHYLENE BLUE. azurin (1) A BLUE PROTEIN which occurs in certain bacteria (e.g. Alcaligenes denitrificans, Bordetella pertussis, Paracoccus denitrificans, Pseudomonas aeruginosa); depending on source, the MWt ranges from ca. 12000 to ca. 15000, and the Em appears to be in the approximate range 230–330 mV. (2) A solution of CuSO4 and NH4 OH used as an agricultural antifungal agent. azygospore A parthenogenically derived spore, similar to a ZYGOSPORE, formed e.g. by many species of the Mucorales.

mannitol, propionate and rhamnose. A yellowish-green watersoluble fluorescent pigment is formed on iron-deficient media. [Book ref. 22, pp. 220–229.] Azotobacteraceae A family of Gram-negative (or Gramvariable), aerobic, chemoorganotrophic bacteria which occur in soil, in the rhizosphere, and in aquatic habitats; the organisms are capable of NITROGEN FIXATION – typically under free-living conditions, but sometimes in association with higher plants. Cells: ovoid, or round-ended rods (sometimes filaments), 1.5–2.0 µm or more in width, which may be motile (polarly or peritrichously flagellated) or non-motile; some species form cysts. Pigments, some fluorescent, are formed by some species. PHB can be accumulated. Catalase +ve. Oxidase +ve (most strains of most species). GC%: ca. 52–68. Two genera: AZOMONAS, AZOTOBACTER. [Book ref. 22, pp. 219–234.] azotoflavin See FLAVODOXINS. AZT (3′ -azido-3′ -deoxythymidine; zidovudine) A thymidine analogue ANTIRETROVIRAL AGENT used in the treatment of AIDS. AZT is converted by cellular enzymes to the triphosphate derivative which is then incorporated – instead of thymidine – into (provirus) DNA by the viral REVERSE TRANSCRIPTASE (see RETROVIRIDAE); the presence of the 3′ -azido group inhibits further chain elongation by preventing the formation of a phosphodiester bond at the 3′ position. Cellular DNA polymerase a is much less sensitive than reverse transcriptase to AZT triphosphate. AZT competes for intracellular phosphorylation with another NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR, stavudine. As high-level resistance develops readily if AZT is used alone, it is used in combination with other drugs. Unlike other nucleoside reverse transcriptase inhibitors, AZT undergoes significant metabolism (glucuronidation) in the liver;

1. Words in SMALL CAPITALS are cross-references to separate entries. 2. Keys to journal title abbreviations and Book ref. numbers are given at the end of the Dictionary. 3. The Greek alphabet is given in Appendix VI. 4. For further information see ‘Notes for the User’ at the front of the Dictionary.

67

Dictionary of Microbiology and Molecular Biology, Third Edition Paul Singleton and Diana Sainsbury © 2006 John Wiley & Sons Ltd. ISBN: 0-470-03545-5

B No further development of the B cell occurs unless it encounters specific antigen e.g. within so-called germinal centres in the spleen or lymph nodes. In the event of contact with specific antigen, the outcome depends e.g. on the type of antigen involved and the contribution of T cells: see ANTIBODY FORMATION. When a B cell is appropriately stimulated it prepares for the role of antibody formation by initially undergoing BLAST TRANSFORMATION and then proliferating to form a clone of cells of identical antigenic specificity (= clonal expansion); some of these cells develop as PLASMA CELLS while others (commonly) become MEMORY CELLS. B cells which do not bind specific antigen remain viable for a limited period of time and subsequently undergo APOPTOSIS. B-tubule (B-subfibre) See FLAGELLUM (b). B-type inclusion body See POXVIRIDAE. B-type particles See TYPE B ONCOVIRUS GROUP. B-type starter See LACTIC ACID STARTERS. B virus (cercopithecine herpesvirus 1; cercopithecid herpesvirus 1; herpesvirus B; Herpesvirus simiae) A herpesvirus (subfamily ALPHAHERPESVIRINAE) which naturally infects monkeys of the genus Macaca. In rhesus monkeys (M. mulatta) infection may be asymptomatic, or vesicular lesions (which may ulcerate) may develop in the mouth and sometimes on the skin and conjunctivae. B virus may be transmitted to humans e.g. by monkey bites or scratches, and can cause in humans a severe (usually fatal) encephalomyelitis (‘monkey-bite encephalomyelitis’). B12 coenzymes See VITAMIN B12 . B19 parvovirus See ERYTHROVIRUS. B663 CLOFAZIMINE. Babes–Ernst granules METACHROMATIC GRANULES observed in bacteria. Babesia A genus of protozoa (subclass PIROPLASMASINA) parasitic in invertebrates and in the erythrocytes (RBCs) of vertebrates (cf. THEILERIA); at least some species (including B. equi and B. microti ) develop in the lymphocytes (as well as in the RBCs) of the vertebrate host, and it has been suggested that such species be transferred to other genera (e.g. Nicollia, Nuttallia). Some species (e.g. B. bigemina, B. bovis) can cause tick-borne disease in domestic animals (see REDWATER FEVER), and some (e.g. B. divergens, B. microti ) can cause disease in man [ARE (1981) 26 90–92]. The cells of Babesia are rounded or pyriform, ca. 1–6 µm. In the typical life cycle, sporozoites of Babesia are injected into the vertebrate host by the tick vector, and each sporozoite enters an RBC and undergoes schizogony to form two or four merozoites – which infect fresh RBCs when the host cell ruptures. Following the tick’s meal of infected blood, gametes are formed in the tick’s gut, and these fuse and give rise to a (motile) kinete which passes, via various tissues, to the salivary glands – there undergoing sporogony and forming many sporozoites. Unlike Theileria, Babesia can invade the ovary and egg of the tick, and can be transmitted transovarially to the tick’s offspring. [Life cycles of Babesia and Theileria: AP (1984) 23 37–103.] babesiosis Any disease of man or animals caused by a species of BABESIA (e.g. REDWATER FEVER). Bacillaria See DIATOMS. Bacillariophyta See DIATOMS. bacillary angiomatosis See BARTONELLA.

B cell (immunol.) Syn. B LYMPHOCYTE. B cell differentiation factor See LYMPHOKINES. B cell growth factor See LYMPHOKINES. B cell superantigen See SUPERANTIGEN. B-DNA See DNA. B lymphocyte (B cell) A type of LYMPHOCYTE concerned primarily with ANTIBODY FORMATION (cf. T LYMPHOCYTE). In mammals, B cells are formed initially in the fetal liver, but later they develop from haemopoietic stem cells in the bone marrow. (In birds, B cells appear to develop in the BURSA OF FABRICIUS.) B cells occur e.g. in blood, in lymph and in the spleen. In an adult, the B cell population consists of >106 clones, the cells of each clone being potential sources of antibodies with a unique and highly specific antigen-binding capacity. In mammals, B cells mature in a series of stages. Stem cells give rise to pro-B cells which, in turn, develop as pre-B cells. Pre-B cells differ from mature B cells e.g. in that they express no surface immunoglobulin (Ig), i.e. they are sIg− , although they contain mu HEAVY CHAINS (associated with so-called surrogate light chains) which may be located at the cell surface. The next stage, the immature B cell, is characterized by the presence of monomeric IgM at the cell surface; interaction with specific antigen at this stage may lead to inactivation of the cell. The mature B cell displays IgM and IgD at the cell surface (with antigen-binding sites facing outwards); the IgM and IgD have identical antigenic specificity. The B cell reaches maturity, in an antigen-independent way, within the bone marrow. In addition to antibodies, the surface of a mature B cell displays various types of molecule involved in the recognition of exogenous factors and the initiation of intracellular signalling. These molecules include: (i) a receptor that mediates isotype switching (= class switching – e.g. the IgM → IgG switch following antigenic stimulation) (see CD40); (ii) MHC class II molecules (required for presenting antigen to a T cell: see ANTIBODY FORMATION); (iii) co-stimulatory molecules (designated B7.1 and B7.2) which, during B cell–T cell contact, bind to a specific T cell receptor and initiate signals that activate the T cell (see CD28); (iv) CD32: a low-affinity receptor for the Fc portion of IgG (the binding of antigen-bound antibody to CD32 may suppress the ongoing production of specific antibodies); (v) CD21 (involved in B cell activation, and a binding site for certain components of COMPLEMENT); (vi) receptors for CYTOKINES (including INTERLEUKIN-1; INTERLEUKIN-4, which e.g. induces isotype switching and promotes expression of MHC class II molecules on B cells; and INTERLEUKIN-6). The body’s B cell population can be divided into three subsets on the basis of the CD5 and CD23 antigens. B cells in the general circulation are mainly CD5− , CD23+ ; they have a relatively short existence and are continually renewed from the bone marrow stem cells. Two other subsets, one CD5+ , CD23− , and the other CD5− , CD23− , are found mainly in mucosal sites (e.g. the peritoneal cavity) and are self-renewing (albeit with precursor cells in the bone marrow); these cells can rapidly produce IgM antibodies (of a limited range of specificities) in response to bacterial polysaccharides, and can do so without help from T cells. These two populations of B cells are viewed as a first line of defence against bacterial incursion in sites which are particularly vulnerable to infection. 68

Bacillus bacillary dysentery See DYSENTERY (a). bacillary white diarrhoea Syn. PULLORUM DISEASE. bacille Calmette–Gu´erin See BCG. bacillin Syn. BACILYSIN. bacillus (1) A member of the genus BACILLUS. (2) Any rodshaped bacterial cell, i.e., a cell whose length is ca. two or more times greater than its width. (cf. COCCOBACILLUS and FILAMENT.) A bacillus may be straight or curved (cf. VIBRIO sense 2), with rounded, truncated or tapered ends (cf. FUSIFORM), and may occur singly, in groups, pairs, chains, etc. (See also PALISADE.) Bacillus A genus of GRAM TYPE-positive, strictly aerobic or facultatively anaerobic, typically catalase-positive, rod-shaped, ENDOSPORE-forming bacteria. The organisms typically occur as saprotrophs in soil and water, but certain species can be pathogenic in man and other mammals (see e.g. B. anthracis and B. cereus, below) and some species are entomopathogenic (see e.g. B. moritai, B. popilliae and B. thuringiensis). [Insecticidal species: Book ref. 171, pp. 185–209; MR (1986) 50 1–24.] Bacillus spp can cause biodeterioration (see e.g. FLAT SOUR, LEATHER SPOILAGE, SWELL), but some species are used commercially as sources of antibiotics (see e.g. BACITRACIN, POLYMYXINS) or other products (e.g. DEBRANCHING ENZYMES, GLUCOSE ISOMERASE, GLYCEROKINASE, SUBTILISINS). Cells: typically motile rods, commonly ca. 0.5–1.5 × 2–6 µm, often in chains; some strains form a CAPSULE, and some are pigmented. (See also S LAYER and TEICHOIC ACIDS.) Metabolism may be respiratory (see RESPIRATION) – some strains being capable of NITRATE RESPIRATION – or facultatively fermentative (see FERMENTATION); a few species (e.g. B. macerans, B. polymyxa) can carry out NITROGEN FIXATION. Most species are chemoorganoheterotrophs; B. schlegelii can grow chemolithoautotrophically (see CARBOXYDOBACTERIA). Utilizable substrates for organoheterotrophic species range from simple sugars and other carbohydrates to e.g. uric acid (see B. fastidiosus) and proteinaceous materials; PENTOSES are metabolized via the HEXOSE MONOPHOSPHATE PATHWAY. Many species can grow on NUTRIENT AGAR. Storage compounds include e.g. POLY-b-HYDROXYBUTYRATE. The genus includes psychrotrophs (e.g. B. globisporus), thermophiles (e.g. B. schlegelii, B. stearothermophilus) and alkalophiles (e.g. B. alcalophilus, B. firmus). GC%: ca. 30–70. Type species: B. subtilis. B. alcalophilus. An ALKALOPHILE (q.v.): optimum growth pH ca. 9–10; no growth below pH 7. B. alvei. See EUROPEAN FOULBROOD. B. amyloliquefaciens. Similar or identical to B. subtilis. (See also AMYLASES.) B. amylolyticus. Nom. rev. [IJSB (1984) 34 224–226]. B. aneurinolyticus. A species, related to B. brevis, which produces a thiaminase. (See also BACTERIOPHAGE fBA1.) B. anthracis. The causal agent of ANTHRAX. Cells: nonmotile, ca. 1.5 × 3–6 µm, typically square-ended and usually in chains. Virulent strains form a PLASMID-encoded toxin (see ANTHRAX TOXIN) and a plasmid-encoded poly-D-glutamic acid CAPSULE. [Capsule-encoding plasmid: see e.g. Inf. Immun. (1985) 49 291–297.] (cf. STERNE STRAIN.) Growth occurs on nutrient agar. In biochemical tests B. anthracis gives results very similar to those of B. cereus. Lecithinase activity is weak or absent. Haemolysis on sheep-blood agar is weak or absent. B. anthracis is susceptible to the ‘g phage’ (B. cereus is not). On agar containing benzylpenicillin (0.05–0.5 unit/ml) B. anthracis gives rise to chains of enlarged, spherical cells (‘string of pearls’ effect). B. azotofixans. A proposed (nitrogen-fixing) species from Brazilian soil [IJSB (1984) 34 451–456].

B. badius. Similar to B. brevis. Growth is not inhibited by 5% NaCl. The (ellipsoidal) spore does not distend the cell. B. brevis. Typically forms no acid or gas from carbohydrates. Growth occurs at 50° C. Spore: ellipsoidal, distending the cell. (See also TYROCIDINS.) ‘B. caldolyticus group’. Strains (including B. caldotenax and B. caldovelox ) closely related to B. stearothermophilus. B. cereus. A saprotroph or opportunist pathogen which can cause FOOD POISONING (q.v.) or, rarely, e.g. meningitis. [Meningitis due to B. cereus, and review of Bacillus infections other than anthrax: Israel J. Med. Sci. (1983) 19 546–551.] Cells: typically motile rods (mean width ca. 1.5 µm), sometimes pigmented. Spore: ellipsoidal, not distending the cell. Acid is formed in anaerobic glucose broth; no acid is formed from arabinose, mannitol or xylose. No gas is formed from carbohydrates. Most strains are VP +ve. Starch and casein are hydrolysed, and lecithinases are produced. Nitrate is reduced by most strains. No growth at 50° C. B. circulans. Similar to B. polymyxa but ferments carbohydrates anaerogenically; typically, a range of carbohydrates is fermented. (See also MOTILE COLONIES.) B. coagulans. Forms lactic acid as the major product of glucose fermentation; 2,3-butanediol is also produced. No gas is formed from carbohydrates. VP +ve. (See also GLUCOSE ISOMERASE.) B. euloomarahae. See MILKY DISEASE. B. fastidiosus. Obligately aerobic. Uses uric acid as a source of carbon, nitrogen and energy. B. firmus. An ALKALOPHILE. Forms acid from glucose but typically from few other carbohydrates. B. fribourgensis. See MILKY DISEASE. B. globisporus. A PSYCHROTROPH (maximum growth temperature ca. 25–30° C). Urease +ve. Spore: round, distending the cell. B. larvae. See AMERICAN FOULBROOD. B. lautus. Nom. rev. [IJSB (1984) 34 224–226]. B. lentimorbus. See MILKY DISEASE. B. licheniformis. Morphologically and biochemically similar to B. subtilis, but growth readily occurs anaerobically (see also DENITRIFYING BACTERIA). B. macerans. Biochemically very similar to B. polymyxa. Forms SCHARDINGER DEXTRINS. B. megaterium. Cell width commonly ca. 1.5 µm but may reach ca. 3.0 µm in carbohydrate-containing media. Spore: ellipsoidal, not distending the cell. Glucose and many other carbohydrates are utilized anaerogenically. B. moritai. A species pathogenic e.g. in house-flies. The addition of B. moritai spores to faeces has been found to reduce the emergence of adult house-flies by up to ca. 90%. B. mycoides. Morphologically and biochemically very similar to B. cereus. Often regarded as a non-motile variety of B. cereus. B. pabuli. Nom. rev. [IJSB (1984) 34 224–226]. B. pasteurii. An ALKALOPHILE (optimum growth at ca. pH 9). Cells: typically slender (ca. 0.5–1.0 µm wide). Spore: spherical, typically distending the cell. Carbohydrates are attacked either very weakly or not at all. Urease +ve. NH3 is needed for growth. ‘B. piliformis’. See TYZZER’S DISEASE. B. polymyxa. Cells: typically slender (ca. 0.5–1.0 µm wide); usually motile. Spore: ellipsoidal, distending the cell. Grows well anaerobically, and produces acid and gas from carbohydrates; typically, glucose, mannitol, and many other sugars and sugar alcohols are utilized. Glucose is fermented via the BUTANEDIOL FERMENTATION. Most strains attack e.g. casein, gelatin, starch 69

bacillus Calmette–Gu´erin and pectins, and most can carry out NITROGEN FIXATION. (See also POLYMYXINS.) B. popilliae. See MILKY DISEASE. B. psychrophilus. A proposed (psychrophilic) species [IJSB (1984) 34 121–123]. B. pulvifaciens. Proposed species (isolated from a diseased bee) [IJSB (1984) 34 410–413]. B. pumilus. Cells: typically slender (0.5–1.0 µm wide); usually motile. Spore: elongated, not distending the cell. Metabolically similar to B. subtilis, but starch is not utilized. Usually VP +ve. B. schlegelii. See CARBOXYDOBACTERIA and HYDROGEN-OXIDIZING BACTERIA. B. sphaericus. Cells: slender (ca. 0.5–1.0 µm wide); usually motile. Spore: spherical, distending the cell. Typically, carbohydrates are not utilized. Can cause LEATHER SPOILAGE, and can be insecticidal to e.g. mosquito larvae – toxicity apparently being due to an uncharacterized toxin and not associated with sporulation. [Field evaluation of a B. sphaericus strain as a mosquito ‘biocide’: J. Inv. Path. (1986) 48 133–138.] B. stearothermophilus. Thermophilic; can grow at e.g. 65° C. Cells: ca. 1.0 µm wide; spore: ellipsoidal, often distending the cell. The spores are highly resistant to heat, and are sometimes used to monitor AUTOCLAVE performance. (See also FLAT SOUR.) Typically, a range of carbohydrates can be metabolized anaerobically and anaerogenically; the main product of carbohydrate fermentation commonly appears to be lactic acid. (See also GLYCEROKINASE.) B. subtilis. Cells: slender (typically ca. 0.8 µm wide), usually motile; chains are uncommon. (See also CERULENIN and MACROFIBRE.) Spore: ellipsoidal, usually not distending the cell. Metabolism appears to be primarily respiratory. Growth does not occur in anaerobic glucose broth. Glucose, various other sugars and sugar alcohols, and starch, are metabolized anaerogenically. VP +ve. Nitrate is reduced. Casein and gelatin are hydrolysed. Phages which infect B. subtilis include e.g. BACTERIOPHAGE PBS1, BACTERIOPHAGE f105 and BACTERIOPHAGE SPO1. B. thuringiensis. An entomopathogenic species which is morphologically and biochemically very similar to B. cereus, differing primarily in its formation of DELTA ENDOTOXIN (q.v.). B. validus. Nom. rev. [IJSB (1984) 34 224–226]. Other species include e.g. B. insolitus, B. laterosporus, B. lentus, and B. pantothenticus. Note on the identification of species. Some mutually contradictory tables of biochemical test reactions have been published. For example, the VP test reactions (obtained using traditional methods) given in Book ref. 46, p. 1731 differ significantly, in respect of a number of species, from those (obtained using the API system) given in JGM (1984) 130 1871–1882. (Species designated as ‘VP +ve’ above are confirmed as such in many sources.) bacillus Calmette–Gu´erin See BCG. bacilysin (‘bacillin’; ‘tetaine’) A dipeptide ANTIBIOTIC which is active against a wide range of Gram-positive and Gramnegative bacteria and e.g. against Candida albicans. It consists of a C-terminal epoxy-L-amino acid (‘anticapsin’) and an Nterminal L-alanine residue; it is taken up by peptide transport systems in sensitive cells, and is subsequently hydrolysed by cellular enzymes to release the anticapsin – an inhibitor of glucosamine (and hence e.g. PEPTIDOGLYCAN) synthesis. (cf. WARHEAD DELIVERY.) bacitracin A cyclic dodecapeptide ANTIBIOTIC produced by strains of Bacillus spp. It is active against many Grampositive and certain Gram-negative bacteria (e.g. Neisseria spp,

Haemophilus spp). In the presence of divalent cations (particularly Zn2+ ) bacitracin binds to bactoprenol pyrophosphate, inhibiting the regeneration of bactoprenol monophosphate during e.g. PEPTIDOGLYCAN biosynthesis; it can also inhibit other processes involving bactoprenol pyrophosphate (e.g. O-specific chain formation in LIPOPOLYSACCHARIDE biosynthesis) and can affect membrane permeability. Bacitracin is used clinically e.g. for the topical treatment of local infections, and as a FEED ADDITIVE for ruminants to decrease methane production in the RUMEN. back focal plane Of a convex lens: the focal plane furthest from the light source. back mutation (reverse mutation) (1) A MUTATION which reverses the effects of a FORWARD MUTATION by restoring the original nucleotide sequence. (2) Either a mutation as in sense 1 above, or an intragenic SUPPRESSOR MUTATION. background mutation Syn. SPONTANEOUS MUTATION. bacon spoilage See MEAT SPOILAGE. BACTEC culture systems Liquid media (marketed by Becton Dickinson) which can be used e.g. for the growth of Mycobacterium tuberculosis – growth being detectable more rapidly (∼1–2 weeks) than is usually possible on solid media (∼6 weeks). These media may be used for (i) detecting M. tuberculosis in clinical specimens, and (ii) examining an isolate of the pathogen for susceptibility to antibiotics; for the latter purpose an isolate is tested for growth (or lack of growth) in a medium containing a known amount of the given antibiotic. Earlier BACTEC systems were radiometric, i.e. they detected growth by detecting radioactive carbon dioxide produced from a radioactive substrate in the medium. A more recent system, the BACTEC MGIT 960 (MGIT = mycobacteria growth indicator tube), monitors growth by means of a fluorescent sensor system which detects the consumption of oxygen. [Evaluation of BACTEC MGIT 960: JCM (1999) 37 748–752.] bacteraemia (bacteremia) The condition in which viable bacteria are present in the bloodstream. (cf. PYAEMIA; SEPTICAEMIA.) bacteremia Syn. BACTERAEMIA. bacteria (singular: bacterium) (1) Formerly: a term which referred, collectively, to all prokaryotic microorganisms (see PROKARYOTE); the term was also used to refer to a population of specific prokaryote(s) of any given type. (2) All, or particular, members of the domain Bacteria (see next entry). Note. In literature prior to the 1980s ‘bacteria’ was always used with the meaning given in sense 1. With the establishment of the domain ARCHAEA (q.v.), appropriate usage is that given in sense 2. Bacteria A taxon (DOMAIN) comprising one of the two fundamentally distinct groups of prokaryotic microorganisms (see PROKARYOTE and ARCHAEA). (See also previous entry.) The bacteria are a diverse group of (usually) single-celled organisms. Most are free-living, occurring e.g. in soil, on plants, in various aquatic habitats, and even in antarctic snow [AEM (2000) 66 4514–4517]; some are important in the cycles of matter (see CARBON CYCLE, NITROGEN CYCLE, SULPHUR CYCLE). Bacteria are also found as symbionts in plants, animals and certain microorganisms (see CAEDIBACTER, MYCETOCYTE, ROOT NODULES, RUMEN). A minority of bacteria occur as intracellular or extracellular parasites or pathogens in man and/or other animals. In man, bacteria can cause a number of major and minor diseases – which include e.g. ANTHRAX, BOTULISM, BRUCELLOSIS, CHOLERA, DIPHTHERIA, DYSENTERY, ERYSIPELAS, GONORRHOEA, LEGIONNAIRE’S DISEASE, LEPROSY, LYME DISEASE, MENINGITIS, PLAGUE, PSEUDOMEMBRANOUS COLITIS, Q FEVER, SCARLET 70

Bacteria

Bacteria

Archaea

CYANOBACTERIA

GRAM POSITIVE

EURYARCHAEOTA

Anabaena sp

Bacillus subtilis Clostridium perfringens Corynebacterium xerosis Enterococcus faecalis Lactobacillus delbrueckii Listeria monocytogenes Mycobacterium tuberculosis Propionibacterium acnes Streptomyces coelicolor

Halobacterium halobium

Desulfurococcus mobilis

Methanobacterium bryantii Methanococcus jannaschii

Pyrodictium occultum

Gloeobacter sp Oscillatoria sp Prochloron didemni

Thermoplasma acidophilum

CRENARCHAEOTA

Sulfolobus solfatarius Thermoproteus tenax

PROTEOBACTERIA

(Alpha)

(Beta)

(Gamma)

(Epsilon)

Agrobacterium tumefasciens

Alcaligenes faecalis

Coxiella burnetii

Helicobacter pylori

Brucella abortus

Bordetella pertussis

Escherichia coli

Rickettsia spp

Neisseria gonorrhoeae Neisseria meningitidis

Haemophilus influenzae Legionella pneumophila

Spirillum natans

Proteus vulgaris Pseudomonas aeruginosa Vibrio parahaemolyticus

BACTERIA: examples of species in some of the groups in a current taxonomic scheme for the Bacteria (some species of the domain Archaea are also shown); the lines are not intended to reflect evolutionary distances between the organisms. A number of groups not shown in the figure are outlined in the text; note, for example, that the Gram-positive species are divided into ‘high GC%’ and ‘low GC%’. Reproduced from Bacteria, 5th edition, Figure 16.5, page 436, Paul Singleton (1999) copyright John Wiley & Sons Ltd (UK) (ISBN 0471-98880-4) with permission from the publisher. FEVER, SYPHILIS, TETANUS, TOXIC SHOCK SYNDROME, TRACHOMA,

bacterial morphology: Microbiology (1998) 144 2803–2808]. (See also e.g. COCCOBACILLUS, FILAMENT, L FORM, MYCELIUM, PLEOMORPHISM (sense 1), SPIROCHAETALES and VIBRIO (sense 2).) In general, the shape of a bacterium is determined primarily by its species. (cf. PROTOPLAST.) According to species, a bacterial cell may have certain appendages: see e.g. FIMBRIAE, FLAGELLUM, PILI, PROSTHECA AND SPINA. (See also CAPSULE.) Many types of bacteria are motile (see MOTILITY); motile species commonly exhibit CHEMOTAXIS. Cells may occur singly or in pairs, chains, clusters, PACKETS, PALISADES etc.; some bacteria of the order ACTINOMYCETALES form a mycelium. (See also COENOCYTE and CONSORTIUM.) Some species form EXOSPORES; some form ENDOSPORES. Members of the MYXOBACTERALES form fruiting bodies. A bacterial cell lacks the sophisticated physical compartmentalization of eukaryotic cells. However, bacteria exhibit a ‘functional compartmentalization’ [FEMS Reviews (1993) 104 327–346]; this refers to various molecular strategies – such as the self-assembly of protein components of composite enzyme systems (see e.g. PROTEASOME). Moreover, the localization of proteins in a bacterium now appears to be much more organized than was previously supposed [Science (1997) 276 712–718]. [Dynamic spatial regulation in the bacterial cell: Cell (2000) 100 89–98.]

TUBERCULOSIS, TULARAEMIA, TYPHOID, TYPHUS FEVERS, WHIPPLE’S

and WHOOPING COUGH. Bacteria cause economically important diseases in livestock as well as infections in wild animals – see e.g. CATTLE DISEASES, FISH DISEASES, HORSE DISEASES, PIG DISEASES, SHEEP DISEASES. (See also INSECT DISEASES.) Relatively few bacteria cause disease in plants (but see e.g. ERWINIA, SPIROPLASMA, XANTHOMONAS). Predatory/bacteriolytic bacteria include species of ANAEROPLASMA, BDELLOVIBRIO, MYXOBACTERALES and VAMPIROVIBRIO. Bacteria are used in a number of commercial/manufacturing processes: see e.g. BIOPOL, DAIRY PRODUCTS, GLUTAMIC ACID, LEACHING, PICKLING, RETTING, SAUERKRAUT, SOY SAUCE, SUBTILISINS, VINEGAR, VITAMIN B12. Certain antibiotics (e.g. POLYMYXINS, STREPTOMYCIN and some b-LACTAM ANTIBIOTICS) can be synthesized by bacteria. (See also BIOASSAY, BIOFUEL CELL and BIOLOGICAL CONTROL.) In size, most bacteria are between 1 and 10 µm (maximum dimension). The smallest range from 600 µm) is Epulopiscium fishelsoni [Nature (1993) 362 239–241]. The basic shapes of bacteria are BACILLUS (sense 2) (also called ‘rod’), COCCUS and SPIRILLUM (sense 1); the coccus seems likely to be a degenerate form of the rod [evolution of DISEASE

71

bacterial blotch of mushrooms In most species there is a characteristic type of CELL WALL in which PEPTIDOGLYCAN is a common constituent (cf. ARCHAEA); the mycoplasmas are atypical in being wall-less. Ester-linked lipids occur in the bacterial CYTOPLASMIC MEMBRANE (cf. ARCHAEA). In common with e.g. higher animals and plants, the cytoplasmic membrane in many (not all) bacteria (and in some archaeans) contains aquaporins and/or glycerol facilitators: see MIP CHANNELS. (See also OSMOREGULATION.) Various TRANSPORT SYSTEMS are associated with the cell envelope (see e.g. PROTEIN SECRETION and PTS). TWO-COMPONENT REGULATORY SYSTEMS regulate responses to various environmental stimuli. Energy may be obtained by FERMENTATION (sense 1), by RESPIRATION, and/or (in e.g. CYANOBACTERIA) by PHOTOSYNTHESIS. (See also PURPLE MEMBRANE.) According to species, bacteria may be obligate or facultative AEROBES or ANAEROBES. They may be CHEMOTROPHS and/or PHOTOTROPHS, HETEROTROPHS or AUTOTROPHS, and some are CHEMOLITHOAUTOTROPHS. The bacterial genome commonly consists of covalentlyclosed circular DNA; however, in some bacteria (e.g. Borrelia burgdorferi and species of Streptomyces) the DNA is linear. The number of chromosomes per cell depends e.g. on species and on the growth rate. In Vibrio cholerae the genome consists of two circular chromosomes (chromosome 1 = ca. 2961 kb; chromosome 2 = ca. 1073 kb) [Nature (2000) 406 477–483]. For some species, the complete sequence of nucleotides in the genome has been determined – e.g. Borrelia burgdorferi [Nature (1997) 390 580–586], Buchnera [Nature (2000) 407 81–86], Escherichia coli [Science (1997) 277 1453–1474], E. coli O157:H7 [Nature (2001) 409 529–533; erratum: Nature (2001) 410 240], Helicobacter pylori [Nature (1997) 388 539–547], Mycobacterium tuberculosis [Nature (1998) 393 537–544] and Neisseria meningitidis (serogroup A strain) [Nature (2000) 404 502–506]. In many bacteria the genome is supplemented by one or more plasmids (see PLASMID); bacterial plasmids are commonly circular, but some are linear. Certain bacteria are normally plasmidfree; they include species of Anaplasma, Bartonella, Brucella and Rickettsia. (See also BACTERIOPHAGE and LYSOGENY.) Reproduction occurs asexually, usually by BINARY FISSION but sometimes by BUDDING or TERNARY FISSION. (See also CELL CYCLE.) A developmental cycle occurs e.g. in CAULOBACTER, CHLAMYDIA and RHODOMICROBIUM. Despite the lack of sexual reproduction, gene transfer between bacteria can occur by CONJUGATION, CONJUGATIVE TRANSPOSITION, TRANSDUCTION or TRANSFORMATION. Taxonomy. Until the 1980s, bacterial TAXONOMY was based primarily on criteria such as staining reaction, morphology and substrate requirements. Although some of the earlier taxa (e.g. ENTEROBACTERIACEAE) are still recognized, the modern approach is based mainly on molecular criteria, i.e. base sequences in nucleic acids. Using molecular criteria, bacteria have been divided into a number of groups which are believed to reflect evolutionary affinities; some of these groups are shown in the figure on page 71. An outline of the scheme is as follows.

• Gram-positive bacteria (high GC%). Species of Arthrobacter, Bifidobacterium, Corynebacterium, Faenia, Frankia, Gardnerella, Mycobacterium and Streptomyces. • Gram-positive bacteria (low GC%). Species of e.g. Bacillus, Clostridium, Desulfotomaculum, Enterococcus, Erysipelothrix, Gemella, Lactobacillus, Leuconostoc, Listeria and Pediococcus. • Green non-sulphur bacteria. Species of e.g. Chloroflexus. • Planctomyces/Chlamydia group. Species of e.g. Chlamydia, Isosphaera, Planctomyces. • Proteobacteria (purple bacteria). See PROTEOBACTERIA. • Spirochaetes. Species of e.g. Borrelia, Leptonema, Spirochaeta, Treponema. • Thermotogales. Species of e.g. Fervidobacterium, Geotoga, Thermotoga. Bacteria from ancient sources. It has been reported that an organism resembling Bacillus has been cultured from a brine inclusion located within a salt crystal believed to be ∼250 million years old [Nature (2000) 407 897–900; discussion 844–845]. [Bacteria (general text): Book ref. 223.] bacterial blotch of mushrooms See BROWN BLOTCH and GINGER BLOTCH. bacterial endocarditis ENDOCARDITIS caused by bacteria. bacterial fin rot A common FISH DISEASE in which infection e.g. by species of Flexibacter, Aeromonas or Pseudomonas leads to progressive necrosis of fins and tail; stress is an important factor in disease development. Secondary SAPROLEGNIASIS is common. bacterial gill disease A FISH DISEASE affecting salmonids. Filamentous bacteria (genus uncertain) cover the gills, and death by asphyxia may result. The primary cause is unknown, but overcrowding is a predisposing factor. bacterial kidney disease See KIDNEY DISEASE. bacterial leaching (of ores) See LEACHING. bacterial overgrowth syndrome See GASTROINTESTINAL TRACT FLORA. bacterial vaginosis (non-specific vaginitis) A syndrome characterized by a malodorous vaginal discharge and an increase, in the vagina, in the numbers of certain bacteria – e.g. species of Bacteroides and GARDNERELLA (see also MOBILUNCUS); under these conditions the vaginal pH is usually >4.5, the Eh of the vaginal epithelial surface is ca. +71 mV to −257 mV (normal values ca. +322 mV to +137 mV) [JID (1985) 152 379–382], and ‘clue cells’ (vaginal epithelial cells coated with small Gramnegative rods) can usually be seen in vaginal smears. In cases of bacterial vaginosis, vaginal secretions typically give a fishy, amine-like odour when treated with 10% KOH. [Diagnostic criteria: Am. J. Med. (1983) 74 14–22; JCM (1985) 22 686–687.] Bacteriastrum See DIATOMS. bactericidal (bacteriocidal) Able to kill at least some types of bacteria. (cf. BACTERIOSTATIC.) bactericidal/permeability-increasing protein See BPI PROTEIN. bactericidin (1) An antibody which, under appropriate conditions, can act as a bactericidal agent. (2) A non-specific bactericidal plasma factor (see e.g. COMPLEMENT FIXATION). (3) An antibacterial protein produced by an invertebrate – see e.g. SARCOTOXINS. bacterin A VACCINE containing killed bacterial cells. bacteriochlorophylls See CHLOROPHYLLS. bacteriocidal Syn. BACTERICIDAL. bacteriocin (bacteriocine) Any of a wide variety of (usually) protein or peptide ANTIBIOTICS, produced by certain strains of

• Cyanobacteria (see CYANOBACTERIA). • Cytophaga/Flexibacter/Bacteroides group. As well as the named organisms, the group includes species of e.g. Flavobacterium, Microscilla, Saprospira, Sphingobacterium, Spirosoma and Sporocytophaga. • Fibrobacteria. Fibrobacter spp. • Fusobacteria. Fusobacterium, Leptotrichia spp. 72

bacteriocin Gram-positive and Gram-negative bacteria, which are bacteriostatic or bactericidal – often specifically to organisms that are closely related to the bacteriocin-producing strain. Bacteriocins include e.g. COLICINS, MICROCINS and LANTIBIOTICS. Agents analogous to bacteriocins are produced by members of the Archaea; these agents (e.g. the halocins produced by halobacteria) are apparently not homologous to any bacteriocin in terms of amino acid sequences. In size and structure, bacteriocins range from a simple modified amino acid (microcin A15), through short peptides and high-MWt colicins, to phage-like PYOCINS. (See also BACTERIOPHAGE fBA1.) Some bacteriocins (lantibiotics) undergo distinctive post-translational modification which is necessary for their activity. The lantibiotic LACTICIN 3147 (produced by Lactobacillus lactis subsp lactis) is a two-component bacteriocin – both peptides being necessary for activity; moreover, each of the two peptides needs modification by a separate enzyme [Microbiology (2000) 146 2147–2154]. Evolutionary relationships are evident within some groups of bacteriocins. [Molecular mechanisms of bacteriocin evolution: ARG (1998) 32 255–278.] Bacteriocins are commonly encoded by PLASMIDS (see e.g. COLICIN PLASMID); bacteriocin-encoding plasmids include both conjugative and non-conjugative types. Examples of chromosomally encoded bacteriocins include ‘bacteriocin 28b’ (a colicin encoded by Serratia marcescens) and some of the class IIa bacteriocins produced by lactic acid bacteria (see later). The mode of regulation of bacteriocin synthesis varies among the different groups. For example, synthesis of colicins is promoted by those conditions which trigger the SOS SYSTEM (see COLICIN PLASMID). By contrast, many bacteriocins of the lactic acid bacteria appear to be regulated by a three-component system which includes a histidine protein kinase, a response regulator, and an induction factor. (cf. TWO-COMPONENT REGULATORY SYSTEM). Induction factors (IFs) are small heat-stable peptides produced by the bacteriocinogenic cell. The mechanism by which IFs promote synthesis of bacteriocin is unknown, but it has been suggested that they may trigger synthesis as a result of their gradual intracellular accumulation or that their influence may reflect environmental factors. Synthesis of the bacteriocin sakacin A (produced by Lactobacillus sake) is reported to be regulated by a three-component system (which includes a 23-amino-acid cationic peptide) in a temperature-sensitive way [Microbiology (2000) 146 2155–2160]. The bacteriocin divercin V41, produced by Carnobacterium divergens strain V41, may be regulated by a two-component system [Microbiology (1998) 144 2837–2844]. The different types of bacteriocin are released in different ways from the cells which synthesize them. For example, release of colicins depends on a lysis protein which causes a (non-specific) increase in the permeability of the cell envelope – allowing dispersal of the bacteriocin (but with concomitant adverse effects on the producing cell). By contrast, certain bacteriocins (e.g. ENTEROCIN P) are secreted via a sec-dependent pathway, while some class IIa bacteriocins of the lactic acid bacteria are reported to be secreted by ABC TRANSPORTERS. The import of some types of bacteriocin (e.g. colicins) into sensitive cells depends on the binding of the bacteriocin to a specific cell-surface receptor. In most or all cases, uptake of colicins appears to be an energy-dependent process (pmf being needed for transport across the outer membrane, and ATP hydrolysis being involved in transport across the cytoplasmic membrane); the route of translocation through the cell envelope depends on the given colicin (see groups A and B COLICINS). By contrast,

studies on pediocin PA-1 (a class IIa bacteriocin produced by Pediococcus spp) reported binding to lipsomes in the absence of a protein receptor [AEM (1997) 63 524–531] – suggesting that a protein receptor may not be an absolute requirement for these bacteriocins; it may be that these (cationic) bacteriocins bind to anionic phospholipid groups in the membrane. A given bacteriocin acts on a susceptible target cell in a characteristic way. Some bacteriocins (e.g. some colicins, lantibiotics) form pores in the cytoplasmic membrane; some (e.g. microcin B17) inhibit DNA gyrase; some (e.g. LYSOSTAPHIN) disrupt PEPTIDOGLYCAN; and some (e.g. CLOACIN DF13) cleave 16S rRNA. It appears that, in some cases, a single bacteriocin molecule can be lethal for a sensitive cell. (Although bacteriocins are active primarily against bacteria, certain colicins and VIBRIOCINS have been reported to affect some types of eukaryotic cell [JAC (1980) 6 424–427].) Various mechanisms provide a cell with immunity to the bacteriocin(s) it encodes. For example, while cells actively secreting colicins are damaged by their lysis proteins, neighbouring cells of the same strain, repressed for colicin synthesis, are protected by immunity proteins (see COLICINS). Cells producing LYSOSTAPHIN achieve immunity by modifying their own peptidoglycan. Cells producing the lantibiotic EPIDERMIN achieve immunity by operating an ATP-dependent pump (transport system) which actively secretes any molecules of the agent that are taken up. Biotechnological applications of bacteriocins. The great diversity of bacteriocins, and the ability of many of them to kill/inhibit certain pathogenic bacteria, has prompted much research into the possibility of using particular bacteriocins as antibiotics and/or as food preservatives/additives (see e.g. LACTICIN 3147). Particularly useful bacteriocins are produced by certain LACTIC ACID BACTERIA (e.g. species of Carnobacterium, Enterococcus, Lactobacillus and Lactococcus), some of which are highly active against important food-borne pathogens (such as Listeria monocytogenes). According to structural and other characteristics, bacteriocins of the lactic acid bacteria have been classified into four classes [FEMS Reviews (1993) 12 39–86]: Class I. LANTIBIOTICS: small, typically pore-forming peptides containing unusual constituents (such as lanthionine) – e.g. EPIDERMIN and NISIN. Class II. Small peptides (30 kDa) heat-labile proteins; they include helveticin J, lactacin A and lactacin B. Class IV. Bacteriocins which consist of a protein moiety plus at least one non-protein (e.g. lipid) constituent which is necessary for activity. They include lactocin 27, leuconocin S and plantaricin S. Other bacteriocins. See also PESTICIN I, PYOCINS, STAPHYLOCOCCIN and ULCERACIN 378. Bacteriocins are also produced by Bacillus megaterium (megacins), Klebsiella spp (klebicins), Listeria monocytogenes (monocins [Zbl. Bakt. Hyg. A (1986) 261 73

bacteriocin 28b bacteriocyte In certain invertebrates, particularly insects: a specialized cell which contains intracellular bacterial symbionts. (cf. MYCETOCYTE.) Bacteriocytes occur e.g. in the cockroach (see BLATTABACTERIUM), in some marine sponges (containing ‘Aphanocapsa’ endosymbionts) and in aphids (see BUCHNERA). bacteriolysis The lysis (rupture) of bacterial cells. In nature, various microorganisms produce enzymes or antibiotics which lyse bacteria – either to provide nutrients or (presumably) for competitive advantage. (See e.g. ANAEROPLASMA, ENSIFER, LYSOSTAPHIN, MUSHROOM CULTIVATION, MYXOBACTERALES.) Most BACTERIOPHAGES eventually lyse their host cells to release their progeny. In the laboratory bacteria may be lysed mechanically or enzymically (see CELL DISRUPTION). bacterio-opsin See OPSIN. bacteriophaeophytin A PHAEOPHYTIN derivative of a bacteriochlorophyll. Bacteriophaeophytins occur e.g. in the REACTION CENTRES in a number of ‘purple’ photosynthetic bacteria and in the cytoplasmic membrane of some ‘green’ photosynthetic bacteria. bacteriophage (phage) Any VIRUS whose host is a bacterium. (Viruses which infect cyanobacteria are conventionally called CYANOPHAGES.) Most – probably all – bacteria can be infected by particular phages; commonly, a given phage can infect only one or a few strains or species of bacteria. The consequences of phage infection depend on phage and host, and to some extent on

12–28]) and by Clostridium botulinum (boticins), C. butyricum (butyricins) and C. perfringens (perfringocins). (cf. AGROCINS and KILLER FACTOR.) bacteriocin 28b See COLICINS. bacteriocin typing A form of TYPING in which strains of bacteria are distinguished on the basis of the BACTERIOCIN(s) they produce or the bacteriocin(s) to which they are susceptible. In one common form of bacteriocin typing (used e.g. for colicins and pyocins) the strain under test is inoculated in a diametrical strip on a blood agar plate which is incubated for ca. 12–24 hours; growth is scraped from the plate and discarded, and any cells remaining on the plate are killed by exposure to chloroform. The chloroform is allowed to evaporate, leaving a band of bacteriocin-impregnated agar. Indicator strains are then inoculated onto the agar in lines perpendicular to, and passing through, the bacteriocin-containing band; on incubation, the growth of sensitive strains is inhibited inside the band. In this procedure the test organism is typed by the range of strains susceptible to its bacteriocin(s). [Revised method for pyocin typing: JCM (1984) 20 47–50.] bacteriocinogenic Able to produce a BACTERIOCIN. bacteriocinogenic factor The earlier name for any PLASMID that encodes a BACTERIOCIN. bacteriocuprein A bacterial CuZnSOD (see SUPEROXIDE DISMUTASE).

BACTERIOPHAGES: some representative examplesa Bacteriophage (or phage group)

Virion morphology

Principal host(s)

isometric head + long non-contractile tail isometric head + long contractile tail isometric head + short tail isometric head + short non-contractile tail isometric head + long contractile tail isometric head + long contractile tail isometric head + minimal tail elongated head + short non-contractile tail isometric head + long contractile tail elongated head + long contractile tail isometric head + short non-contractile tail isometric with internal lipid membrane (no tail)

Escherichia coli enterobacteria Acholeplasma laidlawii Escherichia coli Escherichia coli Escherichia coli Salmonella Bacillus subtilis Bacillus subtilis Escherichia coli enterobacteria various

pleomorphic; envelope enclosing a DNA–protein complex icosahedral with internal lipid membrane

Acholeplasma laidlawii

Genome: ccc ssDNAb Inoviridae (e.g. f1, MV-L51) Microviridae (e.g. fX174)

filamentous or rod-shaped icosahedral

various enterobacteria

Genome: dsRNAb f6

enveloped nucleocapsid

Pseudomonas syringae pv. phaseolicola

icosahedral

various

dsDNAb

Genome: linear l Mu MV-L3 N4 P1 P2 P22 f29 SPO1 T4 T7 Tectiviridae (e.g. PRD1, AP50) Genome: ccc dsDNAb MV-L2 PM2

Alteromonas espejiana

ssRNAb

Genome: Leviviridae (e.g. MS2, Qb) a b

See separate entries for details. In the virion.

ccc = covalently closed circular; ds = double-stranded; ss = single-stranded. 74

bacteriophage conversion have indicated that, on attaching to the host cell, the phage ejects proteins that may assemble to form a channel across the bacterial cell envelope through which the genome is translocated; it has been speculated that two of the ejected proteins may form the components of a ‘motor’ that rachets phage DNA into the host cell [Mol. Microbiol. (2001) 40 1–8]. For phage development to proceed, the phage nucleic acid must escape degradation by the host’s RESTRICTION ENDONUCLEASE system. For a general account of viral replication strategies see VIRUS; for detailed accounts of particular phages see following entries. Virion assembly may occur by the spontaneous aggregation of the various phage components, but the more complex virions require the participation of non-structural phagecoded proteins (see SCAFFOLDING PROTEIN). Host cell lysis may be induced by phage-coded enzymes or by activation of host cell autolysins. (See also LYSIS FROM WITHOUT, LYSIS PROTEIN and ONE-STEP GROWTH EXPERIMENT.) Bacteriophages can cause considerable economic problems in certain biotechnological processes such as the manufacture of dairy products, antibiotics, etc. A few phages are medically important in that they encode certain toxins (see BACTERIOPHAGE CONVERSION). In microbiology, phages are useful e.g. for PHAGE TYPING, for achieving gene transfer between bacteria (see TRANSDUCTION), for probing the molecular biology of bacteria, etc. Phages may be cultivated and/or assayed e.g. by inoculation at low multiplicity of infection on a LAWN PLATE of susceptible bacteria (see PLAQUE and PLAQUE ASSAY). They may also be cultivated in broth cultures of host bacteria, the activity of virulent phages being indicated by the progressive decrease in turbidity of the culture as the cells lyse; a suspension of phages may be prepared from the lysate e.g. by CENTRIFUGATION or by membrane FILTRATION to remove bacterial debris. bacteriophage 7-7-1 See FLAGELLOTROPIC PHAGE. bacteriophage 21 See LAMBDOID PHAGES. bacteriophage 82 See LAMBDOID PHAGES. bacteriophage 434 See LAMBDOID PHAGES. bacteriophage 1307 See PLASMAVIRIDAE. bacteriophage a3 See MICROVIRIDAE and BACTERIOPHAGE G4. (Also: a dsDNA-containing phage of ‘Achromobacter sp 2’ [JGV (1981) 53 275–281].) bacteriophage a15 See LEVIVIRIDAE. bacteriophage AP50 See TECTIVIRIDAE. bacteriophage Bam35 See TECTIVIRIDAE. bacteriophage b See LEVIVIRIDAE. (cf. Corynephage b – see DIPHTHERIA TOXIN.) bacteriophage BF23 A bacteriophage which infects Escherichia coli and which resembles phage T5. (See also BTUB PROTEIN.) bacteriophage BPB1 See STYLOVIRIDAE. bacteriophage Cf See INOVIRUS. bacteriophage c See STYLOVIRIDAE. bacteriophage conversion (phage conversion) In a bacterium: the acquisition, loss or modification of one or more phenotypic characteristics as a result of infection by a BACTERIOPHAGE – typically a temperate phage (lysogenic conversion); it may result e.g. from the expression of phage genes or from inactivation of one or more bacterial genes due to insertion of a prophage into the bacterial chromosome. (Phenotypic alteration in a recipient cell due to TRANSDUCTION of bacterial DNA is not regarded as phage conversion.) Phage conversion is responsible for toxigenicity in a number of pathogenic bacteria. For example, phages encode CHOLERA TOXIN, DIPHTHERIA TOXIN and the shiga-like toxins of enterohaemorrhagic strains of Escherichia coli (including O157:H7)

conditions. Some (virulent ) phages always induce a LYTIC CYCLE in the host cell, while other (temperate) phages can establish a stable, non-lytic relationship (LYSOGENY) with the host. Some phages can replicate and produce progeny virions within the host cell without killing or lysing it (see INOVIRIDAE and INOVIRUS). Phages of the MV-L3 PHAGE GROUP apparently kill their host cells without actually lysing them. The antibacterial activity of phages has been exploited (primarily in Eastern Europe and the former Soviet Union) for both therapeutic and prophylactic use against various bacterial pathogens (including strains of Escherichia, Klebsiella, Proteus, Pseudomonas, Salmonella, Shigella, Staphylococcus and Streptococcus) [AAC (2001) 45 649–659]. Bacteriophages are a highly diverse group of viruses. Of the many hundreds known, relatively few have been thoroughly characterized [guidelines for phage characterization: AVR (1978) 23 1–24]. Some phages have been included in the overall taxonomic scheme for the viruses [Book ref. 23], and these are classified in the families CORTICOVIRIDAE, CYSTOVIRIDAE, INOVIRIDAE, LEVIVIRIDAE, MICROVIRIDAE, MYOVIRIDAE, PLASMAVIRIDAE, PODOVIRIDAE, STYLOVIRIDAE and TECTIVIRIDAE; however, many phages remain unclassified. Morphologically, phage virions may be small and icosahedral, ca. 23–32 nm diam. (e.g. Qb and fX174); filamentous, ca. 760–1950 × 6 nm (INOVIRUS); pleomorphic (e.g. BACTERIOPHAGE MV-L2); or – in many phages – complex in structure with a polyhedral ‘head’ (the CAPSID) linked (often via a more or less complex connecting structure) to a long or short, simple or complex, contractile or non-contractile ‘tail’ (see e.g. PODOVIRIDAE, STYLOVIRIDAE, T-EVEN PHAGES). While in many phages the virions consist only of protein and the nucleic acid genome, some have a significant content of lipid – either as an external ENVELOPE (e.g. in f6 and MV-L2) or as an internal layer (in BACTERIOPHAGE PM2 and phages of the TECTIVIRIDAE); the T-even phages contain e.g. dihydropteroyl hexaglutamate, phages of the MV-L3 group contain fucose, and MS2 contains spermidine. The genome of a phage may be linear dsDNA, ccc dsDNA, ccc ssDNA, linear dsRNA or linear ssRNA (see Table). In some of the DNA phages the DNA contains unusual bases: e.g. PBS1 contains deoxyuracil instead of thymine, fW-14 contains a-putrescinylthymine, T-even phages contain hydroxymethylcytosine instead of cytosine, SP8 and SPO1 contain 5hydroxymethyluracil instead of thymine. (See also BACTERIOPHAGE MU and RESTRICTION–MODIFICATION SYSTEM.) The phage replication cycle begins when the virion adsorbs to the host at specific cell-surface sites: e.g., particular components of the cell wall (see e.g. BTUB PROTEIN and LAMB PROTEIN), the flagellum (see FLAGELLOTROPIC PHAGE), a sex pilus (see ANDROPHAGES), etc. Some phages adsorb only in the presence of appropriate concentrations of certain ions or of certain organic ‘adsorption cofactors’ (e.g. tryptophan for BACTERIOPHAGE T4). In Gram-negative bacteria penetration is believed to occur – at least in some phages – at ADHESION SITES. Either the entire virion, or the phage genome with or without certain phage proteins, enters the host cell: see e.g. INOVIRUS, LEVIVIRIDAE, and entries for bacteriophages N4, f6 and T4 for examples. For at least some of the phages with contractile tails (see MYOVIRIDAE) – e.g. BACTERIOPHAGE T4 (q.v.) – the genome is understood to be injected (by a syringe-like action) into the periplasmic region of the bacterium. However, many phages have non-contractile tails, and some are entirely tail-less; hitherto, little information has been available on the way in which the genome of such phages is translocated into the host cell. Studies on phage T7 75

bacteriophage CTX8 bacteriophage fr See LEVIVIRIDAE. bacteriophage G4 An isometric SSDNA PHAGE of the MICROVIRIDAE. On penetrating the host cell, the ss cccDNA genome is coated with host SSB protein; a GC-rich region between genes F and G probably remains uncoated. Stage I (see SSDNA PHAGE) is independent of host dnaB function (as it is in microviruses St-1, a3, fK and fXtB – cf. BACTERIOPHAGE fX174). The F –G intergenic region seems to fold into a secondary structure [JV (1986) 58 450–458] which is capable of direct (dnaB-independent) recognition by host PRIMASE (cf. PRIMOSOME and DNAB GENE). Primase synthesizes a short RNA primer at a unique site (ori ) in the intergenic region. The c strand is completed as in other SSDNA PHAGES. Stage II in G4 requires dnaB function, presumably for initiation of n strand synthesis. (Phages St-1, fK and a3 do not require dnaB at any stage.) G4 n strand synthesis begins at the n strand origin (Ov ) in gene A; the c strand origin (Oc ) in the F –G intergenic region is on the opposite side of the molecule. n strand synthesis seems to proceed by the displacement of the old n strand as a closed loop (D LOOP) at the Ov site, and hence is independent of a gpA-induced nick (cf. BACTERIOPHAGE fX174). Synthesis of n strand by DNA polymerase III holoenzyme and Rep protein proceeds unidirectionally. When the replication fork passes Oc , primer synthesis can begin on the displaced loop, and c strand synthesis can proceed in the opposite direction. The parental n and c circles may separate before replication of either is complete. G4 seems to resemble fX174 (q.v.) in stage III and morphogenesis. bacteriophage G6 See MICROVIRIDAE and BACTERIOPHAGE fX174. bacteriophage G13 See MICROVIRIDAE and BACTERIOPHAGE fX174. bacteriophage G14 See MICROVIRIDAE and BACTERIOPHAGE fX174. bacteriophage HM3 See MYOVIRIDAE. bacteriophage I3 See MYCOBACTERIOPHAGES. bacteriophage If1 An INOVIRUS which adsorbs specifically to I-type pili of enterobacterial hosts; phage If2 is very similar. bacteriophage If2 See BACTERIOPHAGE IF1. bacteriophage IKe An INOVIRUS specific for enterobacteria which contain an IncN plasmid; the phage can apparently establish a pseudolysogenic infection of its host [CJM (1978) 24 1595–1601]. [Nucleotide sequence and genetic organization of IKe genome: JMB (1985) 181 27–39.] bacteriophage L1 group See PLECTROVIRUS. bacteriophage L2 group See PLASMAVIRIDAE. bacteriophage L3 group See MV-L3 PHAGE GROUP. bacteriophage L4 A BACTERIOPHAGE closely related to BACTERIOPHAGE P22 but defective in maintenance of lysogeny; it is commonly used as a transduction vector in Salmonella typhimurium. bacteriophage L17 See TECTIVIRIDAE. bacteriophage L34a See BACTERIOPHAGE CONVERSION. bacteriophage l A temperate BACTERIOPHAGE (family STYLOVIRIDAE) which infects Escherichia coli. Head: icosahedral, ca. 55 nm diam., composed of two major structural proteins (gpE and gpD) and several minor proteins (gpB, gpC, gpFII ). Tail: long (ca. 150 × 10 nm), flexible, tubular, non-contractile, joined to the head via a ‘neck’ or ‘connector’ region, and terminating at the distal end in a small basal structure to which is attached a single fibre (the adsorption organelle). (See also LAMB PROTEIN.) Genome: linear dsDNA (48514 bp long [nucleotide sequence: JMB (1982) 162 729–773]) with single-stranded 12-base 5′ STICKY ENDS (designated cos). On infection of a host cell, phage DNA is transferred to the host through the tail and is immediately circularized by base-pairing between the sticky ends followed by host DNA ligase action. Subsequent events may eventually lead either to host cell lysis (involving the production and release of

(see SHIGA TOXIN). The enterotoxin A of Staphylococcus aureus (see ENTEROTOXIN) is phage-encoded in at least some strains. (See also BETACIN.) In Staphylococcus aureus, lipase activity is lost on infection with phage L54a owing to inactivation of the lipase structural gene (into which the prophage inserts) [JB (1986) 166 385–391]. Lysogenic conversion can also be manifested by a change in cell-surface antigens, i.e. a change in serotype. For example, in group E salmonellae, phage e15 converts antigens 3,10 to 3,15, and the LPS of the latter serotype can act as a receptor for phage e34 which, in turn, converts the antigen type to 3,15,34 (for the meaning of underlined numbers see KAUFFMANN–WHITE CLASSIFICATION). Phage-mediated modification of serotype is important e.g. when developing vaccine strains of a pathogen [see e.g. TIM (2000) 8 17–23]. (See also PSEUDOLYSOGENY.) bacteriophage CTX8 A temperate, filamentous ssDNA BACTERIOPHAGE which infects Vibrio cholerae and encodes CHOLERA TOXIN (as well as the Ace and Zot toxins). The double-stranded form of the genome can integrate into the bacterial chromosome in a site-specific, RecA-independent process. Isolates of lysogenic E1 Tor and O139 strains of V. cholerae typically contain tandem arrays of prophage DNA at a single locus within the large chromosome, and it appears that the presence of multiple copies of the prophage is necessary for the production of virions; it also seems that the genomes of progeny virions are formed by a process in which replicative forms of the phage develop through hybridization between adjacent prophages (or between a prophage and a (phage-related) RS1 element in the chromosome) [PNAS (2000) 97 8572–8577]. The cell-surface receptor for CTX8 occurs on so-called toxin coregulated pili (TCP) (encoded by a chromosomal PATHOGENICITY ISLAND); genes encoding TCP and the cholera toxin are jointly, and positively, regulated by transcriptional regulator proteins (ToxR, ToxS, ToxT) which apparently become active on receipt of appropriate signals within the gut. Lysogenic conversion of (non-lysogenic) cells of V. cholerae can occur in the mammalian gut in the presence of phage-donating strains; this apparently reflects infection by phage following induction of TCP receptors by the gut-derived signals. [Science (1996) 272 1910–1914; Cell (1996) 87 795–798; Mol. Microbiol. (1997) 24 917–926; TIM (1998) 6 295–297.] Infection of V. cholerae by CTX8 is dependent on the tolQRA gene products [JB (2000) 182 1739–1747]. In the classical biotype of V. cholerae, the prophages are present either singly or as two fused prophages, and integration occurs at two sites; this biotype produces cholera toxin but, apparently owing to deficiencies in the structure of arrays (and the absence of RS1), does not produce virions [JB (2000) 182 6992–6998]. bacteriophage D108 A mutator bacteriophage which is very similar to BACTERIOPHAGE MU; the phage D108 genome shows ca. 90% homology with that of phage Mu, differing mainly in the early-gene region at the left end [EMBO (1985) 4 3031–3037]. bacteriophages e15 , e34 See BACTERIOPHAGE CONVERSION. bacteriophage f1 See INOVIRUS. bacteriophage f2 See LEVIVIRIDAE. bacteriophage F116 A temperate, transducing phage (family STYLOVIRIDAE) which infects Pseudomonas aeruginosa; in lysogenic cells the prophage appears to have an extrachromosomal location [JV (1977) 22 844–847]. bacteriophage fd See INOVIRUS. 76

bacteriophage l head and tail genes and morphogenesis cos A

J

b

att

recombination int xis red

DNA replication

regulation gam cIII

pI

N pL

cI

cro pR

cII pRE

O

P

lysis Q

ori

S

R cos

pR′

pRM

Nu3 Nu1AWB C D E F I F II Z U V G T HM L K I J cIII

N

nutL cI oL pL

pRM cro nutR cII oR PRE pR

BACTERIOPHAGE l. Simplified map of the virion genome (not drawn to scale). See entry for explanation.

progeny phages) or to LYSOGENY (during which l DNA becomes integrated into the host chromosome); the initial sequence of events is common to both pathways. Lytic cycle. Transcription of l DNA by the host RNA polymerase proceeds leftwards from promoter pL and rightwards from promoter pR , stopping at rho-dependent terminators shortly beyond genes N and cro (‘immediate early’ genes), respectively (see figure). gpN functions as an antiterminator which is specific for transcription initiated at the early promoters pL and pR ; gpN recognizes special sites (nutL and nutR) – regions of hyphenated dyad symmetry – downstream from pL and pR , and when the host RNA polymerase traverses these sites it is modified by gpN (in the presence of the host nusA gene product) such that it can read through subsequent terminators. As a result, genes to the left of N (cIII . . . att) and to the right of cro (cII . . . Q) – delayed early genes – are expressed. Expression of cro is necessary for the continuation of the lytic cycle (see later). gpN is unstable (half-life ca. 5 min), so that continued N expression is necessary for ongoing transcription of the delayed early genes. l DNA REPLICATION is initiated at a site (ori ) in the O gene and requires gpO, gpP , and certain host proteins, including DnaB protein, primase (DnaG protein), RNA polymerase, and components of the DNA polymerase III holoenzyme (but not e.g. dnaA, dnaC or dnaI functions). l gpO binds both to a 19-bp tandem repeat in the ori region and to l gpP ; gpP interacts with DnaB protein and appears to act as an analogue of E. coli DnaC protein (see PRIMOSOME). Initially, the l cccDNA is replicated by the CAIRNS MECHANISM, but later replication proceeds by a ROLLING CIRCLE MECHANISM to yield doublestranded concatemers. Phage structural components (and e.g. lysozyme necessary for host cell lysis) are encoded by late phage genes (S, R, A . . . J – juxtaposed by circularization of the genome); transcription of these genes is turned on by the delayed early gene product gpQ, which functions as an antiterminator of late mRNA initiated at pR′ . Phage morphogenesis is complex, involving host proteins as well as many phage-coded functions. In essence, gpB and gpC appear to form a complex with gpNu3, and gpE is then incorporated; these components undergo modification (fusion/cleavage reactions), and the scaffolding protein gpNu3 is cleaved during or after its elimination from the head precursor. Concatemeric l DNA is cut (by a gpNu1–gpA complex) at a cos site; a left cos site is inserted into the capsid precursor, and DNA insertion continues until the next cos site is reached, when the DNA is cleaved. (cf. COSMID.) The resulting head structure is stabilized by the addition of gpD, gpW and gpFII. The tail is assembled separately and

interacts spontaneously with the completed head to form the mature infectious virion. Lysogeny and the lysis/lysogeny decision. During the early period of phage transcription, the system is committed neither to lysis nor to lysogeny, expression of immediate early and delayed early genes being necessary for both pathways. Expression of late genes results in lysis, while establishment of lysogeny requires the repression of most of the l genes by a repressor protein (gpcI ); gpcI prevents both leftward and rightward transcription by binding to operator regions (oL and oR ) that overlap pL and pR , respectively. When a host cell is first infected, cI cannot be expressed. However, transcription of N allows transcription of cII and cIII, and both gpcII and gpcIII are necessary for repressor synthesis. gpcII functions as a positive regulator for the initiation of repressor synthesis from pRE (= pE ), being necessary for recognition of this promoter by RNA polymerase. gpcII is unstable in vivo owing to proteolysis by host proteins (products of the hflA and hflB genes being involved); this proteolysis is apparently inhibited by gpcIII and by cAMP–CAP. The establishment of lysogeny is favoured by certain environmental conditions, e.g., by starvation of cells prior to infection, and by a high multiplicity of infection (MOI). It has been suggested that starvation may increase cAMP–CAP levels, while high MOI increases levels of gpcIII (a gene dosage effect); in either case the result is stabilization of gpcII thus favouring lysogeny. Once synthesized, the repressor maintains its own synthesis by activating cI expression from an alternative promoter, pRM (= pM ); transcription from pRM can occur only when repressor is bound to oR . Translation of the pRM -initiated mRNA is much less efficient than that of the pRE -initiated mRNA. Thus, synthesis of repressor occurs at high levels by the pRE -dependent ‘establishment circuit’ and at lower levels by the pRM -dependent ‘maintenance circuit’. The repressor is antagonized by the product of the immediate early gene cro: gpcro (‘antirepressor’) prevents transcription of cI from pRM , and reduces (but does not eliminate) transcription of early genes from pL and pR [cro-operator and repressor–operator interaction: ARB (1984) 53 293–321]; thus gpcro prevents ‘maintenance synthesis’ of repressor and also (by reducing gpcII formation) ‘establishment synthesis’ from pRE . Sufficient early gene transcription persists to allow expression of Q and hence of the late genes, so that the lytic cycle can be completed. The lysis/lysogeny decision thus depends on whether gpcI or gpcro occupies the operators oR and oL ; this in turn depends largely on the level of gpcII (which also affects 77

bacteriophage M12 integration – see later) and hence is subject to influence by the host cell e.g. in response to environmental conditions. In Escherichia coli lysogeny involves integration of the phage cccDNA with the host chromosome. This occurs by SITE-SPECIFIC RECOMBINATION, i.e., by reciprocal recombination between specific ‘attachment sites’ – one on the phage genome (attP ) and one on the host genome (attB, also called att l , situated between genes gal and bio); each att sequence consists of a central ‘core’ sequence (O) which is common to both attB and attP, flanked by ‘arm’ sequences designated B and B′ for attB, P and P′ for attP. Integration requires the int gene product (integrase) and certain host proteins, including DNA gyrase and INTEGRATION HOST FACTOR, IHF. (IHF consists of two subunits, a and b: products of genes himA and himD (= hip), respectively.) Integrase recognizes attB and attP, while IHF recognizes only attP. Interaction between these recombination proteins, bound to their att sites, brings about recombination by the formation of a staggered break in the O region followed by strand exchange and ligation. The integrated prophage is thus flanked by hybrid att regions, attL (BOP′ ) and attR (POB′ ). The integration reaction is reversible, but while integration involves recognition between attP and attB, excision – the reverse reaction – requires recognition between attL and attR; excision requires an additional phage protein, the xis gene product (excisionase), which can bind to a specific region in the P arm of attP and attR [PNAS (1985) 82 997–1001]. The regulation of the reaction such that integration occurs preferentially under conditions which favour lysogeny, while excision occurs only on induction of a lysogen, is achieved by control of the amounts of integrase and excisionase available. The int gene can be transcribed from either of two promoters: pL and pI ; however, integrase is produced only during establishment of lysogeny and not during the lytic cycle. Under conditions which favour lysogeny, gpcII not only activates cI expression (hence preventing transcription from pL ), it also activates int expression from pI . (Since pI overlaps xis, transcription from this promoter allows expression of int without that of xis, thus favouring integration.) However, under lytic conditions – during which transcription proceeds from pL – int gene expression is prevented by RETROREGULATION: gpN-modified, pL -initiated transcription extends beyond int, through att, and into the b region; the b region contains a sequence (sib) which causes the 3′ end of the corresponding mRNA to adopt a secondary structure which is recognized and cleaved by RNase III (q.v.). This cleavage is followed by degradation of the transcript in the 3′ -to-5′ direction, thus preventing int expression. (Under conditions which favour lysogeny, the pI -initiated transcript, which terminates before the sib region, is a poor substrate for RNase III, and hence int expression can occur.) Induction of l may occur spontaneously (ca. 1 per 102 –105 lysogenic cells per generation); however, high levels of induction may be brought about by agents which damage DNA (e.g., UV irradiation, mitomycin C). Damage to DNA results in the ‘activation’ of the host RecA protein (see RECA PROTEIN), resulting in cleavage and inactivation of the repressor. (Levels of DNA damage necessary for l induction are higher than those required to induce the SOS SYSTEM; presumably gpcI becomes susceptible to RecA-mediated cleavage only when host cell viability is threatened.) Since the repressor functions as a positive regulator for its own synthesis, its inactivation also prevents the synthesis of replacement repressor molecules. Inactivation of the repressor allows transcription from pL and pR , followed by excision of the prophage and completion of the

events of the lytic cycle. In contrast to pL -initiated transcription in the lytic cycle, pL -initiated transcription in the prophage results in the expression of both int and xis (necessary for excision). This is possible because, owing to the permuted gene order in the prophage, the sib-containing b region is no longer immediately downstream from int; the pL -initiated transcript is thus not recognized by RNase III, and both int and xis can be expressed. [General review: Book ref. 79; l–host interactions: MR (1984) 48 299–325.] bacteriophage M12 See LEVIVIRIDAE. bacteriophage M13 See INOVIRUS. bacteriophage MS2 See LEVIVIRIDAE. bacteriophage Mu A temperate bacteriophage which can infect various enterobacteria (e.g. Escherichia coli, Citrobacter freundii, Erwinia spp, and certain mutant strains of Salmonella typhimurium). The phage particle has an icosahedral head (ca. 60 nm diam.) and a contractile tail (ca. 100 nm long when extended, 60 nm when contracted) to which is attached a base plate with spikes and tail fibres; the phage tail adsorbs to LPS in the outer membrane of a host cell. Phage particles contain linear dsDNA ca. 39 kb long. An early event after phage infection – regardless of whether infection will eventually result in a lytic cycle or the lysogenic state – is the integration of Mu DNA into the host chromosome at a more or less randomly selected location. Integration often results in the inactivation of the gene in which it occurs; ca. 2–3% of bacteria in a population acquire a recognizable mutation on lysogenization by Mu, a frequency much greater than the spontaneous mutation rate in the absence of Mu – i.e., Mu acts as a mutator phage (Mu = abbr. for mutator). The initial integration event may be conservative (i.e., both strands of the Mu DNA may be inserted) and appears to be a simple (nonreplicative) insertion; it requires the product of Mu gene A which can recognize and bind to the ends of Mu DNA [Cell (1984) 39 387–394]. Synthesis of a repressor (the c gene product) results in lysogeny and immunity to superinfection by Mu. During the lytic cycle, Mu DNA replication occurs entirely by repeated replicative transposition of the integrated DNA (which thus functions as a giant TRANSPOSON, causing chromosomal deletions, inversions, duplications etc); Mu DNA insertion results in a 5-bp duplication of the target DNA (cf. Tn3 ). Transposition occurs at very high frequency (ca. 100 transpositions per cell in ca. 30 min), copies of Mu DNA being inserted at random locations in the chromosome; this results in the death of the host cell, and ca. 100 progeny phages are released ca. 60 min after infection. Transposition is controlled by the products of phage genes A and B and requires continual synthesis of gpA – which apparently acts stoichiometrically; gpA functions as a transposase, gpB apparently functions in the modification of gpA activity. [Role of DNA topology in Mu transposition: Cell (1986) 45 793–800.] Phage Mu DNA contains three regions, designated a (ca. 33 kb), G (ca. 3 kb) and b (ca. 1.7 kb), flanked by random sequences of bacterial DNA (see below). The a region contains most of the phage genes, including e.g. the repressor (c) gene, all the early functions, all the head functions, and most of the tail functions. The G region carries the remainder of the tail functions and specifies the host range of the phage. The G segment is flanked by short inverted repeats, and can invert by reciprocal recombination between these sequences; when in one orientation, designated G(+), it specifies a host range which includes E. coli K12 strains, but in the alternative 78

bacteriophage P1 bacteriophage MV-L51 See PLECTROVIRUS. bacteriophage 06N 58P See CORTICOVIRIDAE. bacteriophage N4 A virulent coliphage of the PODOVIRIDAE. Genome: linear dsDNA (ca. 71 kb) containing terminal direct repeats 400–450 bp long and a 7-base 3′ overhang at one end. The phage particle contains a rifampicin-resistant DNAdependent RNA polymerase which is injected into the host cell with the DNA and which is necessary for transcription of N4 early genes. Transcription of intermediate (middle) genes requires the synthesis and activity of three N4 early proteins, two of which are components of a second rifampicin-resistant RNA polymerase; transcription of late genes requires E. coli RNA polymerase activity. Host DNA replication is blocked by an N4 early gene product, but host RNA and protein synthesis continues (except in the case of cAMP-dependent operons). The N4 genome codes for most functions required for its replication, including a DNA polymerase and DNA-binding protein; the only host functions it appears to require are gyrase, DNA polymerase 5′ → 3′ exonuclease activity, DNA ligase, and nrdA gene function [Book ref. 69, pp. 245–254]. bacteriophage P1 A temperate BACTERIOPHAGE (family MYOVIRIDAE) which infects Escherichia coli and Shigella spp. Virion: icosahedral head (ca. 90 nm diam.) with a long, complex contractile tail bearing a base-plate and tail fibres. Genome: dsDNA (MWt ca. 66 × 106 ), circularly permuted and terminally redundant. On infection of a host cell, the genome circularizes (with loss of redundancy) and may enter a LYTIC CYCLE or establish LYSOGENY. Relatively little is known about the lytic cycle; both q- and s-type modes of DNA replication occur early in infection, but later only s-type replication can be observed. DNA packaging occurs by a ‘headful’ mechanism, starting at a unique site (pac); cleavage of DNA at a pac site apparently occurs early in infection, before phage heads are formed, and the enzyme responsible may remain bound to the DNA and subsequently interact with a prohead to initiate packaging. (cf. BACTERIOPHAGE P22.) In the lysogenic state, the P1 prophage does not normally integrate into the host chromosome, but persists as an autonomous, circular PLASMID (P1 plasmid) which is maintained at one or two copies per host chromosome. The replication control system of the P1 plasmid resembles that of the F PLASMID (q.v.) e.g. in that it involves a plasmid-encoded protein (designated RepA in the P1 plasmid) which is essential for replication and which autoregulates its own synthesis. Moreover, the repA gene is flanked on each side by multiple 19-bp repeat sequences, and it appears that one of these multiple repeats (incA) may be involved in the control of copy number in that it appears to titrate the RepA protein. [P1 replication: JBC (1986) 261 3548–3555.] The P1 plasmids are segregated (see PARTITION) with great accuracy at each host cell division, and spontaneous loss of the plasmid is extremely rare. This high degree of accuracy involves several mechanisms. For example, P1 encodes a SITE-SPECIFIC RECOMBINATION (SSR) system which facilitates accurate partition by efficiently resolving plasmid dimers into monomers. (Dimers are formed by homologous recombination between the two plasmids resulting from replication.) This system involves a site (loxP ) on the plasmid at which SSR occurs, and a gene (cre) encoding the recombinase. (The lox-Cre system also catalyses cyclization of the phage genome on infection of the host – at least in RecA− hosts; it can also mediate the rare integration of the P1 plasmid into the host chromosome at a site designated loxB.) [Regulation of the cre gene: JMB (1986) 187 197–212.] Partition per se involves a sequence (par ) in the plasmid; a gene (parA)

G(−) orientation it specifies different tail fibres specific for a different host range. [Host cell receptors for Mu G(+) and G(−) types: FEMS (1985) 28 307–310.] (See also G LOOP and BACTERIOPHAGE P1.) A gene designated gin, in the b region adjacent to the G region, is essential for G inversion; gin encodes a site-specific recombination enzyme which is stimulated by a small, heat-stable host protein [BBA (1986) 866 170–177] and which apparently recognizes the inverted repeats flanking the G segment. In the lysogenic state, the G segment undergoes inversion at a slow but steady rate due to a low level of gin expression. The level of gin expression is thought to be about the same during the lytic cycle, but G inversion rarely has time to occur before the lytic cycle is complete; hence G loops are rarely observed in denatured/renatured Mu DNA in lysates from lytic infections. (See also RECOMBINATIONAL REGULATION.) In addition to gin, the b region also contains a gene (mom) which encodes a DNA modification function. The targets for this modification system are adenine residues in pentanucleotide sequences 5′ . . . (C/G)A(C/G)NPy . . . 3′ ; ca. 15% of the adenine residues in the Mu DNA are modified, the modified bases being N 6 -(1-acetamido)-2-deoxyadenosine. The modified DNA is resistant not only to the host restriction system in vivo but also to in vitro cleavage by a range of restriction endonucleases. The mom gene is apparently repressed in the prophage but is strongly expressed on induction; the host Dam methylase (product of the DAM GENE) is necessary for mom gene expression [mechanism: EMBO (1986) 5 2719–2728]. During phage assembly, Mu DNA is packaged by a ‘headful’ mechanism: packaging begins near the ‘left’ (c) end of the Mu DNA and continues until ca. 39 kb of DNA have been incorporated into the phage head. The Mu DNA itself is ca. 37.5 kb long; thus, the packaging mechanism results in a variable length of bacterial DNA at each end of the phage genome (on average ca. 50–100 bp at the c end, ca. 1700 bp at the ‘right’ or S end). These end sequences are random because of the random insertion of Mu DNA into the host chromosome; they appear as ‘split ends’ in phage DNA which has been denatured and reannealed. The ‘split ends’ are lost when the phage DNA integrates into a new host chromosome. (See also MINI-MU.) Mu can function as a generalized transducing phage, mediating gene transfer at frequencies of ca. 10−7 . Transduction by Mu can be detected only in rec+ recipient cells. The transducing particles, which contain only host DNA, probably arise by the rare packaging into Mu heads of host DNA instead of phage DNA. [Review: Book ref. 20, pp. 105–158; behaviour of Mu in Salmonella typhi : JGM (1986) 132 83–89.] bacteriophage m2 See LEVIVIRIDAE. bacteriophage MV-L1 See PLECTROVIRUS. bacteriophage MV-L2 (MVL2, L2 strain L2) A species of the PLASMAVIRIDAE. Host: Acholeplasma laidlawii ; plaques small, turbid. Genome: negatively supercoiled ds cccDNA (MWt ca. 7.8 × 106 ). Virion: roughly spherical, somewhat pleomorphic, (50−)80(−125) nm in diameter, sensitive to detergents, organic solvents, and heat (e.g. 60° C for 5 min). There is apparently no rigid helical or icosahedral nucleocapsid. The virion seems to consist of DNA condensed with protein and enclosed within a flexible, lipid-containing, ‘unit-type’ membrane apparently derived from the host cell membrane. Infection leads to lysogeny, the phage DNA becoming integrated with the host’s chromosome. Progeny virions are released by budding through the host cell membrane; lysis does not occur, and the host remains viable. bacteriophage MV-L3 See MV-L3 PHAGE GROUP. 79

bacteriophage P2 consists of an icosahedral head (ca. 60 nm diam.) attached via a short tubular ‘neck’ to a ‘tail’ which is essentially no more than a hexagonal base-plate bearing short spikes. The ‘tail’ region has endorhamnosidase activity. Genome: dsDNA (MWt ca. 26 × 106 ), terminally redundant, and circularly permuted in certain regions of the genome. On infection of a host cell, the linear DNA is circularized either by the host RecA system or by a general recombinase encoded by the P22 erf gene. In the lytic cycle, the DNA may undergo some replication in the circular form; subsequently, concatemers many unit genomes in length are produced. During virion assembly, a prohead consisting mainly of coat protein (gp5) and a SCAFFOLDING PROTEIN (gp8) interacts with a concatemeric DNA molecule; DNA is encapsidated, beginning at a specific site (pac) in the concatemer and proceeding sequentially until the head is full, and the scaffolding protein is eliminated intact (and is recycled). It appears that once the first packaging event has been completed, the remaining DNA of the concatemer is encapsidated by other proheads – i.e., the leading end of the DNA which enters the second and subsequent proheads is determined not by the pac site but by the length of DNA packaged by previous prohead(s). (The mechanism of this is uncertain; the initial cleavage at the pac site can apparently occur in the absence of encapsidation [JMB (1982) 154 565–579].) (cf. BACTERIOPHAGE P1.) Maturation of the virion requires the addition of certain minor phage proteins. (See also TRANSDUCTION.) The lysogenic pathway in P22 is essentially similar to that in l (see LAMBDOID PHAGES). The prophage inserts in the Salmonella chromosome at a site between proA and proC ; insertion is catalysed by a P22-specified integrase encoded by an int gene located close to the att site. bacteriophage PA2 See STYLOVIRIDAE. bacteriophage PBS1 A large, morphologically complex FLAGELLOTROPIC PHAGE (family MYOVIRIDAE) which infects Bacillus subtilis; its DNA contains deoxyuridine instead of thymidine. PBS1 is a pseudotemperate phage, establishing a carrier state in its host (see PSEUDOLYSOGENY); it can mediate transduction. bacteriophage PBSX A defective bacteriophage, the prophage of which is normally present in the chromosome of its host, Bacillus subtilis. When induced by mitomycin C, PBSX packages 13-kb lengths of DNA which may include sequences from any region of the host chromosome, packaging probably occurring by a ‘headful’ mechanism [JV (1985) 54 773–780]. bacteriophage Pf1 See INOVIRUS. bacteriophage Pf2 See INOVIRUS. bacteriophage fI See T7 PHAGE GROUP. bacteriophage fII See T7 PHAGE GROUP. bacteriophage f6 The sole member of the family Cystoviridae. Host: Pseudomonas syringae pv. phaseolicola; plaques clear, diam. 1–3 mm. Some strains of P. pseudoalcaligenes can be infected. The virion (diam. ca. 75 nm) has a segmented genome of three pieces of dsRNA designated L, M and S (MWt ca. 5.0, 3.1 and 2.3 × 106 , respectively). [Nucleotide sequence of, and translational control in, the S segment: JV (1986) 58 142–151.] The RNA occurs in a polyhedral inner particle (composed of proteins P1, P2, P4 and P7) which is covered with a layer of protein P8 – the whole forming the nucleocapsid (diam. ca. 60 nm). The nucleocapsid is surrounded by a phospholipid- and protein-containing envelope (P3, P5, P6, P9, ?P10) which can be removed (with loss of infectivity) by treatment with detergents. An RNA polymerase (P1, P2) is associated with the capsid. The virion also contains an enzyme (P5, ?P10) active against the host cell wall; this enzyme seems necessary both for penetration of the host and for the release of phage progeny.

within this sequence encodes a protein which may promote partition by binding to the plasmid at a particular site (incB ) and to (probably) the host cell envelope [JMB (1985) 185 261–272]. P1 also has a second SSR system which is responsible for the inversion of a 4.2-kb segment (the C segment) of the P1 genome. The C segment was first identified as a ‘C loop’ analogous to the G LOOP of bacteriophage Mu. The C segment of P1 and the G segment of Mu are homologous (each specifies different host ranges in different orientations), and their controlling elements (encoded by cin in P1, gin in Mu) can complement each other (see also RECOMBINATIONAL REGULATION). However, the inverted repeats at each end of the C segment are not homologous with those of the G segment. (Efficient inversion of the C segment apparently requires an additional cis-acting sequence, distinct from the cross-over sites cixL and cixR [PNAS (1985) 82 3776–3780].) [The P1 genome: JB (2004) 186 7032–7068.] bacteriophage P2 A temperate BACTERIOPHAGE (family MYOVIRIDAE) which infects Escherichia coli. The phage virion consists of an isometric head attached to a contractile tail. Genome: linear dsDNA (MWt ca. 22 × 106 ) which has 19-base STICKY ENDS. On infection of a host cell, the DNA forms closed circular molecules which, in lysogenic infections, can integrate into the host chromosome at a preferred site near the his operon; the phage ‘attachment site’ (attP ) occurs between genes int (encoding the P2 integrase) and ogr (see below). (cf. BACTERIOPHAGE LAMBDA.) P2 DNA replication occurs unidirectionally from a single origin near the right-hand end of the genome. Replication requires P2 genes A and B and (at least) host genes dnaB, polC and rep; P2 gpA is a (preferentially cis-acting) DNAbinding protein. The products of DNA replication are cccDNA monomers (i.e., concatemers are not formed). Expression of P2 late genes (which encode phage structural components) depends on the expression of the ogr gene, which in turn depends on P2 DNA replication. (cf. BACTERIOPHAGE P4.) During phage assembly, the DNA monomer undergoes staggered cleavage at a unique site (cos) to form the linear molecule with sticky ends characteristic of the P2 virion. bacteriophage P4 A satellite BACTERIOPHAGE (see SATELLITE VIRUS) which infects Escherichia coli and which requires all of the late genes of a helper phage such as BACTERIOPHAGE P2 to complete its replication cycle. The P4 genome is linear dsDNA (ca. 11.4 kb) with 19-nucleotide sticky ends which allow the DNA to circularize in the host cell. P4 DNA replication occurs bidirectionally from a single origin [JMB (1985) 182 519–527]; an early P4 gene product, gpa, is required for P4 DNA replication and is apparently a (rifamycin-resistant) primase [JMB (1985) 182 509–517]. In the absence of a helper phage, P4 can replicate its DNA and can lysogenize its host, but progeny virions can be formed only in the presence of a helper. In cells co-infected with P2 and P4, P4 capsids predominate and are assembled largely from P2 head proteins – although the P4 capsid is smaller than that of P2. P4 alters the regulation of transcription of P2 head proteins; the product of the P4 d gene is apparently a trans-acting accessory transcription factor which can substitute for P2 gpogr and thus circumvent the dependence of late P2 genes on P2 DNA replication [Book ref. 118, pp. 108–110]. bacteriophage P7 A BACTERIOPHAGE which is closely related to BACTERIOPHAGE P1; however, P1 and P7 are heteroimmune and differ in plasmid maintenance functions. bacteriophage P22 A temperate BACTERIOPHAGE (family PODOVIRIDAE) which infects Salmonella (smooth strains). The virion 80

bacteriophage fX174 The virion adsorbs (P3, P6) to the sides of the subpolar host pili; the f6 envelope fuses with the host outer membrane, and the nucleocapsid minus P8 enters the host cell. Inside the cell the phage RNA polymerase catalyses RNA synthesis; an ss mRNA, designated l (MWt ca. 2.2 × 106 ), is transcribed early and codes for P1, ?P2, P4 and P7. These four proteins form a 120S procapsid or previrion I which incorporates progeny dsRNA to form previrion II. (The synthesis of dsRNA is not understood, but it occurs within a subvirion structure. A model for the initiation of replication and transcription in bacteriophage f6 has been proposed [Nature (2001) 410 235–240].) Previrion II synthesizes ss mRNAs m and s (MWt ca. 1.4 and 1.1 × 106 , respectively); s codes for P8 and P9, m for P3, P6 and P10 (and possibly also P4 and P7.) Previrion II incorporates P8 to form the complete nucleocapsid. Finally, the lipoprotein envelope is added – apparently mediated by the (non-structural) phage protein P12; although the lipid is apparently derived from host phospholipid, the membrane is formed in the cytoplasm and not in contact with the cell membrane. Phage release occurs by host cell lysis. (Note: the name bacteriophage f6 has also been used for a pilus-dependent dsDNA phage of Caulobacter [JV (1980) 35 949–954].) bacteriophage f29 A BACTERIOPHAGE (family PODOVIRIDAE) which infects strains of Bacillus subtilis and those of certain other species of Bacillus. The virion has a complex morphology: an elongated head (ca. 32 × 42 nm), bearing protein fibres at each end, joined via a connector region to a short tail. Genome: linear dsDNA (ca. 18 kb) with 6-bp terminal inverted repeats. The 5′ end of each strand in the DNA genome is formed by a dAMP residue; each dAMP residue is linked covalently (via a phosphodiester bond) to a serine residue in a phage-encoded protein (gp3) – a so-called terminal protein (TP). The terminal proteins are essential for initiation of replication of the f29 genome. Replication of the linear f29 DNA is initiated at both ends of the molecule (not simultaneously); it involves a phageencoded DNA polymerase (gp2) which has exonuclease activity [NAR (1985) 12 1239–1249]. The polymerase binds to a free molecule of the TP, and this complex localizes at the 3′ end of each strand – perhaps by interacting with TP at the adjacent 5′ end. The polymerase then mediates a dATPdependent reaction in which dAMP is covalently linked to the complexed TP; this dAMP residue serves as a 3′ -OH primer. The polymerase begins strand synthesis (5′ -to-3′ ), and after insertion of nucleotide 10 the polymerase and TP dissociate from one another – the TP remaining covalently bound at the 5′ end of the new strand while the polymerase continues to extend the (DNA) primer. The polymerase is able to displace the (5′ -to3′ ) strand complementary to the template, and to achieve good processivity, without help from a helicase or from other factors [JBC (1996) 271 8509–8512]. Replication of the f29 genome is an example of so-called protein priming – only one example of the strategies used for replicating a linear genome. [Protein priming of DNA replication in phage f29: EMBO (1997) 16 2519–2527.] (See also ADENOVIRIDAE.) During phage assembly, the major coat protein (gp8) is assembled with the aid of a (re-cyclable) scaffolding protein (gp7) which is displaced as the DNA is incorporated. [Morphogenesis: JV (1985) 53 856–861.] The packaging of DNA into the phage head requires energy from ATP hydrolysis. It also requires certain phage-encoded RNA molecules designated pRNA. [DNA packaging: Cell

(1998) 94 147–150.] In a current model, a number of pRNA molecules form a (static) ring-shaped structure around a hole in the phage head through which the genome is inserted; the ˚ in length, with an axial connector (a dodecamer of gp10, 75 A channel) rotates, driven by ATP hydrolysis, and the ‘threaded’ (i.e. helical) DNA molecule enters the phage head like a bolt drawn through a nut when the nut is rotated [Nature (2000) 408 745–750]. Host cell lysis involves a phage-encoded peptidoglycandegrading enzyme; however, lysis also requires the product of phage gene 14 which is apparently a LYSIS PROTEIN [JB (1993) 175 1038–1042]. bacteriophage f80 See STYLOVIRIDAE and LAMBDOID PHAGES. bacteriophage f105 A temperate BACTERIOPHAGE which infects Bacillus subtilis (see STYLOVIRIDAE). The virion consists of an isometric head (ca. 52 nm diam.) attached to a flexible, noncontractile tail (ca. 220 nm long) which bears a baseplate with six appendages. Genome: dsDNA (MWt ca. 26 × 106 ), nonpermuted, apparently with sticky ends. During lysogeny, the phage DNA integrates at a specific attachment site in the host chromosome but, unlike e.g. BACTERIOPHAGE l, it appears not to circularize prior to integration, and the prophage is not circularly permuted with respect to the virion DNA; the mechanism of integration is not understood. On induction, f105 DNA apparently replicates in situ, together with adjacent regions of host DNA, and the phage DNA is subsequently excised from the newly synthesized molecules. LFT (but not HFT) lysates have been described; transduction appears to require that the recipient be a f105 lysogen. [Book ref. 170, pp. 251–256, 273–275.] bacteriophage fA See MICROVIRIDAE. bacteriophage fB See MICROVIRIDAE. bacteriophage fBA1 A temperate, tailed, dsDNA-containing BACTERIOPHAGE isolated from Bacillus aneurinolyticus. The virions apparently have a BACTERIOCIN-like killing activity against some strains of B. aneurinolyticus; this activity is independent of phage gene expression (phage DNA is rapidly degraded in the sensitive cells), and may be due to a proteinaceous component of the intact virion [JV (1986) 59 103–111]. (cf. BETACIN.) bacteriophage fC (1) See MICROVIRIDAE. (2) See STYLOVIRIDAE. bacteriophage fC31 A temperate bacteriophage originally isolated from Streptomyces coelicolor ; it can infect a wide range of Streptomyces spp. Genome: dsDNA (ca. 41.5 kb) with sticky ends. The prophage integrates in the host chromosome at a specific attachment site. bacteriophage fCbK See STYLOVIRIDAE. bacteriophage fD328 See STYLOVIRIDAE. bacteriophage fEC A tailed, temperate ACTINOPHAGE whose hosts are species of Rhodococcus; genome: linear dsDNA. fEC is inactivated by various lipid solvents. [Book ref. 73, pp. 216–218.] bacteriophage fK See MICROVIRIDAE and BACTERIOPHAGE G4. bacteriophage fNS11 See TECTIVIRIDAE. bacteriophage fR See MICROVIRIDAE. bacteriophage fW-14 A bacteriophage (family MYOVIRIDAE) which infects and lyses certain strains of Pseudomonas acidovorans. In fW-14 DNA ca. 50% of the thymine residues are hypermodified, occurring as a-putrescinylthymine; the hypermodified bases are apparently essential for the production of viable progeny phages – probably being required for DNA packaging [Virol. (1983) 124 152–160]. bacteriophage fX174 The type species of the MICROVIRIDAE (q.v. for morphology etc). After adsorption of fX174 to a host cell, the ss cccDNA phage genome penetrates the cell and is 81

bacteriophage fXahb bacteriophage PR5 See TECTIVIRIDAE. bacteriophage PR772 See TECTIVIRIDAE. bacteriophage PRD1 See TECTIVIRIDAE. bacteriophage Qb See LEVIVIRIDAE. bacteriophage R1 See STYLOVIRIDAE. bacteriophage R2 See STYLOVIRIDAE. bacteriophage R17 See LEVIVIRIDAE. bacteriophage R23 See LEVIVIRIDAE. bacteriophage 7S See LEVIVIRIDAE. bacteriophage S13 See MICROVIRIDAE and BACTERIOPHAGE fX174. bacteriophage SP3 See MYOVIRIDAE. bacteriophage SP6 A BACTERIOPHAGE which infects Salmonella typhimurium; it has a linear dsDNA genome (ca. 43.5 kb) and appears to resemble BACTERIOPHAGE T7 in its morphology and development. SP6 encodes a rifamycin-resistant RNA polymerase which is synthesized shortly after infection of a host cell. [Nucleotide sequence and expression of the cloned SP6 RNA polymerase gene: NAR (1987) 15 2653–2664.] bacteriophage SP8 See MYOVIRIDAE. bacteriophage SP50 See MYOVIRIDAE. bacteriophage SPb See STYLOVIRIDAE and BETACIN. bacteriophage SPO1 A virulent BACTERIOPHAGE which infects Bacillus subtilis. The virion consists of a large isometric head, containing >7 different polypeptides, joined via a complex connector structure to a contractile tail which terminates in a complex base-plate. The genome is a single molecule of linear dsDNA, MWt ca. 108 , which contains hydroxymethyluracil. [Review: Book ref. 170, pp. 218–245.] SPO1 is widely used in studies of transcriptional regulation in Gram-positive bacteria. Phage genes are expressed in three phases: early, middle and late. Early gene promoters are of the same type as those of host genes involved in vegetative functions, allowing transcription of early phage genes by the (unmodified) host RNA POLYMERASE. One early gene, gene 28, encodes a novel SIGMA FACTOR (sgp28 ) which replaces the host s43 (formerly known as s55 ), resulting in a holoenzyme which can recognize only phage middle promoters. Middle genes include genes 33 and 34, the expression of which is necessary for late gene transcription; gp33 and gp34 together replace the sgp28 in the RNA polymerase, resulting in an enzyme which – in the presence of the delta factor (see RNA POLYMERASE) – recognizes only late phage promoters, thus allowing the transcription of late genes (which encode phage structural components). (See also ENDOSPORE sense 1.) bacteriophage SPO2 A temperate BACTERIOPHAGE which infects Bacillus subtilis. Virion: an isometric head (ca. 50 nm diam.) attached to a tail ca. 180 nm long. Genome: dsDNA, MWt ca. 26 × 106 . [Book ref. 170, pp. 247–268 (256–259).] bacteriophage SPP1 See STYLOVIRIDAE. bacteriophage St-1 See MICROVIRIDAE and BACTERIOPHAGE G4. bacteriophage SV-C1 See SPIROPLASMAVIRUSES. bacteriophage SV-C2 See SPIROPLASMAVIRUSES. bacteriophage SV-C3 See SPIROPLASMAVIRUSES. bacteriophage T1 See STYLOVIRIDAE. bacteriophage T2 See T-EVEN PHAGES and MYOVIRIDAE. bacteriophage T3 A bacteriophage (family PODOVIRIDAE) which is very closely related to BACTERIOPHAGE T7. bacteriophage T4 A virulent enterobacterial (linear dsDNAcontaining) BACTERIOPHAGE – the best-known representative of the T-even phages. (See entry T-EVEN PHAGES for phage structure, nature of genome etc; see also MYOVIRIDAE.) The T4 infection cycle is initiated when the phage attaches, via the distal tips of its long tail fibres, to specific sites on the

coated with host SSB protein; a region between genes F and G (which can form hairpin loops) remains uncoated. Stage I (see SSDNA PHAGES) is dependent on host dnaB function (as it is in microviruses S13, G6, G13, G14 and fXahb – cf. BACTERIOPHAGE G4). A PRIMOSOME assembles at a specific n′ recognition sequence in the F–G intergenic region. The primosome migrates (5′ to 3′ ) along the n strand (displacing the SSB protein?), synthesizing primers at several sites. The c strand is completed as in other SSDNA PHAGES to form the ds RF (parental RF). It seems that most components of the primosome remain bound to the parental RF throughout this and subsequent stages, and that this obviates the need for supercoiling of the RF by gyrase – a step previously thought to be essential for initiation of stage II [PNAS (1981) 78 1436–1440]. Stage II: fX174 gpA nicks the n strand of the parental RF at a specific site in gene A and becomes covalently bound to the 5′ end of the nicked strand. The 3′ end is elongated by host DNA polymerase III holoenzyme in a ROLLING CIRCLE MECHANISM; ahead of holoenzyme action, the two RF strands are processively unwound by a complex of gpA and Rep protein. (The presence of gpA allows Rep protein to begin unwinding from the nick – not normally possible for HELICASES.) As synthesis proceeds, the displaced n strand (attached by its 5′ end to gpA at the replication fork) forms a growing loop which can function as template for the discontinuous synthesis of a c strand (primed by the conserved parental RF primosome components). When one genome length of n DNA has been displaced, it is excised and circularized by gpA and the c strand is completed to form the progeny RF. Progeny RFs are supercoiled by GYRASE and seem at this stage to function primarily as templates for transcription of phage genes. Stage III is closely coupled to phage morphogenesis. RFI (see RF) is cleaved by gpA, as in stage II, to form an RFII–gpA complex which, in the presence of gpC, associates with a procapsid (consisting of gpB, gpD, gpF , gpG and gpH ) to form a 50S particle. n strand synthesis and displacement seem to occur by a rolling circle mechanism; as the n strand is displaced, it is packaged within the procapsid. Packaging (but not phage DNA synthesis) requires gpJ , a component of the phage capsid [JV (1985) 54 345–350]. When a complete n strand has been displaced it is cleaved and circularized by gpA, releasing the RFII–gpA complex (for further rounds of n strand synthesis) and an SS cccDNA-containing immature phage particle; gpB and gpD are subsequently lost to form the mature 114S fX174 virion. bacteriophage fXahb See BACTERIOPHAGE fX174. bacteriophage fXtB See MICROVIRIDAE. bacteriophage PM2 The type species of the CORTICOVIRIDAE; host: Alteromonas espejiana BAL-31 (= Pseudomonas BAL31). The virion is icosahedral (diam. ca. 60 nm) and is sensitive to organic solvents and detergents; it comprises four major proteins, 12–14% by weight phospholipid, and supercoiled ds cccDNA (MWt ca. 6 × 106 ). The outer layer of the capsid is an icosahedral shell of protein PII (= sp27) with spikes of protein PI (= sp43) at the vertices. Within this is a lipid bilayer membrane whose composition reflects that of the host cell membrane at the time of phage assembly. The membrane seems to be associated with one or both of the remaining two proteins; these proteins may also be associated with the DNA, and at least one has transcriptase activity. Virions adsorb to the host cell wall. Maturation occurs at the cell periphery. The progeny are released by cell lysis. bacteriophage PP7 See LEVIVIRIDAE. bacteriophage PR3 See TECTIVIRIDAE. bacteriophage PR4 See TECTIVIRIDAE. 82

bacteriophage T7 host cell surface (see T-EVEN PHAGES). The tail fibres may occur in either of two states: extended or ‘retracted’ (i.e., folded back along the tail sheath and head); infection can occur only when the fibres are extended. Transition between the two states is affected by conditions: retraction (and hence loss of infectivity) is promoted by e.g. low pH, low temperature, low ionic strength, and in some strains by the absence of the adsorption cofactor tryptophan. Binding is initially reversible, but is followed by irreversible binding during which the base-plate undergoes a conformational change from a hexagonal form to an expanded, star-shaped structure with a central opening. This in turn triggers the contraction (by conformational change) of the tail sheath and the penetration of the host cell envelope by the inner tail tube. (Penetration may occur at ADHESION SITES.) The phage DNA is then transferred through the tail inner tube to the host cell. Since the inner tube tip appears to penetrate only as far as the outer surface of the host cytoplasmic membrane, DNA apparently does not enter the cytoplasm directly; uptake of the DNA by the host cell appears to require a membrane potential and can be inhibited by ionophores. Infection of the host cell is followed by transcription of the T4 DNA. This occurs in three main phases: early (immediate early and delayed early), middle, and late; each phase occurs at a distinct time after infection, is initiated at a distinct class of promoters, and requires a different transcription apparatus. The host RNA POLYMERASE is apparently used throughout, but undergoes a series of phage-induced alterations (e.g. ADPribosylation of first one, then both, of its a subunits) which affect its activity and affinities (e.g. for sigma factor); T4 gp55 is a SIGMA FACTOR which is necessary for the transcription of T4 late genes. Early effects on the host cell include the cessation of host DNA, RNA and protein synthesis (within 2–5 min of infection), unfolding of the host nucleoid, and degradation of host DNA by phage-coded nucleases specific for cytosine-containing DNA. The nucleotides thus released are used for the synthesis of progeny phage DNA. Late transcription is coupled to T4 DNA replication, which begins ca. 5 min after infection. Replication can be initiated at multiple origins [locations: JV (1985) 54 271–277] and occurs bidirectionally. It appears to be catalysed by a complex of phagecoded proteins (a ‘replisome’ – see DNA REPLICATION), including gp43 (DNA polymerase), gp32 (an SSB protein), gp44/45/62 (DNA polymerase accessory proteins which e.g. increase polymerase processivity and affinity for DNA), gpdda (a 5′ -to3′ helicase), and gp41 and gp61 (involved in the priming of Okazaki fragments). Leading strand synthesis is probably primed initially by host RNA polymerase. Okazaki fragments in lagging strand synthesis are primed by the formation of pentaribonucleotide primers (pppApCpNpNpN, where N = any of the 4 nucleotides) by gp41 and gp61; gp41 may be analogous to the DnaB protein of Escherichia coli (see DNAB GENE), while gp61 may be a PRIMASE. When elongation is complete, the 3′ end of the template for each lagging strand remains singlestranded; these single-stranded regions can ‘invade’ homologous regions of other phage DNA molecules, forming recombinational forks (see RECOMBINATION) and resulting in the formation of complex, branching, concatemeric intermediates. Resolution of the branches appears to require gp49 (T4 endonuclease VII). Later rounds of DNA replication may be initiated at recombinational forks, allowing replication to become independent of the (altered) host RNA polymerase. (Alteration of the RNA polymerase may prevent its recognition of origin promoters.) Modification of the DNA (glucosylation and methylation) occurs on the

completed polynucleotide strands; HMC substitution occurs at the level of precursor synthesis, involving hydroxymethylation of dCTP. Phage components are encoded by late phage genes. Heads, tail fibres and base-plates are each assembled by separate pathways. Head assembly involves at least 20 genes. Initially, a prohead is assembled on the host cytoplasmic membrane; the prohead consists of a shell surrounding a central core, the latter acting as scaffolding and controlling the assembly, size and shape of the prohead. When this structure is complete, nearly all of its constituent proteins undergo proteolytic cleavage, resulting in the removal of the core and the formation of a ‘cleaved prohead’. The cleaved prohead detaches from the membrane, and the main shell protein (gp23) undergoes extensive conformational changes which result in expansion of the prohead; this step is probably normally accompanied by DNA packaging. DNA is packaged by the ‘headful’ mechanism: one end of a linear concatemeric DNA molecule is inserted into the prohead, and the DNA continues to be incorporated until the head is full, when the DNA is cleaved (thus yielding the circularly permuted genome characteristic of T4). Base-plate assembly occurs by separate assembly of the hub and wedges (see T-EVEN PHAGES), followed by binding of the six wedges around the hub. The tail is then polymerized (inner tube first) on the base-plate. The completed tail structure associates spontaneously with the DNA-containing head, and finally the tail fibres and collar ‘whiskers’ are added. Progeny phages are released by lysis of the host cell. The mechanism of lysis is still not fully understood, but requires T4-coded LYSOZYME (gpe), the function of gene t (see LYSIS PROTEIN), and possibly gp5 (the base-plate hub lysozyme – see T-EVEN PHAGES). [Reviews on all aspects of T4: Book ref. 99.] bacteriophage T5 See STYLOVIRIDAE. bacteriophage T6 See T-EVEN PHAGES. bacteriophage T7 A virulent bacteriophage of the PODOVIRIDAE which infects Escherichia coli and other enterobacteria. Head: isometric, ca. 60 nm diam. [capsid architecture: Virol. (1983) 124 109–120]. Tail: ca. 17 nm long, with six short fibres; the distal end of the tail adsorbs to LPS in the outer membrane of a host cell. The T7 genome is a linear, non-permuted dsDNA molecule (ca. 40 kb) with terminally redundant ends (160 bp). T7 early genes constitute a single operon near the left end of the genome; these genes are transcribed by the host RNA polymerase and are concerned mainly with switching off host gene transcription and switching on transcription of T7 intermediate and late genes. (The large early-gene transcript is cleaved by host RNase III (q.v.) to give mRNAs.) Early gene products include a protein kinase (gp0.7), which phosphorylates and inactivates the host RNA polymerase (thus preventing further early gene transcription), and an RNA polymerase (gp1) which transcribes the T7 intermediate genes (concerned mainly with T7 DNA replication) and late genes (concerned with phage assembly and release of phage progeny by host cell lysis). Another phage product, gp2, also binds to and inactivates host RNA polymerase. The phage RNA polymerase is highly specific for T7 promoters; thus, by inhibiting host RNA polymerase, all transcriptional activity in the cell is switched to T7 DNA. [Organization and expression of T7 DNA: CSHSQB (1983) 47 999–1007.] Replication of T7 DNA (which remains linear throughout) is achieved mainly by proteins encoded by T7 DNA; it occurs in three stages: (i) Initiation occurs at a single site near the ‘left’ end of the genome. (Secondary sites can be used, 83

bacteriophage Tb although less efficiently, if the primary site is deleted.) The T7 gp1 RNA polymerase is necessary for initiation, apparently synthesizing a short primer from promoters in the initiation region. (ii) Bidirectional elongation (from the RNA primers) catalysed mainly by two phage-coded enzymes: gp5 and gp4. The protein gp5 combines with host THIOREDOXIN to form a DNA polymerase which synthesizes DNA on the RNA primers in the 5′ -to-3′ direction, thus forming the leading strands. The protein gp4 is a multifunctional enzyme with primase, helicase and NTPase activity; it binds to unwound ssDNA regions of parental DNA and translocates unidirectionally in the 5′ -to-3′ direction (driven by NTP hydrolysis), unwinding the parental strands ahead of the replication forks. As it encounters specific primase recognition sites in the DNA, gp4 synthesizes tetraribonucleotide primers (pppApCpCpC or pppApCpCpA) which provide the 3′ -OH ends necessary for initiation of lagging strand synthesis by the T7 DNA polymerase. [Book ref. 69, pp. 135–151.] Nucleotides for T7 DNA synthesis are provided by degradation of host DNA by T7 gp3 (an endonuclease) and gp6 (an exonuclease); gp6 (and/or host DNA polymerase I) may be involved in the removal of RNA primers. (iii) The newly synthesized daughter duplexes undergo recombination, probably mainly end-to-end, to form concatemers several times the length of a T7 genome [Virol. (1982) 123 474–479]; these concatemers undergo further rounds of replication. Each concatemer apparently contains only a single copy of the 160-bp terminal repeat sequence at the junctions between the genomes; the terminal repetition of the mature DNA is generated during maturation and packaging of the DNA into preformed prohead structures, when the concatemers are cleaved (possibly by gp3) into genome lengths. Mature progeny phages are released by host cell lysis (gp3.5 has lysozyme activity). Studies on the rate of internalization of the phage genome during infection have led to new insight into the mechanism by which the DNA of phage T7 is transferred to the bacterial cell. It appears that, following attachment, the phage ejects certain proteins which may form a channel across the bacterial cell envelope through which DNA is transferred; it has been speculated that two of the ejected proteins may be components of a ‘motor’ which rachets DNA into the host cell [Mol. Microbiol. (2001) 40 1–8]. bacteriophage Tb Syn. TBILISI PHAGE. bacteriophage typing See PHAGE TYPING. bacteriophage U3 See MICROVIRIDAE. bacteriophage v1 See PLASMAVIRIDAE. bacteriophage v2 See PLASMAVIRIDAE. bacteriophage v4 See PLASMAVIRIDAE. bacteriophage v5 See PLASMAVIRIDAE. bacteriophage v6 See INOVIRUS. bacteriophage v7 See PLASMAVIRIDAE. bacteriophage VP5 An ACTINOPHAGE of the STYLOVIRIDAE which infects Streptomyces coelicolor. bacteriophage W31 See T7 PHAGE GROUP. bacteriophage Xf See INOVIRUS. bacteriophage Xf2 See INOVIRUS. bacteriophage Z See BETACIN. bacteriophage ZJ/2 See INOVIRUS. bacteriophages See BACTERIOPHAGE. bacteriophagous Refers to organisms (e.g. certain protozoa) which consume bacteria. bacteriorhodopsin A hydrophobic, pigment-containing protein (MWt ca. 27000) which is the major protein constituent of the PURPLE MEMBRANE in Halobacterium salinarium; it

is involved in the (energy-generating) light-dependent transmembrane translocation of protons. The protein part of the bacteriorhodopsin molecule (apoprotein, bacterio-opsin) consists of seven membrane-spanning regions; the pigment – RETINAL – occurs within the space bounded by these seven regions, being linked to one of them via a lysine residue. Bacteriorhodopsin occurs in hexagonal arrays in the plane of the membrane. On illumination, bacteriorhodopsin undergoes a cyclical series of changes with a periodicity of ca. 5–10 msec, and this photocycling is associated with the pumping of protons from the inner (cytoplasmic) to the outer side of the membrane, i.e. generation of proton motive force (pmf). During photocycling at least five photointermediates appear to be formed; these are designated: K590 , L550 , M412 , N530 and O640 (the numbers being wavelengths, in nm, of maximum absorption). bR568 is the lightadapted ground state. Recent studies have clarified the mechanism, and route, of vectorial energy-dependent transport of protons across the membrane. Light induces the isomerization of (protonated) retinal from all-trans to 13-cis, isomerization resulting in deprotonation of the retinal – the proton being transferred to the asp-85 residue of the protein. Deprotonation of the retinal causes it to change conformation, and this, in turn, modifies the protein’s conformation – opening up a channel which permits entry of a proton from the cytoplasmic side of the membrane; this proton reprotonates residue asp-96 – the proton from asp-96 having been donated to reprotonate retinal. The proton on asp85 is transferred to the exterior of the membrane; this transfer appears to coincide with the N530 photointermediate. When incorporated into LIPOSOMES, bacteriorhodopsin tends (except at low pH) to adopt an orientation opposite to that in the cytoplasmic membrane – and hence to mediate inward pumping of protons. [Bacteriorhodopsin (overview): Nature (2000) 406 569–570. Structural changes in bacteriorhodopsin coupled to proton transport: Nature (2000) 406 645–648. Structural alterations in the M state: Nature (2000) 406 649–652. Molecular mechanism of vectorial proton translocation: Nature (2000) 406 653–657.] bacterioruberins C50 CAROTENOID pigments which occur in members of the HALOBACTERIACEAE. bacteriostatic (bacteristatic) Able to inhibit the growth and reproduction of at least some types of bacteria. (cf. BACTERICIDAL.) bacteristatic Syn. BACTERIOSTATIC. bacterium See BACTERIA. Bacterium A bacterial genus which has been obsolete for decades; various bacteria, e.g. Escherichia coli, Clostridium chauvoei etc., were once referred to as B. coli, B. chauvoei etc. bacterium-associated haemophagocytic syndrome (BAHS) See HAEMOPHAGOCYTIC SYNDROME. bacteriuria The presence of bacteria in the urine. bacterivore Any organism (e.g. a ciliate or amoeba) which ingests bacteria as its main or sole source of nutrients. (cf. e.g. DETRITIVORE.) bacterization The process of coating seeds, tubers etc. with certain bacteria (e.g. Azotobacter), prior to planting, with the object of improving plant growth. bacteroid A bacterium-like cell or a modified bacterial cell – see e.g. ROOT NODULES. (In an ACTINORRHIZA, ‘bacteroid’ may refer e.g. to a senescent hyphal fragment.) Bacteroidaceae A family of (typically) Gram-negative, anaerobic, chemoorganotrophic, asporogenous, motile and non-motile, 84

Baculoviridae typically rod-shaped or filamentous bacteria, some of which are pathogenic in man and other animals. Genera: ACETIVIBRIO, ANAEROBIOSPIRILLUM, ANAEROVIBRIO, BACTEROIDES, BUTYRIVIBRIO, FUSOBACTERIUM, LACHNOSPIRA, LEPTOTRICHIA, PECTINATUS, SELENOMONAS, SUCCINIMONAS, SUCCINIVIBRIO and WOLINELLA. In some of these organisms (e.g. Acetivibrio, Butyrivibrio, Lachnospira) the CELL WALL appears to resemble the Gram-positive (rather than Gram-negative) type of wall; since these organisms give a negative or variable reaction in the Gram stain (at least under some conditions) they have been grouped with the frankly Gram-negative genera [Book ref. 22, pp. 602–662]. Bacteroides A genus of Gram-negative bacteria (family BACTEROIDACEAE) which occur e.g. in the RUMEN and in the mouth and intestinal tract in man and other animals; some species are opportunist pathogens, being isolated from abscesses and other types of lesion (see e.g. FOOT-ROT; PNEUMONIA (f); SCALD). (See also ANAEROBIC DIGESTION; TERMITE–MICROBE ASSOCIATIONS; WETWOOD.) Cells: typically rods or filaments, nonmotile or peritrichously flagellated, sometimes with central or terminal swellings or vacuoles. Some species form a dark or black pigment. [Black-pigmented strains from animals: JAB (1983) 55 247–252.] Metabolism is typically fermentative, though some strains can carry out FUMARATE RESPIRATION in media containing haemin – electron donors including formate and H2 . Most species (‘fermentative’, ‘saccharoclastic’ or ‘saccharolytic’ species) typically attack a range of sugars, producing a mixture of products which may include acetic, formic, lactic, propionic and succinic acids; such species usually use or need CO2 – which is assimilated by the reductive carboxylation of succinate to 2-oxoglutarate. Other species attack sugars weakly, or not at all, but utilize peptones with the formation of mixtures of either small amounts of e.g. acetic, formic, lactic and succinic acids, or mixtures of larger amounts of e.g. acetic, butyric, propionic and succinic acids – isobutyric and isovaleric acids being formed whenever butyric acid is formed. Primary isolation may be carried out on media containing e.g. peptone, yeast extract, haemin and menaquinone under at least 5% CO2 . GC%: ca. 28–61. Type species: B. fragilis. B. endodontalis. A non-saccharolytic, black-pigmented species isolated from the dental root canal [IJSB (1984) 34 118–120]. B. fragilis (formerly Fusiformis fragilis). Cells (in glucose broth): non-motile round-ended rods, 0.8–1.3 × 1.6–8.0 µm. Catalase +ve (most other species are catalase −ve). Saccharolytic; in haemin-containing media some strains form a b-type cytochrome and can carry out fumarate respiration. On horse- or rabbit-blood agar colonies are typically smooth, round, entire, low convex, grey and non-haemolytic; some strains produce clear (‘b’) haemolysis. Optimum growth temperature: 37° C. B. fragilis may be sensitive to e.g. CEFOXITIN and clindamycin (see LINCOSAMIDES). (The ‘B. fragilis group’ commonly includes former subspecies of B. fragilis which are currently classified as species: B. distasonis, B. ovatus, B. thetaiotaomicron and B. vulgatus.) B. melaninogenicus. A saccharolytic species which forms a black pigment (a haem derivative) and which has SOD activity; it occurs e.g. in the human mouth. B. nodosus. A non-motile, non-saccharolytic species which causes foot-rot in sheep. [Surface structure and virulence of B. nodosus: JGM (1983) 129 225–234.] B. ochraceus. See CAPNOCYTOPHAGA.

B. pneumosintes (formerly Dialister pneumosintes). A nonsaccharolytic species which occurs e.g. in the human nasopharynx and which may be a secondary invader in upper respiratory tract infections. Cells: typically 0.2–0.4 × 0.3–0.6 µm. B. ruminicola. A saccharolytic species which ferments a wide range of carbohydrates, including e.g. cellobiose and starch; it occurs in the RUMEN. B. succinogenes. A saccharolytic rumen species which attacks relatively few sugars but which can utilize cellobiose and cellulose; unlike B. ruminicola, this species does not digest gelatin or hydrolyse aesculin. B. termitidis (formerly Sphaerophorus siccus var. termitidis). A saccharolytic species which occurs in the intestinal tract in termites. Other species: B. amylophilus, B. asaccharolyticus, B. bivius, B. buccae, B. capillosus, B. coagulans, B. corporis, B. denticola, B. disiens, B. distasonis, B. eggerthii, B. furcosus, B. gingivalis, B. gracilis, B. hypermegas, B. intermedius, B. levii, B. loescheii, B. macacae, B. microfusus, B. multiacidus, B. oralis, B. oris, B. ovatus, B. praeacutus (cf. TISSIERELLA), B. putredinis, B. splanchnicus, B. thetaiotaomicron, B. uniformis, B. ureolyticus, B. vulgatus and B. zoogleoformans. [Book ref. 22, pp. 604–631; Bacteroides of the human lower intestinal tract: ARM (1984) 38 293–314.] Bacto The designation of products of Difco Laboratories Inc., Detroit, USA. bactoprenol (undecaprenol) In bacteria: a lipid-soluble, membrane-bound polyprenol consisting of a linear chain of 11 unsaturated isoprene units: H−[CH2 .C(CH3 )=CH.CH2 ]11 −OH Bactoprenol phosphate acts as a carrier in the synthesis of a number of cell envelope and extracellular polymers: e.g., PEPTIDOGLYCAN, LIPOPOLYSACCHARIDE, TEICHOIC ACIDS and certain CAPSULE polymers; it apparently facilitates the transfer of lipophobic sugar residues across the cytoplasmic membrane. (cf. DOLICHOL; see also TUNICAMYCIN.) Baculoviridae A family of ccc dsDNA-containing VIRUSes which infect arthropods (particularly insects of the Diptera, Hymenoptera and Lepidoptera). Baculovirus virions are structurally complex, consisting of one or more nucleocapsids within an envelope; virions containing one nucleocapsid per envelope are rod-shaped, ca. 200–400 × 40–60 nm. The genome is nonsegmented circular supercoiled dsDNA, MWt ca. 58–110 × 106 . The family is divided (on morphological criteria) into three subgroups: A (the NUCLEAR POLYHEDROSIS VIRUSES, NPVs), B (the GRANULOSIS VIRUSES, GVs), and C. (cf. POLYDNAVIRIDAE.) The NPVs and GVs are characterized by the formation of intracellular crystalline protein occlusion bodies within which virions are embedded; the NPVs form polyhedral intranuclear occlusion bodies (called POLYHEDRA), each containing many virions, while the GVs form ellipsoidal or round-ended rod-shaped occlusion bodies (called ‘granules’ or ‘capsules’), each containing only one (rarely two) virions. The matrix proteins of both types of occlusion body (called polyhedrin, or polyhedrin in NPVs and granulin in GVs) are closely related in structure and function [review: JGV (1986) 67 1499–1513], but are apparently unrelated to the polyhedrins of the CYTOPLASMIC POLYHEDROSIS VIRUS GROUP. In contrast to the NPVs and GVs, baculoviruses of subgroup C do not form occlusion bodies; viruses of this subgroup have been observed in various arthropods (insects, arachnids, crustacea), the type species of the subgroup being Oryctes rhinoceros virus (from the coconut palm rhinoceros beetle). 85

baculoviruses An insect becomes infected with an NPV or GV when it ingests an occlusion body; the polyhedrin dissolves in the alkaline contents of the insect’s midgut, releasing virions which then infect cells of the midgut. Non-occluded virions produced in these cells bud through the plasma membrane of the midgut cells and are disseminated via the haemolymph, subsequently infecting cells of a wide range of tissues. The virion-containing occlusion bodies are formed late in infection, and are eventually released by the death and dissolution of the insect host. Baculoviruses have been extensively used for the BIOLOGICAL CONTROL of insect pests; they are particularly suitable for this purpose since they have no apparent relationship with any other known animal or plant viruses (and are therefore deemed unlikely to infect mammals or plants), and they can be lethal for – and spread rapidly among – insects in nature. Thus, e.g., NPVs have been used to control the European pine sawfly (Neodiprion sertifer ) and European spruce sawfly (Gilpinia hercyniae), GVs have been used against the Small White butterfly (Artogeia (= Pieris) rapae, a pest of crucifers), and Oryctes rhinoceros virus has been used successfully to control the coconut palm rhinoceros beetle. Since NPVs and GVs produce large quantities of polyhedrin/granulin in infected cells, the genomes of these viruses are of interest as vectors for the introduction and high-level expression of foreign genes in insects or insect cell cultures; e.g., a recombinant baculovirus containing a human a-interferon gene linked to the polyhedrin promoter yielded large quantities of a-interferon in silkworms [Nature (1985) 315 592–594]. baculoviruses Viruses of the BACULOVIRIDAE. Badhamia See MYXOMYCETES. BaeI See RESTRICTION ENDONUCLEASE (table). baeocyte A small, spherical reproductive cell (diam. ca. 2–3 µm) formed by members of section II of the CYANOBACTERIA. Baeocytes (formerly termed ‘endospores’) are produced by multiple fission of a vegetative cell which is enclosed in a fibrous layer external to the outer membrane of the cell wall; numerous baeocytes are released on rupture of the fibrous layer. A baeocyte enlarges, without division, until it reaches the size of a vegetative cell, this growth being accompanied by a progressive thickening of the fibrous outer layer. Gliding motility may be exhibited initially by those baeocytes which lack a fibrous outer layer at the time of their release. Baeomyces A genus of LICHENS (order LECANORALES); photobiont: e.g. Myrmecia. Thallus: crustose to squamulose, often sorediate. Fruiting bodies are non-lichenized, stalked, convex hymenial discs resembling miniature mushrooms (cf. PODETIUM). Species occur on soil, rocks etc. BAF See SEWAGE TREATMENT. bagassosis An EXTRINSIC ALLERGIC ALVEOLITIS associated with inhalation of the dust of sugar cane waste (bagasse); certain bacteria (e.g. Thermoactinomyces sacchari ) have been implicated. BAHS (bacterium-associated haemophagocytic syndrome) See HAEMOPHAGOCYTIC SYNDROME. bakanae disease (‘foolish seedling disease’; ‘foolish rice’) A disease of rice caused by Gibberella fujikuroi (Fusarium moniliforme) and characterized by conspicuous elongation of the plant stems (internodes) followed by wilting. The symptoms are believed to be due to the effects of GIBBERELLINS produced by the pathogen. (See also CEREAL DISEASES.) baker’s yeast A specialized strain of Saccharomyces cerevisiae which is capable of rapid fermentative activity in dough (see BREAD-MAKING), i.e., under conditions of low oxygen tension, low water activity, and high osmotic pressure. The yeast is manufactured by batch culture (in a medium containing molasses,

vitamins, minerals and a nitrogen source) for 12–18 hours at ca. 30° C with full aeration (to suppress fermentation). The yeast is harvested by centrifugation, washed, and concentrated by pressing or filtration. ‘Fresh yeast’ is blended, extruded, cut into cakes and wrapped; it can be stored for only a few days. ‘Active dry yeast’ is usually dried in a stream of warm air and sold as granules (water content ca. 8.0%); it can be stored for up to ca. 18 months in sealed containers. baking See BREAD-MAKING. BAL British anti-Lewisite: 2,3-dimercaptopropanol; in the presence of oxygen BAL acts as a mitochondrial RESPIRATORY INHIBITOR, apparently blocking electron flow between cytochromes b and c1 in Complex III of the ELECTRON TRANSPORT CHAIN. Balamuthia mandrillaris A species of amoeba which can cause ENCEPHALITIS in the young, old and immunocompromised. Trophozoites, 15–60 µm diam., have a round nucleus and a large, strongly staining nucleolus; cysts are roughly spherical, ca. 6–30 µm diam. [B. mandrillaris infection: JMM (2001) 50 205–207.] balanced growth See GROWTH. balanced salt solution (BSS) Any of several solutions used (with or without supplement) e.g. in TISSUE CULTURE to provide satisfactory ionic, pH and osmotic conditions for the maintenance and/or growth of cells (see e.g. EARLE’S BSS and HANKS’ BSS). Antibiotic(s) may be added to suppress microbial growth. (See also TRANSPORT MEDIUM; DULBECCO’S PBS; EAGLE’S MEDIUM.) Balanosporida See STELLATOSPOREA. Balansia See CLAVICIPITALES. balantidiasis See DYSENTERY (c). Balantidioides See HETEROTRICHIDA. Balantidium A genus of parasitic ciliate protozoa of the order TRICHOSTOMATIDA. B. coli can cause dysentery (see DYSENTERY (c)) in man, and is the only ciliate known to be pathogenic for man; it normally occurs e.g. as a harmless parasite in the intestinal tract in pigs. The trophozoite is ovoid with a tapering anterior end, ca. 40–70 µm in length, and is covered by spirally arranged longitudinal rows of cilia; the organism exhibits a rotatory movement. At the anterior end of the cell there is a deep invagination (the vestibulum) leading to the cytostome, and a smaller invagination (the cytopyge) occurs at the posterior end. The cell contains a large, kidney-shaped macronucleus (generally visible only in stained preparations) and a small micronucleus situated close to it; contractile vacuoles may be present. Reproduction occurs by binary fission; conjugation also occurs. Encystment occurs in the gut; the spherical cyst (ca. 50 µm diam.) contains a large macronucleus which can be seen in unstained preparations or in preparations stained with a solution of methyl green in dilute acetic acid. Trophozoites can be cultured in media which support the growth of parasitic intestinal amoebae. BALB/c mice An inbred mouse strain predisposed to MYELOMA formation on intraperitoneal injection of e.g. mineral oil. [The BALB/c mouse – genetics and immunology: CTMI (1985) 122 1–253.] Ballerup–Bethesda group (1) Strains of Citrobacter freundii which ferment lactose slowly. (2) Citrobacter freundii. ballistoconidium See BALLISTOSPORE. ballistospore A spore which, at maturity, is forcibly projected from its site of attachment on the sporophore; ballistospores are formed by many basidiomycetes (cf. BASIDIOSPORE), by some imperfect fungi (e.g. Sporobolomyces) and by slime moulds of the PROTOSTELIOMYCETES. (cf. STATISMOSPORE and GASTEROID 86

Bartonella BASIDIOSPORE.)

An asexually-derived ballistospore is sometimes referred to as a ballistoconidium. The ballistospore of a basidiomycete is formed terminally and asymmetrically on a sterigma; its surface is readily wettable. Shortly before discharge, a drop of liquid appears on the surface of the spore in a region near the attachment site (e.g. the HILAR APPENDIX); the drop grows in size (for ca. 5–40 sec) until, suddenly, both spore and drop are projected from the sterigma. [Proposed mechanisms for ballistospore discharge in Itersonilia perplexans: TBMS (1984) 82 13–29.] ballotini Small glass beads, obtainable in a range of sizes, used e.g. for the ballistic disintegration of cells; for this purpose, cells and Ballotini are shaken together in e.g. a BRAUN MSK TISSUE DISINTEGRATOR. Baltimore classification An early system of virus classification, proposed by Baltimore [Bact. Rev. (1971) 35 235–241], based on the nature of the genome and the strategy for viral gene expression (see VIRUS). Six classes (groups) were distinguished. I. dsDNA viruses. II. ssDNA viruses (only positive-sense ssDNA were known at the time). III. dsRNA viruses. IV. Positive-sense ssRNA viruses. V. Negative-sense ssRNA viruses. VI. RNA viruses in which DNA is synthesized (by reverse transcription) from the genome, and mRNA is transcribed from the DNA. (More classes would now be required to accommodate current knowledge of viral strategies.) bamboo mosaic virus See POTEXVIRUSES. BamHI A RESTRICTION ENDONUCLEASE from Bacillus amyloliquefaciens; G/GATCC. banana bunchy top virus See LUTEOVIRUSES. banana leaf spot (sigatoka disease) A disease of the banana plant (Musa) characterized by leaf lesions and imperfect development of the fruit; causal agent: Mycosphaerella musicola. The disease has been controlled by spraying with copper compounds or with mineral oil. band centrifugation See CENTRIFUGATION. Bangia See RHODOPHYTA. Bang’s disease See BRUCELLOSIS. bank (gene bank) Syn. LIBRARY. Banzi virus See FLAVIVIRIDAE. bar A unit of pressure equal to 100 kPa (cf. PASCAL). barban 4-Chlorobut-2-ynyl-3-chlorophenylcarbamate: a compound used e.g. for the control of wild oats; it also acts as a NITRIFICATION INHIBITOR. barbital (barbitone) 5,5′ -Diethylbarbituric acid. (Barbituric acid = malonylurea.) barbone Syn. HAEMORRHAGIC SEPTICAEMIA (2). Barbour Stoenner Kelly medium See BORRELIA (B. burgdorferi ). Barbulanympha See HYPERMASTIGIDA. bark-boring beetles See SCOLYTIDAE. bark necrosis See CANKER. barley B-1 virus See POTEXVIRUSES. barley diseases See CEREAL DISEASES. barley stripe mosaic virus See HORDEIVIRUSES. barley yellow dwarf virus See LUTEOVIRUSES. barley yellow mosaic virus See POTYVIRUSES. barley yellow striate mosaic virus See RHABDOVIRIDAE. Barmah Forest virus See ALPHAVIRUS. baroduric Syn. BAROTOLERANT. barophile An organism which grows optimally or obligately under elevated hydrostatic pressure; under atmospheric pressure (101.325 kPa) some barophiles (e.g. Shewanella benthica) continue to grow (less vigorously) but others (obligate

barophiles) die at a temperature-dependent rate. Barophilic bacteria in seas and oceans occur both in the nutrient-poor seawater and in the relatively nutrient-rich guts of invertebrates (e.g. holothurians – sea cucumbers); those occurring in cold regions (1 may be called AT types; GC types have a base ratio 50 µm in diameter. The organisms appear to be chemoorganotrophic heterotrophs, although at least some strains may be able to grow mixotrophically using sulphide as an electron donor; refractile ‘intracellular’ granules of sulphur (located between cytoplasmic membrane and cell wall) are formed in the presence of sulphide. Metabolism is respiratory, and a complete TCA cycle is present. Most strains can use acetate and/or lactate as the sole source of carbon; none can use hexoses. The main storage product is poly-b-hydroxybutyrate; volutin is also formed. [Review: ARM (1983) 37 341–354.] Beggiatoaceae See CYTOPHAGALES. Beijerinckia A genus (incertae sedis) of Gram-negative, aerobic, catalase-positive, chemoorganotrophic, asporogenous bacteria which occur e.g. in the phyllosphere and in soils (particularly in the tropics). Cells: typically round-ended rods, ca. 0.5–1.5 × 1.7–4.5 µm, peritrichously flagellated or non-motile; division involves constriction. Each cell characteristically contains two PHB-containing polar bodies. In some species each cell may be encysted, or several cells may occur within a single capsule. Metabolism is respiratory (oxidative), with O2 as terminal electron acceptor. NITROGEN FIXATION is carried out under both atmospheric and microaerobic conditions; in many strains N2 is used in preference to NO3 − . All strains can utilize glucose, fructose and sucrose as carbon sources; peptone does not support growth. Slime (sometimes elastic) is commonly formed, particularly on agar under N2 -fixing conditions. Colonies are often some shade of pink, or orange to pale brown. No pellicle is formed on liquid media. Optimum growth temperature: 20–30° C; no growth at 37° C. Growth can occur within the pH range ca. 3–10. GC%: ca. 55–61. Type species: B. indica; other species: B. derxii, B. fluminensis and B. mobilis. [Book ref. 22, pp. 311–321.] bell morels The fruiting bodies of VERPA spp. belladonna mottle virus See TYMOVIRUSES. benalaxyl See PHENYLAMIDE ANTIFUNGAL AGENTS. Beneckea An obsolete bacterial genus, members of which are now included in the genus VIBRIO. benign (med.) (1) (of disease) Mild; self-limiting; not recurrent. (2) (of tumours) Not MALIGNANT (sense 2). benign enzootic paresis Syn. TALFAN DISEASE. benign foot-rot (of sheep) See SCALD. 91

benign tertian malaria benign tertian malaria See MALARIA. Benlate See BENOMYL. benomyl (methyl-(1-n-butylcarbamoyl)-benzimidazole-2-carbamate; trade name: e.g. Benlate) An agricultural ANTIFUNGAL AGENT (see BENZIMIDAZOLES (a)). Benomyl is a systemic antifungal agent which has both eradicant and protectant properties against a wide range of plant diseases (e.g. many powdery mildews, apple scab, botrytis, eyespot of wheat and barley, black spot of roses); when used as a seed dressing it protects against seed-borne diseases such as smuts and bunts of cereals, and when mixed with a dithiocarbamate such as maneb or mancozeb it gives some control against glume blotch in wheat and against some cereal rusts. It is also used to prevent storage rots of fruit and vegetables (see e.g. GANGRENE sense 2). Benomyl owes its activity to its degradation, in solution, to the fungitoxic substances MBC (see BENZIMIDAZOLES) and butyl isocyanate; it also acts as a cutinase inhibitor, preventing penetration of the plant cuticle by the pathogen (see CUTIN) [Book ref. 58, pp. 94–95]. Benomyl-resistant strains of many fungal pathogens have emerged, reducing the usefulness of the fungicide in agriculture. [Bacterial degradation of benomyl: AvL (1978) 44 283–292, 293–309.] benquinox (1,2-benzoquinone-N ′ -benzoylhydrazone-4-oxime) A QUINONE ANTIFUNGAL AGENT which is used mainly as a seed dressing. Benson–Calvin–Bassham cycle Syn. CALVIN CYCLE. benthic Refers to the mud, sand etc, and/or to the indigenous organisms, at the bottom of a lake, sea or other body of water. (cf. PELAGIC; see also LITTORAL.) benzalkonium chloride See QUATERNARY AMMONIUM COMPOUNDS and e.g. KLEINSCHMIDT MONOLAYER TECHNIQUE. benzene Aerobic degradation: see HYDROCARBONS. Degradation in an anoxic environment: see BIOREMEDIATION. benzethonium chloride See entry QUATERNARY AMMONIUM COMPOUNDS. benzidine test A test used to detect bacterial CYTOCHROMES. Colonies of the test strain are flooded with a reagent consisting of benzidine dihydrochloride dissolved in a mixture of acetic acid and ethanol; on addition of an equal volume of H2 O2 (5%), cells which contain cytochromes develop a green or blue–green coloration. (cf. OXIDASE TEST.) benzimidazoles (a) (as antifungal agents) An important group of agricultural systemic ANTIFUNGAL AGENTS; they are often called ‘MBC fungicides’ because many of them decompose in aqueous solution (or in the plant) to form methyl benzimidazol-2-yl carbamate (MBC, CARBENDAZIM) – apparently the primary fungitoxic agent. MBC appears to act primarily in the nucleus where it disrupts the formation of spindle microtubules, inhibiting or disrupting mitosis. Single-step resistance to benzimidazoles tends to emerge readily. The group includes BENOMYL, CARBENDAZIM, FUBERIDAZOLE, THIABENDAZOLE and THIOPHANATE-METHYL. (b) (as antiviral agents) See e.g. ENVIROXIME and HBB. benzoic acid (C6 H5 COOH) An antibacterial and antifungal ORGANIC ACID used (as the free acid or as benzoate) as a PRESERVATIVE (e.g. in fruit juices, cordials, sauces, acidic foods, pharmaceuticals) and, with other agents, for the topical treatment of certain fungal infections; it is maximally effective below ca. pH 5, activity decreasing sharply with increase in pH above this value. Benzoic acid can be inactivated by certain colloids (e.g. kaolin). (cf. PARABENZOATES.) benzoquinones See QUINONES. benzoyl peroxide See ACNE. benzyl alcohol See ALCOHOLS.

2-benzyl-4-chlorophenol See PHENOLS. benzylpenicillin (penicillin G) One of the first of the natural PENICILLINS to be produced (from e.g. P. chrysogenum); R = C6 H5 .CH2 .CO (see b-LACTAM ANTIBIOTICS). It is active against many Gram-positive bacteria which do not produce bLACTAMASES, but is poorly active against Gram-negative species. It is administered parenterally. Berenil A trypanocidal DIAMIDINE which binds to AT-rich regions of dsDNA (apparently in the same way as does NETROPSIN). beriberi (acute cardiac) See CITREOVIRIDIN. Berkefeld candle See FILTRATION. Berne virus An enveloped RNA virus (proposed family: TOROVIRIDAE) isolated from a horse. The virion is pleomorphic (ca. 120–140 nm diam.) and consists of an elongated, curved nucleocapsid enclosed by a peplomer-bearing envelope. The genome is a single molecule of positive-sense ssRNA (MWt ca. 6 × 106 ); polyadenylated subgenomic mRNAs are apparently synthesized in infected cells. Maturation apparently involves the budding of preformed tubular nucleocapsids into Golgi vesicles and intracytoplasmic cisternae; the nucleocapsid appears to undergo a morphological change during budding [JGV (1986) 67 1305–1314]. Berry–Dedrick phenomenon See NON-GENETIC REACTIVATION. Besnoitia A genus of coccidian protozoa (suborder EIMERIORINA); members are classified by some authors [AP (1982) 20 403–406] in the genus ISOSPORA. The organisms are parasitic in a range of animals – e.g. cattle, horses, sheep, cats, rodents; transmission may occur e.g. via blood-sucking flies or by ingestion of infected tissues. Disporic, tetrazoic oocysts are formed. b (duplex winding number) See DNA. b-barrel pore See PROTEIN SECRETION (type IV systems). b-exotoxin Syn. THURINGIENSIN. beta interferon See INTERFERONS. beta-lactam antibiotics See b-LACTAM ANTIBIOTICS. beta-lactamases See b-LACTAMASES. b operon See RIBOSOME (biogenesis). beta-rays See IONIZING RADIATION. Betabacterium See LACTOBACILLUS. betacin A BACTERIOCIN-like, heat-resistant, proteinaceous substance produced by bacteriophage SPb-containing (or bacteriophage Z-containing) lysogens of Bacillus subtilis when growing on agar (but apparently not in broth cultures). Betacin inhibits the growth of non-lysogens but not that of lysogens containing SPb (or the related phage Z). [Book ref. 170, p. 280.] (cf. BACTERIOPHAGE fBA1.) Betacoccus Obsolete name for LEUCONOSTOC. Betadine See IODINE (a). Betaferon See INTERFERONS. Betaherpesvirinae (‘cytomegalovirus group’) A subfamily of viruses of the HERPESVIRIDAE (q.v.). The Betaherpesvirinae formerly consisted of only (i) the human cytomegalovirus group – type species human (beta) herpesvirus 5 (= human herpesvirus 5, HHV5; human cytomegalovirus, HCMV) and (ii) murine cytomegalovirus group – type species murid (beta) herpesvirus 1 (= murid herpesvirus 1; mouse cytomegalovirus, mouse CMV) [Book ref. 23, pp 49–50]; possible members included suid herpesvirus 2 (pig CMV, causal agent of INCLUSION BODY RHINITIS), murid herpesvirus 2 (rat CMV) and caviid herpesvirus 1 (guinea-pig CMV). Later, certain bovine herpesviruses were classified as ‘bovine cytomegaloviruses’ [JGV (1984) 65 697–706] (see also MALIGNANT CATARRHAL FEVER). Characteristically, the replication cycle of these viruses is appreciably longer than 24 hours (in contrast to the cycles 92

BIAcore of other herpesviruses). In culture they typically give rise to enlarged, rounded cells (cytomegalic cells) and slowly spreading foci of cell lysis. DNA-containing inclusion bodies may be seen in the nuclei and sometimes in the cytoplasm of infected cells. Typically, the host range for a given virus is narrow and is often restricted to a single species. Latent infection can be established in cell cultures and in vivo. HCMV (often truncated to CMV) is a large herpesvirus with a linear dsDNA genome of MWt ca. 1.5 × 108 containing terminal and internal repeated sequences; the genome encodes a number of structural and regulatory proteins. Each virion consists of the DNA–protein core, a capsid, and an external lipoprotein envelope bearing surface projections, the region between envelope and capsid (the ‘tegument’) containing several virus-encoded proteins. In the replication cycle of HCMV, the virion initially fuses with the cell membrane of the target cell, and the (unenveloped) virus migrates towards the nucleus. Viral DNA is replicated in the nucleus, and virus-encoded proteins are synthesized in the cytoplasm; the nucleocapsid is assembled in the nucleus. HCMV genes are transcribed in strict temporal sequence. The ‘immediate–early’ genes (expressed within 2–4 hours of infection) encode regulatory proteins that are needed for synthesis of ‘early’ and ‘late’ genes. The ‘early’ gene products include a DNA polymerase. ‘Late’ gene products include capsid proteins. Culture of human CMV is carried out in human fibroblasts. (See also SHELL VIAL ASSAY.) In vivo, replication appears to occur primarily in epithelial cells (e.g. in salivary glands, kidneys); HCMV is also known to infect peripheral blood leukocytes and haematopoietic progenitor cells. Infection with HCMV is endemic in human populations world-wide, but in most cases it is asymptomatic; primary infection may be followed by viral persistence which may take the form of low-level replication or latent infection. (The site of latency is currently unknown.) However, the virus is e.g. a common cause of congenital viral infections, and sometimes causes a disease resembling INFECTIOUS MONONUCLEOSIS. HCMV-mediated disease appears to occur most commonly among the immunocompromised (e.g. immunosuppressed transplant patients and AIDS patients) and in those with an immature immune system (e.g. neonates). Typically, HCMV-mediated disease is associated with conditions such as fever, hepatitis and leukopenia. (See also CYTOMEGALIC INCLUSION DISEASE.) [Epidemiology and transmission of HCMV: JID (1985) 152 243–248. Molecular biology and immunology of HCMV (review): Bioch. J. (1987) 241 313–324. Occupational risk of HCMV: RMM (1994) 5 33–38. HCMV in haematological disease: BCH (1995) 8 149–163.] The laboratory diagnosis of HCMV can be achieved in 65° C, and a minimum growth temperature >40° C [Sci. Prog. (1975) 62 373–393]. caldopentamine See POLYAMINES. calf diphtheria See NECROBACILLOSIS. calf pneumonia (enzootic pneumonia of calves; viral pneumonia of calves) A non-specific calf disease, the causal agent(s) being one or more viruses (e.g. adenoviruses, parainfluenza virus type 3, respiratory syncytial virus) frequently in association with bacteria (e.g. Chlamydia, Mycoplasma spp); typical symptoms: fever with constipation, followed by a mucopurulent nasal discharge, PNEUMONIA and diarrhoea. Poor hygiene and housing conditions (e.g. poor ventilation) and overcrowding appear to predispose towards the disease. Mortality rates can be high e.g. in acute RSV pneumonia. Control involves improvements in housing etc. and chemotherapy. (See also danofloxacin in entry QUINOLONE ANTIBIOTICS.) calf scours Scouring (see SCOURS) in young calves due to any of a range of microbial agents, e.g. enterotoxigenic strains of Escherichia coli, coronaviruses etc; aetiology may be complex (e.g. mixed bacterial and viral causal agents) and the occurrence and severity of the disease may involve both immunological and environmental factors. Calgitex See ALGINATE. Caliciales A heterogeneous order of (mostly LICHEN-forming) fungi of the ASCOMYCOTINA. Three families [Book ref. 64]: Caliciaceae. Mostly lichen-forming (photobiont: a green alga). Thallus thin crustose or immersed in the substratum (usually wood or bark). Apothecia (mazaedia) stalked or sessile. Lichenforming genera include e.g. Calicium, Chaenotheca, Coniocybe, Cyphelium. Mycocaliciaceae. Lichenicolous or fungicolous (possibly also lichen-forming) fungi in which the thallus is immersed in the substratum or absent. Apothecia stalked, asci thick-walled (mazaedia are not formed). Genera: e.g. Stenocybe. Sphaerophoraceae. All lichen-forming (photobiont: a green alga). Thallus foliose or fruticose. Apothecia (mazaedia) often globose, marginal or terminal. Genera: e.g. Sphaerophorus. Calicium See CALICIALES. Caliciviridae A family of VIRUSES which infect vertebrates; caliciviruses were formerly classified as a genus in the family Picornaviridae. The virions are non-enveloped, roughly spherical, ca. 35–39 nm diam., and have 32 characteristic cupshaped surface indentations – arranged with icosahedral symmetry – observable by electron microscopy of negatively stained preparations. The capsid contains a single major polypeptide species (MWt ca. 60000–71000) and a minor polypeptide (MWt ca. 15000). Genome: one molecule of positive-sense ssRNA (MWt ca. 2.6–2.8 × 106 ) which is apparently polyadenylated at the 3′ end but not capped at the 5′ end; the RNA is covalently linked (possibly at its 5′ end) to a protein (MWt ca. 10000–15000) which is necessary for infectivity. Replication occurs in the cytoplasm; dsRNAs (presumably replicative intermediates), genome-sized ssRNAs, and subgenomic ssRNAs can 118

CAMP test bacterial growth (apparently by withholding zinc ions), and this may antagonize certain antibiotics (e.g. b-lactams) used for chemotherapy. [Zinc in antimicrobial defence: RMM (1997) 8 217–224.] Calvatia See LYCOPERDALES. Calvin cycle (Calvin–Benson cycle, or Benson–Calvin–Bassham cycle; reductive pentose phosphate cycle; C3 cycle) A cyclic pathway used for the fixation of CARBON DIOXIDE by a wide range of AUTOTROPHS (q.v.). (See also METHYLOTROPHY.) The key enzymes in the Calvin cycle are RIBULOSE 1,5-BISPHOSPHATE CARBOXYLASE–OXYGENASE (RuBisCO), responsible for the CO2 fixing reaction, and phosphoribulokinase (ribulose 5-phosphate kinase, EC 2.7.1.19), responsible for regenerating the CO2 acceptor: ribulose 1,5-bisphosphate (RuBP). For every three molecules of CO2 fixed, six molecules of 3-phosphoglycerate are formed; of these, five are required for the regeneration of RuBP, while the remaining molecule is available as a source of carbon for biosynthesis (see figure on page 120). The ATP and reduced NAD(P) required to drive the cycle are supplied by the light reactions of PHOTOSYNTHESIS in phototrophs, or by the oxidation of reduced inorganic compounds in CHEMOLITHOAUTOTROPHS. [Regulation of the Calvin cycle in bacteria: AvL (1984) 50 473–487.] (See also PHOTORESPIRATION.) calyciform Cup-shaped. calymma See RADIOLARIA. Calymmatobacterium A genus (incertae sedis) of Gramnegative bacteria which occur as pathogens in man (see GRANULOMA INGUINALE). Cells: non-motile, pleomorphic, capsulated, round-ended rods, 0.5–1.5 × 1.0–2.0 µm. In exudates from diseased tissues the cells are usually seen in the cytoplasm of large mononuclear phagocytes. The organisms can be cultured in the chick embryo yolk sac or on specialized egg yolk-containing media. Optimum growth temperature: 37° C. Type (only) species: C. granulomatis. [Book ref. 22, pp. 585–587.] Calyptralegnia See SAPROLEGNIALES. CAM (1) Chorioallantoic membrane: see EMBRYONATED EGG. (2) CELL ADHESION MOLECULE. cam gene See METHANOGENESIS. CAM plasmid An IncP-2 Pseudomonas PLASMID (ca. 500 kb) which encodes the capacity for metabolization of camphor (compare TOL PLASMID). cAM373 See PHEROMONE. camalexin A PHYTOALEXIN (a substituted indole) produced by Arabidopsis. Camarops See SPHAERIALES. Camarosporium A genus of fungi of the class COELOMYCETES. (See also LEPTOSPHAERIA.) camelpox virus See ORTHOPOXVIRUS. Camembert cheese See CHEESE-MAKING. cAMP CYCLIC AMP. cAMP–CAP See CATABOLITE REPRESSION. CAMP factor See CAMP TEST. cAMP phosphodiesterase See ADENYLATE CYCLASE. cAMP receptor protein See CATABOLITE REPRESSION. CAMP test (Christie–Atkins–Munch-Petersen test) A test used for the presumptive identification of group B streptococci. (Some group A streptococci may also give a positive test, particularly under anaerobic conditions [Book ref. 46, pp. 1590–1591].) The organism under test is inoculated in a fine streak on the surface of ox- or sheep-blood agar; a second streak – perpendicular to the first but separated from it by a few millimetres – is made with a culture of a b-HAEMOLYSIN-producing strain of Staphylococcus aureus. The plate is then incubated (aerobically) for ca. 12 hours

be detected in infected cells. Mature viruses are released by host cell lysis. Caliciviruses are not sensitive to lipid solvents or to mild detergents, but are inactivated at pH 3–5. The family includes VESICULAR EXANTHEMA of swine virus (VESV), FELINE CALICIVIRUS (FCV) and SAN MIGUEL SEA LION VIRUS (SMSV); these three viruses are classified in the genus Calicivirus (type species: VESV serotype A). VESV, SMSV and FCV are readily propagated in cell culture and do not cause gastroenteritis (although they are pathogenic); morphologically similar viruses which have not been cultivated and which cause gastroenteritis in calves, piglets and humans (especially young children) are included as ‘possible members’ of the family [Book ref. 23, pp 133–134] (but see SMALL ROUND STRUCTURED VIRUSES). Calicivirus See CALICIVIRIDAE. California encephalitis (CE) An acute, usually mild, viral ENCEPHALITIS affecting mainly children below ca. 15 years of age; it occurs sporadically in forested areas in parts of North America. The CE virus (genus BUNYAVIRUS) occurs in small mammals and is transmitted by mosquitoes (mainly Aedes spp). California mastitis test (CMT; CM test) (vet.) A test, used for the indirect detection of MASTITIS, in which the number of white blood cells in milk is estimated. A reagent is added to the milk, causing a degree of gelation which corresponds to the white cell count; test results designated ‘negative’, ‘trace’, 1, 2 and 3 correspond to cell counts of ca. 60° C. In microbial mats from hot volcanic springs. [JGM (1983) 129 1149.] C. villosum. Isolated from subcutaneous abscesses in cats [IJSB (1979) 29 241–244]. C. welchii. See C. perfringens. Other species include e.g. C. aurantibutyricum, C. celatum, C. cellobioparum, C. coccoides, C. durum, C. fallax, C. felsineum, C. formicoaceticum, C. glycolicum, C. haemolyticum, C. indolis, C. lituseburense, C. oceanicum, C. putrefaciens, C. putrificum, and C. sticklandii. The genus Clostridium is heterogeneous, and proposals for rationalization have included the creation of a number of new genera (Caloramator, Filifactor, Moorella, Oxobacter and Oxalophagus) [IJSB (1994) 44 812–826]. clostripain A thiol PROTEASE (MWt ca. 50000; EC 3.4.22.8), obtained from Clostridium histolyticum, which acts specifically at basic amino acyl (arginyl, lysyl) residues. It also has amidase and esterase activity, cleaving amides and esters of amino acids. clot culture BLOOD CULTURE in which clotted blood, minus serum, is liquefied (e.g. with STREPTOKINASE) and the resulting fluid used as the inoculum. Apparently not widely used – due e.g. to the risk of contamination prior to the inoculation stage. clotrimazole (bis-phenyl-(2-chlorophenyl)-1-imidazole methane) One of the earliest of the clinically useful imidazole antifungal agents (see AZOLE ANTIFUNGAL AGENTS); it is used topically in the treatment of superficial mycoses (e.g. candidiasis, ringworm, pityriasis versicolor). clotting (of blood plasma) See FIBRIN; COAGULASE; ANTICOAGULANT. clover blackpatch disease See SLAFRAMINE. clover rot (clover sickness; sclerotinia crown and stem rot, SCSR) A disease of clover and other forage legumes caused by Sclerotinia spp (particularly S. trifoliorum). Leaves and petioles of infected plants turn olive-brown and subsequently rot; the disease progresses from the petioles to the stem and root, leading to the death of the plant. Control by repeated applications of e.g. benomyl or quintozene is effective but economically impracticable. [Review: Bot. Rev. (1984) 50 491–504.] clover wound tumour virus Syn. WOUND TUMOUR VIRUS. clover yellow mosaic virus See POTEXVIRUSES. clover yellows virus See CLOSTEROVIRUSES. cloverleaf structure (of tRNA) See TRNA. cloxacillin See PENICILLINS. club fungi See APHYLLOPHORALES (Clavariaceae). clubroot A disease of cruciferous plants (cabbages, cauliflowers, turnips etc) caused by Plasmodiophora brassicae (see PLASMODIOPHOROMYCETES). The roots of an infected plant become swollen and distorted, developing a single large gall (the ‘club’ symptom) or clusters of smaller galls (‘finger-and-toe disease’). The aerial parts of the plant may be stunted and may wilt in hot weather; the foliage often acquires a reddish tinge. Secondary infection of the galls by SOFT ROT bacteria commonly occurs. P. brassicae causes both hyperplasia and hypertrophy of infected tissues, apparently by inducing hyperauxiny (see AUXINS). Healthy plant tissue normally contains, in separate compartments, an indole compound, glucobrassicin, and an enzyme (glucosinolase) which hydrolyses glucobrassicin to indoleacetonitrile (IAN), a precursor of indoleacetic acid (IAA). P. brassicae apparently interferes with the compartmentalization of glucobrassicin and glucosinolase, resulting in increased levels of IAN (and hence IAA) in infected tissues. The cysts of P. brassicae can remain viable for years in the soil, and it is difficult to eradicate the disease from contaminated

land. Soil ‘sterilants’ such as dazomet may reduce the numbers of cysts. The disease can be controlled to some extent by dipping the roots of plants into a suspension of calomel, thiophanatemethyl or benomyl before planting. clue cells See BACTERIAL VAGINOSIS. clumping factor See COAGULASE. clumping-inducing agent See PHEROMONE. cluster cup See UREDINIOMYCETES stage I. cluster gene A gene encoding a multifunctional protein. (cf. GENE CLUSTER.) cluster of differentiation See CELL ADHESION MOLECULE. CLV Cassava latent virus (see GEMINIVIRUSES). cM CENTIMORGAN. CM COMPLETE MEDIUM. CM-cellulose (carboxymethylcellulose; CMC) A soluble derivative of CELLULOSE which is readily hydrolysed by most or all cellulolytic organisms. It is used e.g. to determine the ability of an organism or enzyme to degrade non-crystalline cellulose; endproduct formation or changes in the viscosity of CMC solutions may be measured. (cf. AVICEL; HE-CELLULOSE; FP-CELLULOSE.) CM test CALIFORNIA MASTITIS TEST. CMC (1) CM-CELLULOSE. (2) Chronic mucocutaneous CANDIDIASIS. CMI (1) CELL-MEDIATED IMMUNITY. (2) Commonwealth Mycological Institute, Kew, Surrey, UK. CML Chronic myelogenous leukaemia (see ABL). CMT CALIFORNIA MASTITIS TEST. CMV Cytomegalovirus (see BETAHERPESVIRINAE). CNA CALCIUM NUTRIENT AGAR. cnidosporans A group of protozoa formerly of the subphylum Cnidospora [JP (1964) 11 7–20], currently included in the phyla MICROSPORA and MYXOZOA. CNS (1) Central nervous system. (2) Coagulase-negative staphylococci. CO See CARBON MONOXIDE. 60 Co See IONIZING RADIATION. CO dehydrogenase A name used (confusingly) for (i) an enzyme which reduces carbon dioxide to carbon monoxide (see e.g. ACETOGENESIS), and (ii) an enzyme (cf. CO OXIDASE) which oxidizes carbon monoxide to carbon dioxide (see e.g. CARBOXYDOBACTERIA, METHANOGENESIS). CO dehydrogenase disulphide reductase See ACETOGENESIS. CO difference spectrum (of a cytochrome) The absorption spectrum of a given reduced, CARBON MONOXIDE-complexed CYTOCHROME minus the absorption spectrum of the same reduced, but non-complexed, cytochrome. CO oxidase (CO:acceptor oxidoreductase) An inducible enzyme which occurs in CARBOXYDOBACTERIA; it catalyses the oxidation of carbon monoxide to carbon dioxide in a reaction in which oxygen is derived from water rather than from air: CO + H2 O −−→ CO2 + 2H+ + 2e− In at least some carboxydobacteria the enzyme contains a noncovalently bound molybdenopterin moiety. [Properties of CO oxidases: MS (1986) 3 149–153.] CO2 See CARBON DIOXIDE. CO2 -stat See CONTINUOUS CULTURE. CoA COENZYME A. coa gene See STAPHYLOCOCCUS (S. aureus). Coactin Syn. MECILLINAM. co-activator See OPERON. co-agglutination (1) See PROTEIN A. (2) Joint agglutination (analogous to CO-PRECIPITATION). (3) Agglutination of different strains 174

cobra venom factor or species of microorganism by a given antiserum (see e.g. WEIL–FELIX TEST). coaggregation Cell-to-cell adhesion in which the cells of one species adhere more or less specifically to those of a different species; e.g. Actinomyces viscosus and Streptococcus sanguis coaggregate by LECTIN –carbohydrate interaction [JGM (1984) 130 1351–1357]. coagulase Any bacterial component or product which causes coagulation (clotting) or PARACOAGULATION in PLASMA containing an anticoagulant such as citrate, heparin or oxalate. Coagulases are produced e.g. by certain staphylococci and by Yersinia pestis. Staphylococci produce two structurally and functionally distinct types of coagulase: free coagulase (staphylocoagulase, a protein which is released into the medium) and bound coagulase (clumping factor, a protein component of the cell wall). Staphylocoagulase causes a true clotting of plasma (from certain species only); it interacts with a ‘coagulase reacting factor’, CRF, in the plasma (believed to be prothrombin or a form of it) to form a complex (‘staphylothrombin’) which acts on plasma fibrinogen, converting it into insoluble fibrin – apparently by limited proteolytic action similar or identical to that of normal thrombin. The resulting clot differs from a normal clot in that e.g. it is not stabilized by Factor XIII (a normal blood-clotting factor) and it is much more resistant to fibrinolysin than is a normal clot. Several antigenically distinct staphylocoagulases are produced by different staphylococcal strains. The property of staphylocoagulase production is often used to distinguish between pathogenic and non-pathogenic strains, since there is a high degree of correlation between staphylocoagulase production and virulence (although coagulase-negative staphylococci are not necessarily harmless). However, although it can apparently exert its effect freely in vivo, the role of staphylocoagulase – if any – in pathogenesis is unknown. In vitro, the activity of staphylocoagulase is inhibited by various chemicals, particularly oxidizing agents, and by certain antibiotics (e.g. some penicillins). Staphylococcal clumping factor does not form a true clot in plasma; rather, it induces clumping of the cells (paracoagulation) in the presence of fibrinogen. When mixed with plasma, cells with clumping factor bind fibrinogen near the Cterminal ends of its g-chains – this apparently being responsible for the clumping of the cells [Biochem. (1982) 21 1407–1413, 1414–1420]. The role of clumping factor in pathogenesis (if any) is unknown. (cf. CCFAS.) [Isolation of clumping factor from S. aureus: Inf. Immun. (1985) 49 700–708.] Staphylocoagulase and clumping factor may be detected by different forms of the COAGULASE TEST. [Review of staphylococcal coagulases: Book ref. 44, pp. 525–557.] coagulase test Any procedure used to determine whether or not a given bacterial strain produces a COAGULASE. The tests described below are used for staphylococci. The tube test (which detects staphylocoagulase) simply involves incubating the test organism with a suitable plasma sample. In one of many methods, 0.5–1.0 ml of plasma is mixed with an equal (or smaller) volume of an 18–24-hour broth culture of the organism, and the tube is incubated at 35–37° C; the tube is examined at hourly intervals, and after overnight incubation, for clot formation – a firm clot which does not move when the tube is shaken being regarded as a positive result [Book ref. 44, pp. 526–527]. Known coagulase-positive and coagulasenegative strains should be used as controls. Plasma containing anticoagulants such as citrate, oxalate, EDTA, or heparin may be used, although heparin has been reported to delay clot formation;

any organism tested for coagulase formation should be unable to metabolize the anticoagulant: citrated plasma, for example, may be clotted by coagulase-negative citrate-utilizing bacteria. Preservatives (e.g. thiomersal) may inhibit staphylocoagulase. Purified fibrinogen, or freeze-dried plasma, may be used instead of fresh plasma. Staphylocoagulases from strains pathogenic for man exhibit maximum activity in human or rabbit plasma. Strains which produce large amounts of fibrinolytic enzymes (see FIBRINOLYSIS) may not form clots, or may lyse any clot formed; such strains are more commonly found among isolates from human infections than among isolates from animals. (See also PSEUDOCOAGULASE.) The slide test detects clumping factor (see COAGULASE). A thick, saline suspension is prepared (on a slide) from a colony of the test strain grown on a non-selective medium; a loopful of citrated or oxalated human or rabbit plasma (not sheep or guineapig plasma) is stirred into the suspension. (Fibrinogen may be used instead of plasma e.g. to avoid any antibody-mediated agglutination of the bacteria.) Clumping of cells within ca. 5 sec indicates the presence of clumping factor. (A false-negative result may be obtained with capsulated strains [Book ref. 44, p. 505].) Controls should be used (cf. AUTO-AGGLUTINATION). (See also STAPHYLOSLIDE.) There is a high, though not total, correlation between positive results in the tube and slide tests; however, a positive slide test should not be regarded as evidence of staphylocoagulase production. A plate method may be used to detect staphylocoagulasepositive organisms. The test organism is inoculated onto the surface of an agar growth medium containing citrated plasma or purified fibrinogen and prothrombin. After overnight incubation, coagulase-positive colonies are each surrounded by a dense zone of precipitated fibrin. This method is useful for estimating numbers of coagulase-positive staphylococci in e.g. foods, but is too slow and prone to misleading results for use in routine clinical diagnosis. coal biodegradation Certain fungi are capable of growing on coal – particularly lignite (‘brown coal’, a form which is relatively low in carbon and rich in volatile compounds) – as the sole source of nutrients; such fungi include e.g. the basidiomycetes Polyporus versicolor and Poria monticola [AEM (1982) 44 23–27] and various other species (e.g. Aspergillus terreus and species of Candida, Mucor, Paecilomyces and Penicillium [SAAM (1985) 6 236–238]). Growth generally appears to be restricted to the surface of the coal; the nature of the substrates utilized is unknown. Coal products, such as benzene and toluene (derived from coal tar), may be degraded e.g. by combinations of bacteria [Nature (1998) 396 730]. [Aerobic and anaerobic degradation of toluene by Thauera: AEM (2004) 70 1385–1392.] (See also LEACHING.) CoASH (CoA-SH) Uncombined COENZYME A. coated lens See BLOOMED LENS. coated pit See PINOCYTOSIS. coated vesicle See PINOCYTOSIS. cobalamin See VITAMIN B12 . cobamide coenzymes See VITAMIN B12 . cobinamide See VITAMIN B12 . cobra venom factor (CVF) Either of the two proteins, derived from cobra venom, which affect the alternative pathway of COMPLEMENT FIXATION. CVFs mimic C3b. CVF from Naja naja binds Factor B and promotes its cleavage (by Factor D) to form a C3 convertase; it can also give rise to a C5 convertase. CVF 175

cobweb disease from Naja haje can also give rise to a C3 convertase but not to a C5 convertase. Unlike C3b, CVF is not inactivated by Factors I and H; it therefore forms a C3 convertase which is not subject to regulation. cobweb disease A MUSHROOM DISEASE caused by Hypomyces rosellus; it can be controlled e.g. by BENOMYL or PROCHLORAZ [PP (1983) 32 123–131]. cocarboxylase See THIAMINE. coccal Pertaining to a COCCUS. cocci See COCCUS. coccidia The common name for protozoa of the suborder EIMERIORINA. Coccidia (1) A subclass of protozoa (class Telosporea) later incorporated, with the TOXOPLASMEA, in the subclass COCCIDIASINA. (2) A subclass of protozoa (class Sporozoea [JP (1980) 27 37–58]) equivalent to the COCCIDIASINA. Coccidiascus A genus of yeasts (family METSCHNIKOWIACEAE). Cells: spherical to ovoid (5–15 µm diam./length), with a large vacuole and nucleus; neither pseudomycelium nor mycelium is formed. C. legeri (sole species) occurs as a parasite in intestinal epithelial cells of Drosophila spp; it has not been cultured in vitro. [Book ref. 100, pp. 123–124.] Coccidiasina A subclass of protozoa (class SPOROZOASIDA) parasitic mainly in vertebrates but also in invertebrates. In members of this subclass the mature gametocytes typically occur intracellularly in the host (cf. GREGARINASINA). Orders: Agamococcidiorida, EUCOCCIDIORIDA, Protococcidiorida. coccidiasis Any subclinical or very mild infection with a coccidian parasite – as distinct from clinical COCCIDIOSIS. Coccidioides A genus of fungi (class HYPHOMYCETES); C. immitis is a saprotroph in desert soils in hot, arid regions of the American continent, and is the causal agent of COCCIDIOIDOMYCOSIS. In mammalian tissues it occurs mainly as multinucleate, thickwalled, spherical (ca. 20–80 µm) cells (spherules or sporangia). The spherule protoplasm divides into multinucleate protospores and then into uninucleate sporangiospores (endospores) which are released on rupture of the spherule wall and develop into new spherules. C. immitis grows readily on various types of media, forming a mycelium which fragments into barrelshaped arthroconidia which are highly infective and very easily dispersed by air currents. coccidioidin Any antigenic preparation derived from Coccidioides immitis and used in a diagnostic SKIN TEST for COCCIDIOIDOMYCOSIS. coccidioidomycosis (San Joaquin Valley fever; desert fever) A disease of man and animals caused by Coccidioides immitis; it occurs in hot, arid regions of the American continent. Infection usually occurs by inhalation of wind-borne spores (especially arthroconidia); person-to-person transmission does not occur. Infection may be asymptomatic or may result in an acute, self-limiting respiratory disease resembling a common cold or influenza – often with severe chest pain. Rarely, mycetomas (‘fungus balls’) may develop in the lungs. Less common symptoms include joint pains (‘desert rheumatism’) and/or skin lesions. The primary infection occasionally leads to progressive, often fatal, disseminated disease (coccidioidal granuloma) with lesions in e.g. skin, joints, meninges. Lab. diagnosis: serological tests; SKIN TESTS using COCCIDIOIDIN or SPHERULIN; demonstration of the fungus by histology, culture and/or animal inoculation. Treatment: ketoconazole, amphotericin B. [Book ref. 25.] coccidiosis Any disease of man and other animals caused by protozoa of the suborder EIMERIORINA. Coccidioses are typically contracted via the oral route and may involve the intestinal

tract and/or various other tissues; they may be mild to fatal. Coccidioses of domestic animals and poultry are often of economic importance. (a) Poultry. In chickens, Eimeria necatrix causes severe haemorrhage in the small intestine, and E. tenella causes haemorrhage and necrosis in the caecum; other pathogens include e.g. E. acervulina and E. brunetti. In ducks, Tyzzeria perniciosa causes haemorrhagic intestinal disease. In turkeys, severe inflammation of the intestine is caused by e.g. E. adenoeides and E. meleagrimitis. (b) Domestic animals. In cattle, haemorrhagic lesions in the intestine are caused e.g. by E. bovis and E. z¨urnii (E. zuernii ); an increased incidence of disease may occur during cold weather (‘winter coccidiosis’). In sheep, intestinal disease may be caused e.g. by E. ahsata, E. ovina or E. ovinoidalis. In pigs, enteritis, severe diarrhoea and emaciation are caused e.g. by E. scabra. In rabbits, intestinal disease (often fatal) is caused e.g. by E. magna and E. irresidua; E. stiedae (E. stiedai) causes diarrhoea, enlargement of the liver and bile ducts, and emaciation. In cats, intestinal symptoms may be due to infection by Isospora spp (which may also infect dogs) or Toxoplasma (see TOXOPLASMOSIS). (cf. SARCOSPORIDIOSIS; see also EQUINE PROTOZOAL MYELOENCEPHALITIS.) (c) Man. Infections involving Isospora belli and I. hominis are believed to be commonly asymptomatic, but intestinal symptoms may occur. (See also CRYPTOSPORIDIOSIS, SARCOSPORIDIOSIS and TOXOPLASMOSIS.) Diagnosis of animal coccidioses involves e.g. SPORULATION of oocysts concentrated from fresh faeces. [Identification of Eimeria spp: Book ref. 7, pp. 7–30. Identification of coccidia: Book ref. 18, pp. 80–91. Coccidian pathogenicity: Book ref. 18, pp. 287–327. Pathology, lab. diagnosis, and therapy in cryptosporidiosis, isosporiasis, sarcosporidiosis and toxoplasmosis: Book ref. 118, pp. 211–236.] coccidium An individual, or a particular strain, of an organism of the suborder EIMERIORINA. coccobacillus A bacterial cell intermediate in morphology between a COCCUS and a BACILLUS. Coccodiscus See RADIOLARIA. coccoid More or less spherical: cf. COCCUS. coccoid bodies Thin-walled coccoid forms which develop from the helical or vibrioid cells in old cultures of e.g. Aquaspirillum, Campylobacter and Oceanospirillum spp; their formation is enhanced by treatment with mitomycin or UV light. Coccoid bodies resemble sphaeroplasts but are resistant to osmotic lysis; the majority are apparently viable, ‘germinating’ to form normal cells when transferred to a fresh medium. (cf. MICROCYST.) coccolith A calcified scale, generally measuring a few micrometres or less in diam., present on the cell surface in certain cells of the COCCOLITHOPHORIDS. Coccoliths contain crystals of calcite – either of a single type (in holococcolithis) or, more commonly, of different shapes and sizes (in heterococcoliths); coccoliths are often elliptical in shape (but may be round, polygonal, etc) and they commonly exhibit intricate patterns and ornamentations which are species-specific. The coccoliths of present-day coccolithophorids form a significant proportion of some deep-sea oozes; however, coccolithophorids were even more abundant in previous geological ages, particularly in the Cretaceous, and the coccoliths of these organisms are major constituents of Mesozoic (Jurassic and Cretaceous) and Cenozoic chalks and marls. Coccolith morphology apparently changed rapidly over the ages, making fossil coccoliths useful markers in the biostratigraphy of sedimentary rocks [Book ref. 136, 176

codon bias pp. 329–426 (Mesozoic coccoliths), pp. 427–554 (Cenozoic coccoliths)]. (See also FORAMINIFERIDA.) coccolithophorids Those algae of the PRYMNESIOPHYCEAE in which the cell bears a covering of one to several layers of COCCOLITHS during at least some stage of the life cycle. For example, Emiliana huxleyi – the commonest living coccolithophorid – has a life cycle in which two distinct types of cell are formed: the motile ‘S cell’, which is biflagellated and covered with one or several layers of organic scales, and the non-motile ‘C cell’, which lacks flagella and organic scales but is enclosed by a shell-like coccosphere consisting of one or several layers of coccoliths. Life cycles involving motile and non-motile phases also occur in other genera (e.g. Coccolithus, Cricosphaera, Hymenomonas). Coccolithophorids are planktonic marine organisms which are particularly common in tropical waters. Coccolithus See COCCOLITHOPHORIDS. Coccomyces See RHYTISMATALES. Coccomyxa A genus of unicellular, non-motile green algae (division CHLOROPHYTA) which occur as photobionts in certain lichens (see e.g. NEPHROMA, PELTIGERA, SOLORINA). The cells are small, ovoid, and contain a single parietal chloroplast with no pyrenoid; flagellated stages and sexual reproduction have never been observed. (See also RIBITOL and SPOROPOLLENIN.) Cocconeis See DIATOMS. coccosphere See COCCOLITHOPHORIDS. coccus (pl. cocci) A spherical (or near-spherical) bacterial cell. According to species, cocci may occur singly, in pairs (see DIPLOCOCCUS), in regular groups of four or more (see TETRAD and PACKET), in chains, or in irregular clusters. (cf. BACILLUS sense 2.) Cochliobolus See DOTHIDEALES. Cochliopodium A genus of amoebae (order ARCELLINIDA) which have a type of test known as a tectum: a more or less flexible, closely adherent covering of small scales (distinguishable only by electron microscopy); in some species the scales bear spines which may be visible by light microscopy, while in others sand grains and other debris may adhere to the scales. Species occur in fresh water, activated sludge, etc. [Book ref. 133, pp. 76–82.] Cochlonema See ZOOPAGALES. cocksfoot mottle virus See SOBEMOVIRUSES. cocksfoot streak virus See POTYVIRUSES. cocoa Cocoa and chocolate are made from the seeds (beans) of the cacao plant Theobroma cacao. The cacao fruit is a pod containing up to 50 beans covered by a white mucilage. After harvesting, the pods are opened and the beans are extracted, piled up (e.g. in perforated boxes or on plantain leaves) and covered (e.g. with leaves). A fermentation then occurs: initially, various yeasts carry out an ALCOHOLIC FERMENTATION, and this is rapidly followed by ACETIFICATION by acetic acid bacteria – the production of acetic acid and heat inhibiting further yeast action. Other bacteria (e.g. lactic acid bacteria) and moulds are also present. During the process, which lasts ca. 6 days, the beans darken in colour (owing to oxidation) and the mucilage gradually disappears. The beans are then dried. The characteristic cocoa flavour develops only after the beans are roasted. [Book ref. 5, pp. 275–292.] (cf. COFFEE; see also CACAO DISEASES.) cocoa necrosis virus See NEPOVIRUSES. coconut cadang-cadang viroid (CCCV) A VIROID which infects coconut palms; infected palms may be killed, and the viroid has caused severe economic losses e.g. in the Philippines (cf. TINANGAJA DISEASE). The natural mode of transmission is unknown. CCCV is unique among known viroids in that it exists

as four different RNA species. Two RNAs – designated RNA1 small or RNA-1 fast (246 nucleotides) and RNA-2 small or RNA-2 fast (492 nucleotides) – occur in infected palms during the early stages of cadang-cadang disease; later, two additional RNAs – RNA-1 large or RNA-1 slow (287 nucleotides) and RNA-2 large or RNA-2 slow (574 nucleotides) – appear and eventually predominate. The RNA-1 small is regarded as the unit CCCV RNA; the other three RNAs are apparently derived from RNA-1 small by sequence duplication. [Nature (1982) 299 316–321.] coconut hartrot See HARTROT. coconut lethal yellowing A YELLOWS disease of the coconut palm caused by an MLO. The disease is controlled, commercially, by the use of oxytetracycline hydrochloride. coconut palm rhinoceros beetle (biological control) See BACULOVIRIDAE. co-conversion (mol. biol.) See RECOMBINATION. codecarboxylase See PYRIDOXINE. coding strand A term which (like non-coding strand) is frequently used with opposite meanings by different authors. Originally, the term was generally used to refer to that strand of a gene which acts as the template on which mRNA is synthesized during transcription – the strand whose sequence is complementary to that of mRNA. Currently, there appears to be a consensus for the opposite meaning, i.e. that strand of a gene which is not transcribed (i.e. not used as a template) and whose sequence is homologous to that of mRNA. (Even so, given the confusion present in the literature, it may be wise to define the term, in relation to mRNA, whenever it is used.) The coding strand is also called the sense strand or the plus (+) strand. The non-coding strand of a gene (which is complementary to the coding strand) is thus the template strand; it is also called the antisense strand or the minus strand. Interestingly, a certain gene in the fruitfly (Drosophila) has been shown to contain protein-encoding information in both of the strands [Nature (2001) 409 1000]. Codium A genus of siphonaceous green seaweeds (division CHLOROPHYTA). The thallus is terete and dichotomously branched; it is composed of a colourless central medulla of interwoven filaments from which arises a surrounding layer of inflated green branchlets (‘utricles’). Anisogametes are produced in the utricles; these are initially non-motile, later becoming biflagellate. (See also CELL WALL; ELYSIA; NITROGEN FIXATION.) codominant gene One of two (or more) genes which, when present together, specify a phenotype unlike that specified by either (or any) of the genes individually. codon See GENETIC CODE. codon bias In the expression of a heterologous (i.e. ‘foreign’) gene (e.g. a mammalian gene in Escherichia coli): inefficient translation due to the presence of certain codon(s) for which the host cell has insufficient numbers of the corresponding tRNA(s); codon bias can be a problem e.g. when high-level expression in E. coli is required from a heterologous gene containing a high frequency of codons such as the proline codon CCC and/or the arginine codon AGG – codons which occur rarely in homologous (E. coli ) genes. Attempts at high-level expression of genes containing relatively high frequencies of codons that are ‘rare’ for the host cell may lead e.g. to slowing or termination of translation and the degradation of mRNA. One solution to the problem is to insert into the host cell extra (plasmid-borne) copies of the relevant tRNA-encoding gene(s). Codon bias may also arise as a result of a same-sense mutation which replaces a common or ‘routine’ codon with a synonymous but infrequent codon (see SILENT MUTATION). 177

Codonella for catalysis of redox reactions. (2) Any low-MWt, nonprotein organic molecule – whether freely dissociable or firmly bound – necessary for the activity of a given enzyme. coenzyme F420 See METHANOGENESIS. coenzyme F430 See METHANOGENESIS. coenzyme I NAD (q.v.). coenzyme II NADP: see NAD. coenzyme A (CoA) A coenzyme, derived from PANTOTHENIC ACID (see figure), which functions as a carrier of acyl groups – with which it forms thioesters (CoA.S.CO.R). (Uncombined coenzyme A may be represented as CoA-SH or CoASH.) Acylcoenzyme A thioesters have a high free energy of hydrolysis and are commonly involved in SUBSTRATE-LEVEL PHOSPHORYLATIONS. coenzyme B See METHANOGENESIS. coenzyme B12 See VITAMIN B12 coenzyme F See FOLIC ACID. coenzyme M See METHANOGENESIS. coenzyme Q See QUINONES. coenzyme R Syn. BIOTIN. cofactor (1) Any low-MWt, non-protein (organic or inorganic) factor which is necessary for the activity of a given enzyme (cf. COENZYME; PROSTHETIC GROUP). (2) (Syn. activator) Any inorganic component (e.g. metal ion) necessary for the activity of a given enzyme. (3) Any organic or inorganic factor necessary for the activity of an enzyme or enzyme complex. coffee The commercial preparation of coffee from ripe coffee fruits (‘cherries’) requires the removal of the sticky mucilaginous mesocarp which surrounds the two beans in each fruit. This may be achieved mechanically or chemically, but the preferred method is by fermentation – which also improves the quality and appearance of the beans. The coffee fruits are pulped to disrupt the skins and then allowed to ferment either under water or ‘dry’. The mucilage is degraded both by enzymes in the fruit itself and by microbial extracellular enzymes. (Commercial preparations of mould enzymes have also been used.) Various bacteria, yeasts and moulds are associated with the fermenting coffee, the most important probably being pectinolytic species of e.g. Bacillus, Erwinia, Aspergillus, Fusarium and Penicillium. After the fermentation, the beans are washed, dried, blended, roasted and ground before use. (cf. COCOA.) coffee berry disease A disease of the coffee plant characterized by sunken, anthracnose lesions on the berries; causal agent: Colletotrichum coffeanum. [Review: Phytopathol. Paper number 20, March 1977.]

Codonella See TINTINNINA. Codonosiga See CHOANOFLAGELLIDA. Coe virus Coxsackievirus A21: see ENTEROVIRUS. coelichelin A tripeptide SIDEROPHORE, encoded by Streptomyces coelicolor, which is synthesized by a non-ribosomal synthetase [see e.g. FEMS (2000) 187 111–114]. Coelomomyces See BLASTOCLADIALES. Coelomycetes A class of fungi (subdivision DEUTEROMYCOTINA) which form septate mycelium and in which the conidiophores line a discrete saucer-shaped, cupulate, flask-shaped or loculate conidioma – e.g. an ACERVULUS or a PYCNIDIUM. (cf. HYPHOMYCETES.) Orders [Book ref. 64, pp. 87–88]: MELANCONIALES, PYCNOTHYRIALES and SPHAEROPSIDALES. Coeloseira See RHODOPHYTA. Coelosphaerium A phycological genus of unicellular ‘bluegreen algae’ (Chroococcaceae) in which the cells occur in a single layer at the periphery of a spherical colony; the cells are ellipsoidal, divide longitudinally, and contain GAS VACUOLES. The organisms are planktonic e.g. in freshwater lakes. (See CYANOBACTERIA.) coelozoic Refers to a parasite which lives within its host in body fluids – e.g. in the gall bladder, bloodstream (outside blood cells), urinary tract, etc. (cf. HISTOZOIC.) Coemansia See KICKXELLALES. coenobium (1) (bacteriol.) A MICROCOLONY (sense 1) in which, following cell division, the cells of a clone form a regular array. Thus, e.g. Thiopedia typically forms a coenobium which consists of a flat sheet of 16 contiguous cells in a ‘4 × 4’ arrangement – but coenobia containing up to ca. 64 cells may be formed. In Brachyarcus the coenobia consist of symmetrically arranged cells embedded in a matrix. (2) (algol.) In certain types of algae: a colonial form which consists of a number of cells arranged in a specific way; the number of cells in a coenobium is usually a stable feature of a given species or genus. Coenobia are formed e.g. by Scenedesmus and Volvox. coenocyte (microbiol.) A multinucleate cell, structure, or organism, formed by the division of an existing multinucleate entity or by nuclear division without the formation of dividing walls or septa. (cf. SYNCYTIUM.) Coenocytes occur e.g. in SIPHONACEOUS and SIPHONOCLADOUS algae; the hyphae of many fungi may be regarded as coenocytic. coenzyme (1) Any low-MWt, non-protein, freely dissociable organic molecule which is necessary for the activity of a given enzyme (cf. PROSTHETIC GROUP); e.g., dehydrogenases require electron acceptors such as NAD+ or NADP+ NH2 N

N

O N

5′

N

CH2

O 1′

H

H

4′

H

OH

O

P O

O −

O

−

O

O

CH2

C

C

O

H

C

N

CH2

CH2

O

H

C

N

CH2

CH2

SH

CH3 H

pantothenic acid

O −

CH3 OH

P

H

3′

2′

O

P O −

O

adenosine 3′,5′-bisphosphate

pantetheine 4′-phosphate

COENZYME A (CoA-SH)

178

2-mercaptoethylamine (= cysteamine)

cold-shock response colchicine An alkaloid found e.g. in the meadow saffron (Colchicum autumnale); the colchicine molecule consists of a tricyclic skeleton which includes an aromatic ring (substituted with three methoxy groups) and a tropolone ring. At low concentrations colchicine can e.g. bind to TUBULIN and prevent the in vitro or in vivo assembly of tubulin into MICROTUBULES; colchicine can thus e.g. inhibit MITOSIS in mammalian, plant, and other cells. (However, some complex microtubular structures – e.g. CENTRIOLES, and the ciliar and flagellar axonemes – are normally resistant to colchicine.) The in vitro effect of colchicine on microtubule assembly can be abolished e.g. by ultraviolet radiation (which converts colchicine to lumicolchicine).

coffee diseases For diseases of the coffee plant (Coffea spp) see e.g. COFFEE BERRY DISEASE, COFFEE RUST, FUSARIUM WILT, PHLOEM NECROSIS, RED RUST. coffee ringspot virus See RHABDOVIRIDAE. coffee rust A COFFEE DISEASE caused by Hemileia vastatrix. Yellowish spots, which become orange, appear on the undersides of the leaves, corresponding dark patches appearing on the upper surfaces; infected leaves are shed, and yields of berries are greatly reduced. cognac See SPIRITS. cognate In (e.g.) immunology, a word commonly used to mean ‘corresponding’ or ‘matching’. cognate help (linked recognition) (immunol.) The binding of a helper T cell to an antigen which is also bound by a B cell; the B and T cells are thus physically linked via the antigen. Such joint binding of antigen is accompanied by contact between various receptors and ligands on the two cells; this leads to activation and proliferation of both types of cell and formation of antibodies by the B cell. (See also ANTIBODY FORMATION.) The determinant (epitope) bound by the B cell is sometimes referred to as the ‘hapten’, that bound by the T cell as the ‘carrier’ – terminology that derives from earlier hapten–carrier studies. cohesive ends Syn. STICKY ENDS. cointegrate The (circular) product of fusion between two circular replicons (e.g. two plasmids, or a plasmid and a bacterial chromosome) mediated by a TRANSPOSABLE ELEMENT (TE). Cointegration may occur as a result of a transposition event between a replicon containing a TE and one containing a target sequence for that TE. The transposition is accompanied by duplication of both the TE and a sequence at the target site: see entry TRANSPOSABLE ELEMENT. An alternative mechanism of cointegrate formation involves recA-dependent reciprocal recombination between homologous TEs in each of two replicons. (Some authors reserve the term ‘cointegration’ for the transposition event only.) (See also Tn3.) (The term ‘cointegrate’ has also been used for any product of fusion between two replicons, regardless of the mechanism by which fusion occurred.) coital exanthema See EQUINE COITAL EXANTHEMA. col factor See COLICIN PLASMID. col plasmid See COLICIN PLASMID. Colacium A genus of EUGLENOID FLAGELLATES. The organisms differ from other euglenids in that they generally form dendroid or palmelloid colonies; flagellated cells, when formed, resemble those of EUGLENA. C. libellae overwinters in association with damselfly nymphs, becoming established in the rectum of the insect. colanic acid A capsular heteropolysaccharide (the ‘M antigen’) produced e.g. by strains of Escherichia coli and Salmonella. K12 strains of E. coli produce colanic acid and form mucoid colonies at 30° C but not at 37° C; certain mutants (lon or capR) produce colanic acid and appear mucoid at 37° C. Colanic acid consists of repeating trisaccharide units of (-glucose-fucose-fucose-), the central fucose residue of each unit carrying a trisaccharide branch (galactose-glucuronic acidgalactose-). Non-carbohydrate substituents (e.g. acetyl and pyruvyl groups) may be present, the nature and position of such groups varying e.g. with strain. [Organization of the E. coli K12 gene cluster responsible for production of colanic acid: JB (1996) 178 4885–4893.] Colcemid (trade name) DEMECOLCINE.

CH3O NHCOCH3 CH3O CH3O O OCH3

COLCHICINE

cold See COMMON COLD. cold abscess See ABSCESS. cold agglutinins Agglutinins which combine maximally with homologous or cross-reacting antigens at low temperatures (e.g. 4° C) but not at e.g. 37° C. Cold agglutinins may be detectable e.g. in the serum of patients suffering from PRIMARY ATYPICAL PNEUMONIA (sense 2), and they can be assayed by their ability to agglutinate human group O RBCs. Cold agglutinins occur also in certain other diseases – e.g. pneumonia caused by adenoviruses. cold enrichment ENRICHMENT of psychrophilic or psychrotrophic organisms by incubation at low temperatures (see e.g. Yersinia enterocolitica). ColD plasmid See COLICIN D and COLICIN PLASMID. cold shock See OSMOTIC SHOCK. cold-shock response In prokaryotes and eukaryotes: an apparently adaptive response to a down-shift in temperature (e.g. 37 → 10° C or, in general, a down-shift of at least 13° C) characterized by (i) initial cessation of growth, with resumption after a lag period; (ii) induction or increased synthesis of cold-shock proteins; (iii) repression of heat-shock proteins; (iv) generalized inhibition of protein synthesis, but ongoing synthesis of certain proteins involved in transcription and translation. In Escherichia coli, the cold-shock proteins include CspA, RecA, IF-2 (initiation factor 2, which mediates binding of Nformylmethionine-charged tRNA to the 30S ribosomal subunit), NusA (involved in the last stage of transcription), and the asubunit of DNA gyrase. So far, no cold-inducible sigma factor has been identified. CspA is a small (70 amino-acid) protein which is inducible immediately (at the level of transcription) on temperature downshift. It appears to interact with nucleic acids. Suggested functions of CspA include: (i) a low-temperature activator of translation; (ii) an ‘RNA chaperone’ that inhibits secondary structures in RNA and which may be important e.g. for efficient translation of mRNA at low temperatures [JBC (1997) 272 196–202]; (iii) an agent which inhibits translation from specific mRNAs. (It has been reported that CspA is normally produced 179

cold sore during early exponential growth at 37° C in E. coli – i.e. under non-stress conditions [EMBO (1999) 18 1653–1659].) The cold-shock response can also be triggered by certain inhibitors of translation – for example, the antibiotics chloramphenicol, erythromycin and tetracycline; this has suggested that a decrease in translational capacity may be an important factor in the induction of the cold-shock response [Mol. Microbiol. (1994) 11 811–818]. cold sore (fever blister) (1) The lesion associated with labial herpes (see HERPES SIMPLEX). (2) The recurrent thin-walled vesicular mucocutaneous lesion associated with any of the various forms of HERPES SIMPLEX. cold stability factor See MICROTUBULE-ASSOCIATED PROTEINS. cold water disease (peduncle disease; low temperature disease) A FISH DISEASE affecting young salmonids below 10° C. The tail and peduncle undergo slow progressive necrosis. Causal agent: Flexibacter psychrophila (‘Cytophaga psychrophila’). ColE1 plasmid A small (MWt ca. 4.2 × 106 ), non-conjugative, ccc dsDNA COLICIN PLASMID which is normally maintained in the host cell at a copy number of ca. 10–30. In ColE1, DNA REPLICATION occurs by the CAIRNS MECHANISM. Replication is initiated from a fixed origin and (in contrast to chromosomal replication in Escherichia coli ) proceeds unidirectionally from the origin; it is not dependent on plasmid-encoded proteins but requires the cell’s RNA polymerase, DNA polymerases I and III and components of the PRIMOSOME. The first several hundred nucleotides of the leading strand are synthesized by DNA polymerase I from an RNA primer synthesized by RNA polymerase; subsequent DNA chain elongation is carried out by DNA polymerase III. Initiation of plasmid replication is regulated at the level of primer formation. During the initiation process, two RNA transcripts are synthesized, one on each DNA strand, at the same region ca. 500 nt upstream from the origin (ori). The transcript on the H strand (RNA II) can – unless prevented (see later) – extend to the origin and give rise to a primer for synthesis of the leading strand; the transcript on the L strand (RNA I, 108 nt long) is complementary to the 5′ terminal region of RNA II and behaves as a trans-acting repressor of plasmid replication. According to a current model, the 5′ end of RNA II is synthesized as a free (single-stranded) transcript, but as the RNA polymerase approaches ori the transcript and template form a DNA/RNA hybrid; the RNA strand in this hybrid is cleaved by RNASE H to form a free hydroxyl (−OH) terminal suitable for extension by DNA polymerase, i.e. the cleaved end of the RNA transcript, at ori, functions as a primer. (Although RNase H is essential for replication of ColE1 in vitro, its role in vivo has been questioned [JB (1986) 166 143–147].) Whether or not a functional primer is formed from the RNA II transcript, as described above, is influenced by several factors – factors which, by regulating the initiation of replication, determine the COPY NUMBER of the plasmid. One regulatory factor is RNA I. RNA I and RNA II each form several stem-and-loop structures which, because the two transcripts are complementary, can undergo mutual base-pairing; when this happens, it inhibits development of a functional primer at the RNA/DNA hybrid in the ori region. (In vitro, RNA I can inhibit primer formation only if it binds to RNA II some time before the complete RNA II–DNA hybrid has been formed; once the nascent RNA II transcript has reached a length of ∼360 nt it becomes resistant to RNA I.) The hybridization of RNA I with RNA II is facilitated/accelerated by a small protein (63

amino acids) encoded by the plasmid gene rop (= rom); the Rop/Rom protein (which acts as a rigid dimer exhibiting exact two-fold symmetry) thus enhances the inhibitory effect of RNA I on primer formation. The ability of RNA I to inhibit primer formation depends on its intracellular concentration. (This, in turn, can be influenced e.g. by the host cell’s RNASE E which can cleave and inactivate RNA I.) It appears that only when the copy number of ColE1 has reached its maximum is the concentration of RNA I high enough to inhibit further replication. Interestingly, the copy number of ColE1 is affected by mutations in the pcnB gene (see MRNA (a)). A similar mechanism for the regulation of plasmid replication occurs e.g. in CloDF13, p15A, pBR322, pMB1 and RSF1030 plasmids. In pBR322, RNA I is synthesized five times more often than RNA II, and it has been estimated that only 1 in 20 pre-priming event results in plasmid replication [JB (1987) 169 1217–1222]. Coleochaete A genus of freshwater epiphytic green algae (division CHLOROPHYTA). Some species are filamentous and dichotomously branched, others are discoid; cell division is confined to apical/marginal cells. Characteristic of the genus is the formation by certain cells of long, fine, unbranched, sheathed ‘hairs’ (setae). Motile cells are scaly. Zoospores are biflagellate, one being formed per cell. Sexual reproduction is oogamous; an envelope of sterile cells may surround the reproductive cells. Plants may be homothallic or heterothallic. Coleosporium See UREDINIOMYCETES. Coleps A genus of freshwater and marine ciliates (subclass GYMNOSTOMATIA). Cells: typically barrel-shaped, ca. 50–100 µm in length, with an anterior (apical) cytostome; a semirigid endoskeleton (formed by the deposition of calcium phosphocarbonate in the pellicular alveoli) gives the appearance of a regular series of platelets forming a grid-like pattern over the entire body surface. Posteriorly directed spines may occur at the posterior edge of the cell. The organisms feed on other protozoa and algae. colibacillosis (vet.) Any of certain diseases, caused by strains of Escherichia coli, which occur primarily in very young animals and which typically involve septicaemia and/or mild to severe diarrhoea. (See also ETEC; cf. WHITE SCOURS; OEDEMA DISEASE.) colicin A A pore-forming colicin (see COLICINS) (MWt ca. 63000) which binds to the OmpF/BtuB protein [mechanism of action: JMB (1986) 187 449–459]. colicin B A pore-forming colicin (see COLICINS) (MWt ca. 80000–90000) which binds to the FEPA PROTEIN. colicin D A colicin (see COLICINS) (MWt ca. 87000) which binds to the FEPA PROTEIN and subsequently inhibits protein synthesis in sensitive cells. [Physical and genetic analysis of the ColD plasmid: JB (1986) 166 15–19.] colicin E A category of COLICINS (MWt ca. 64000–66000) each of which binds to the BtuB protein. E colicins are divided into nine immunity groups (E1. . .E9); colicins of a given group (e.g. E1) are not active against cells which contain a (repressed) plasmid encoding the same colicin and which are synthesizing the corresponding immunity protein. In a sensitive cell, colE1 forms pores; colE2, colE7, colE8 and colE9 are DNases; and colE3 and colE6 are RNases which cleave 16S rRNA. colicin I A category of COLICINS (MWt ca. 80000); colIa and colIb are group B pore-forming colicins. colicin K A group A, pore-forming colicin (see COLICINS) (MWt ca. 70000) which binds to the TSX PROTEIN; uptake across the cell envelope of the target cell is reported to require OmpFA and the TolABQR proteins. 180

colicins colicin L See COLICINS. colicin M A colicin (see COLICINS) (MWt ca. 23000) which binds to the TONA PROTEIN (= FhuA); it inhibits the synthesis of PEPTIDOGLYCAN. colicin N A pore-forming colicin (see COLICINS) MWt ca. 39000) which binds to the OmpF protein. colicin plasmid (col factor, or col plasmid) A PLASMID which encodes one or more COLICINS. Some col plasmids (type 1) are small, MULTICOPY PLASMIDS, while others (type 2) are large, low-copy-number plasmids. The type 1 col plasmids are non-conjugative; type 2 col plasmids are often conjugative (see CONJUGATIVE PLASMID). Conjugative col plasmids occur in various INCOMPATIBILITY (Inc) groups (e.g. ColV is an IncFI plasmid, ColB-K98 is an IncFIII plasmid, and ColIb-P9 is an IncIa plasmid). Some non-conjugative plasmids have been found to exhibit incompatibility [e.g. incompatibility between ColE plasmids: JGM (1986) 132 1859–1862]. Col plasmids contain three essential genes: (i) the colicin structural gene (= ‘activity’ gene); (ii) a gene encoding the immunity protein (see COLICINS); and (iii) a gene encoding the lysis protein. These genes are designated cdl (colicin D lysis gene), cea (colicin E activity gene), cui (colicin U immunity gene) etc. In a population of colicinogenic bacteria only a small proportion of the cells is de-repressed for colicin synthesis; however, the immunity gene is usually expressed constitutively so that cells with repressed genes for the colicin and lysis protein are protected from the given colicin produced by their derepressed neighbours. A col plasmid typically encodes only that type of immunity protein which protects the host cell against the particular colicin encoded by the plasmid. However, ColE9-J encodes two types of immunity protein: one protecting against colE9 and one protecting against colE5 [JGM (1986) 132 61–71]. Transcription of col plasmids is repressed by the LexA protein so that synthesis of colicins is promoted by those agents which trigger the SOS SYSTEM. colicin typing BACTERIOCIN TYPING with COLICINS. colicin U A pore-forming colicin (see COLICINS) (MWt ca. 66300) produced by Shigella boydii ; colicin U binds to sensitive cells via the OmpA and OmpF proteins, and uptake occurs via the TolABQR proteins [JB (1997) 179 4919–4928]. colicin V The designation of a bacteriocin (MWt 6000) which acts by disrupting the membrane potential of sensitive cells [JB (1984) 158 757–759]; it is not inducible by conditions which trigger the SOS system (cf. COLICINS), and at least some authors now classify this bacteriocin as a MICROCIN [e.g. TIM (1998) 6 66–71]. colicin X The designation of a small bacteriocin subsequently classified as a MICROCIN. colicin Y A recently isolated pore-forming colicin (see COLICINS) encoded by plasmid pCol-Let [complete coding sequence: Microbiology (2000) 146 1671–1677]. colicinogenic Able to produce COLICINS. colicinogenic plasmid Syn. COLICIN PLASMID. colicins A category of high-MWt (∼25–90 kDa) BACTERIOCINS produced by colicinogenic bacteria of the family Enterobacteriaceae (e.g. Escherichia coli, Shigella boydii ) and active against (sensitive) strains of the same family; most colicins are encoded by plasmid genes (see COLICIN PLASMID), one exception being the chromosomally encoded ‘bacteriocin 28b’ – a bacteriocin (similar to colicin L) produced by strains of Serratia marcescens. A given colicin is associated with a cluster of three genes: (i) the structural gene for the colicin; (ii) the immunity gene,

encoding a protein which protects the cell against molecules of the same colicin produced by other cells in the vicinity; and (iii) a lysis gene, encoding a protein involved in the release of the colicin. Under normal conditions the colicin and lysis genes are not expressed, but the immunity gene is expressed constitutively. The product of the immunity gene (the immunity protein) inhibits the activity (but not the adsorption) of any molecules of the given colicin that bind to the cell surface. In a population of colicinogenic cells, synthesis of the colicin and lysis protein is promoted under conditions which trigger the SOS SYSTEM (see COLICIN PLASMID). However, in a colicinogenic population a small proportion of the cells (at any given time) may be derepressed for colicin synthesis, and these cells will be able to produce and externalize colicins. Colicins synthesized in a given cell leave the cell following the activity of the lysis protein. The lysis protein localizes in the cell envelope; earlier studies indicated that this causes a non-specific increase in the permeability of the cell envelope – allowing release not only of the colicin molecules but also of various other constituent of the cell’s cytoplasm [EMBO (1987) 6 2463–2468]. During the externalization of colicin molecules, a cell may not appear to be undergoing extensive disintegration, but it becomes leaky (releasing various ions and molecules) and it fails to take up essential substrates. Synthesis and externalization of colicins is characteristically linked to the death of the colicin-producing cell. Cells in the vicinity of a colicin-producing cell are insensitive (‘immune’) to the given colicin if they contain the same (repressed) colicin system and a functional immunity protein. In some cases, however, such immunity may be lost (immunity breakdown) in the presence of high concentrations of the given colicin; this presumably occurs because there are too many molecules of colicin for the cell’s immunity system to deal with. Externalized colicin molecules bind to specific receptors on the surface of sensitive cells, and it appears that internalization of the colicin molecule is usually or always an energy-dependent process; in at least some cases (e.g. colicin A), the colicin unfolds on binding to the receptor, such unfolding being essential for translocation through the cell envelope. The specific receptors used by colicins include the BtuB, FepA, FhuA, IutA and Tsx proteins and the OmpF porin. After binding, group A colicins (A, E1–E9, K, L, N, cloacin DF13 and bacteriocin 28b) are internalized via a complex of envelope proteins that include TolA, TolB, TolQ and TolR. After binding, group B colicins (B, D, Ia, Ib, M, 5 and 10) are internalized via a complex of proteins that include the TONB PROTEIN, ExbB and ExbD. [Colicin import into Escherichia coli cells: JB (1998) 180 4993–5002.] Within the target cell, a given colicin may act as a lethal agent by (i) forming pores in the cytoplasmic membrane, thereby collapsing proton motive force and allowing leakage of cytoplasmic constituents; (ii) functioning as a non-specific DNase; (iii) functioning as an RNase specifically against 16S rRNA; or (iv) inhibiting the synthesis of PEPTIDOGLYCAN. A given colicin is associated with a particular mode of lethal activity. Thus, e.g. pore-formers include the group A colicins E1, A, N and K and the group B colicins B, Ia, Ib, 5 and 10; RNases include group A colicins DF13 and E6; DNases include the group A colicins E2 and E8; inhibitors of peptidoglycan synthesis include the group B colicin M. (See also separate entries for colicin A, B, D, E, I, K, M, N, U, V, X and Y, and CLOACIN DF13.) 181

coliform coliform In general: any Gram-negative, non-sporing, facultatively anaerobic bacillus which can ferment lactose, with acid and gas formation, within 48 hours at 37° C. For water bacteriologists (in the United Kingdom), a coliform is defined as any member of the family Enterobacteriaceae which grows at 37° C and which normally encodes b-galactosidase [for further information see Report 71 (1994) HMSO, London (ISBN 0 11 753010 7)]. Escherichia coli is a typical coliform. coliform mastitis See MASTITIS (b). coliform test A test used to detect the presence of COLIFORM organisms in e.g. water (see INDICATOR ORGANISM and WATER SUPPLIES); the test was originally designed to reveal faecal contamination (hence the designation ‘faecal coliform test’). In the test, aliquots of sample are used to inoculate a number of tubes (see MULTIPLE-TUBE METHOD), each of which contains e.g. MACCONKEY’S BROTH and a DURHAM TUBE; incubation is carried out at 37° C. A ‘positive’ test (i.e. lactose fermentation) is shown by acidification (pH indicator) and gas production (Durham tube). The ‘most probable number’ of coliforms in the original sample can be calculated from the number of positive tubes and the use of statistical tables. The count thus obtained is actually a presumptive coliform count because, in any given tube, a ‘positive’ result could be due to certain endosporeforming bacteria (which also ferment lactose and form gas); this possibility is particularly important when testing chlorinated water samples because spore-forming bacteria are more resistant than coliforms to chlorine. Confirmation that each ‘positive’ result is, in fact, due to thermotolerant (= ‘faecal ’) coliforms involves two further 24-hour tests at 44° C: the INDOLE TEST and the EIJKMAN TEST. ¨ coli-granuloma Syn. HJARRE ’s DISEASE. coliphage A BACTERIOPHAGE that infects Escherichia coli. (For ‘coliphage l’, ‘coliphage T4’ etc see BACTERIOPHAGE l, BACTERIOPHAGE T4, etc.) colisepticaemia A respiratory and septicaemic disease of poultry caused by strains of Escherichia coli. Incidence of the disease has increased greatly with the advent of modern intensive rearing methods, and often occurs secondarily to e.g. poor ventilation, vaccination of birds with live vaccines (e.g. live Newcastle disease vaccines), or various other respiratory diseases (e.g. AIR SACCULITIS, AVIAN INFECTIOUS BRONCHITIS, NEWCASTLE DISEASE). Infection occurs mainly via the respiratory tract; characteristic post-mortem findings include fibrinous pericarditis and perihepatitis. colistins See POLYMYXINS. colitis Inflammation of the colon. (cf. ENTERITIS.) Colitis occurs e.g. in certain infectious diseases (e.g. amoebic and bacillary DYSENTERY; see also SHIGA TOXIN). Antibiotic-associated colitis sometimes occurs when the normal bowel flora is suppressed by broad-spectrum antibiotic therapy; this condition ranges from mild diarrhoea to PSEUDOMEMBRANOUS COLITIS, and is commonly due to growth and toxin formation by Clostridium difficile (an organism normally rare in adults, but common in the bowel in infants). C. difficile produces at least two distinct hydrophobic protein toxins, A (an enterotoxin) and B (a cytotoxin) [JMM (1984) 18 385–391]; toxin A causes fluid accumulation in the intestinal lumen (but not by activating adenylate cyclase – cf. e.g. CHOLERA TOXIN), and the B toxin disaggregates filamentous actin in tissue culture cells [GE (1984) 86 1212 (abstr.)]. [Purification and properties of cytotoxin B: JBC (1986) 261 1316–1321.] Chemotherapy: e.g. vancomycin. colitose (3,6-dideoxy-L-galactose) A sugar, first isolated from Escherichia coli, which occurs in the O-specific chains

of the LIPOPOLYSACCHARIDE in certain Salmonella serotypes (contributing to O antigen 35 in group O salmonellae – see KAUFFMANN–WHITE CLASSIFICATION) and in the LPS of E. coli serotypes of the O111 group. collagen The main protein component of bone, cartilage and other connective tissues; it is a microfibrillar protein whose subunit, tropocollagen, consists of three polypeptide chains in which the amino acid sequences are essentially (glycine-X-Y)n where X and Y are often proline and hydroxyproline, respectively. Collagen is generally resistant to enzymic degradation (cf. COLLAGENASE). Collagenolytic organisms may cause LEATHER SPOILAGE. (See also GELATIN.) collagenase A COLLAGEN-degrading enzyme; collagenases are produced e.g. by Clostridium histolyticum (the b-toxin) and C. perfringens. The collagenase of C. histolyticum appears to have maximum activity at the peptide bond preceding a glycineproline- sequence. collarette See CONIDIUM. Collema A genus of LICHENS (order LECANORALES); photobiont: Nostoc. The thallus lacks a cortex and is homoiomerous, foliose to fruticose, brownish- to greenish-black, pulpy and gelatinous when wet, firm and cartilaginous when dry. The apothecia, when formed, generally have reddish-brown discs. According to species, globular, cylindrical, coralloid or scale-like isidia may be formed. Species occur on bark, rocks, calcareous soils, etc. Colletotrichum A genus of fungi (order MELANCONIALES) which include some important plant pathogens (see e.g. ANTHRACNOSE, COFFEE BERRY DISEASE, RED ROT and SMUDGE). Conidiophores characteristically develop on setose acervuli (see SETA); the conidia, which lack appendages, are typically elongated, roundended and colourless. Collosphaera See RADIOLARIA. Collybia See AGARICALES (Tricholomataceae). colominic acid The capsular polysaccharide of Escherichia coli K1 strains; it is a linear polymer of N-acetylneuraminic acid residues linked by (2 → 8)-a-ketosidic bonds. [Biosynthesis: JB (1984) 159 321–328.] An apparently identical polysaccharide occurs in strains of Neisseria meningitidis (groups B and C). Colominic acid is resistant to most neuraminidases; however, it can be hydrolysed by an enzyme from Clostridium perfringens, and a neuraminidase associated with a bacteriophage (coliphage E) specifically depolymerizes colominic acid [JV (1985) 55 374–378]. colon microflora See GASTROINTESTINAL TRACT FLORA. colonization factor antigens See ETEC. colony (microbiol.) A number of cells or organisms (of a given species) which, during their growth, have developed as a discrete aggregate or group in which there is commonly direct contact or continuity between the cells. Algal colonies. Some algal colonies are of more or less stable size and form (see COENOBIUM sense 2; cf. PALMELLOID PHASE). In some species the colony is the only form in which the organism occurs. See e.g. SCENEDESMUS and VOLVOX. Bacterial colonies are usually formed only on, or within, a solid MEDIUM (such as an agar gel); each usually consists of a compact mass of individual cells, although certain bacteria (e.g. Streptomyces spp) form mycelial colonies. A discrete colony commonly comprises the progeny of a single cell (see also STREAKING). Many species of bacteria can form macroscopic colonies on appropriate media under suitable conditions; on a given medium, a colony’s shape, colour, consistency, surface appearance and size (for a given incubation time) are often highly characteristic, and these features are often of use in the 182

columella identification of particular bacterial species. The full description of a colony can be very detailed. Thus, e.g. the elevation of a (surface) colony may be flat, low convex, domed, umbonate etc; its edge may be e.g. entire (i.e., circular and unbroken), crenate (scalloped), lobed or fimbriate; its texture may be butyrous, friable or mucoid; its surface may be matt or glossy; it may be whitish or pigmented, or it may contain a dye taken up from the medium. When the colonies of certain species develop on blood agar, each colony is surrounded by a zone in which the blood has been lysed or greened (see HAEMOLYSIS). (See also DAISY HEAD COLONIES, DRAUGHTSMAN COLONY, fried egg colony in MYCOPLASMA, MOTILE COLONIES, SMOOTH–ROUGH VARIATION.) Although a bacterial colony has been traditionally regarded as an aggregate of independent cells, some studies have provided evidence that the behaviour of a given cell in a colony is influenced by its position within the colony, i.e., the behaviour of a cell can be subject to ‘multicellular’ regulatory mechanisms [see Book ref. 198, pp. 27–69]. Other types of bacterial colony include e.g. the rosettes of CAULOBACTER spp, the arrays of Hyphomicrobium and RHODOMICROBIUM spp, and the networks of PELODICTYON. Fungal colonies. Some fungi (e.g. certain yeasts) form colonies which resemble those typical of bacteria. Mycelial fungi often form circular ‘fluffy’ colonies, each consisting of a mass of MYCELIUM which may or may not include reproductive structures (see e.g. PENICILLIUM). (See also PELLET sense 2; PETITE MUTANT.) Protozoal colonies. In the (few) colonial protozoa, the colony typically consists of SESSILE (sense 1) organisms which form a group of variable size (see e.g. CARCHESIUM). Chain-like colonies are formed by some members of the ASTOMATIDA. colony-forming unit See COUNTING METHODS. colony hybridization (modified Grunstein–Hogness procedure) A method for screening bacterial colonies for the presence of a specific sequence of DNA (e.g. among colonies containing a gene LIBRARY). As in a REPLICA PLATING procedure, cells are transferred from colonies on the master plate to a nitrocellulose (or other) filter. The cells on the filter are lysed with alkali – the alkali also serving to denature the DNA (i.e. to separate the strands of the duplex); the alkali is then neutralized, any protein is digested e.g. with proteinase K, and the filter is baked at 70–80° C under vacuum to bind the (single-stranded) DNA to the filter. The filter is then exposed to labelled probes (see PROBE) which are complementary to the sequence of interest. After washing away unhybridized probes, the given sequence, if present, is indicated by the label on bound (hybridized) probes; any probe-positive sites on the filter are then used to identify the corresponding (positive) colonies on the master plate. A probe labelled with a radioactive isotope is detected by AUTORADIOGRAPHY. In the original procedure [Book ref. 177, pp. 172–174], cells transferred from the master plate were allowed to grow and form colonies on the filter (which was overlaid on a plate of nutrient medium); subsequent steps were similar to those described. This technique can also be used for yeast cells, but these cells must be converted to sphaeroplasts (with e.g. ZYMOLYASE) before lysis. colony-stimulating factors (CSFs) CYTOKINES involved in the maturation of LEUCOCYTES. CSFs include e.g. granulocyte–macrophage colony-stimulating factor (GM-CSF), an agent which stimulates proliferation of progenitors of various blood cells (including granulocytes and macrophages), and macrophage colony-stimulating factor (M-CSF; also referred to as CSF-1), an agent formed mainly by monocytes and

macrophages which, among other functions, stimulates the development of macrophages from precursor forms such as monoblasts and monocytes. Colorado tick fever An acute human disease caused by a virus and transmitted by the tick Dermacentor andersoni ; it occurs in the Rocky Mountain regions of the USA. Symptoms include fever, leucopenia, headache and myalgia, but no rash; CNS complications occasionally occur in young children. Wild rodents (e.g. ground squirrels) may act as a reservoir of infection. The causal agent has been regarded as an ORBIVIRUS, but has been shown to contain 12 dsRNA molecules [Virol. (1981) 112 361–364] and may thus represent a distinct taxonomic group. colostrum A secretion of the mammary gland produced before lactation proper; it contains e.g. immunoglobulins (mainly IgA and IgG). In man, the immunoglobulin content of colostrum is relatively low, but in some animals – e.g., ruminants (in which immunoglobulins do not cross the placenta) – large amounts are normally present. (See also PASSIVE IMMUNITY.) colour-breaking (breaking) The development of VARIEGATION in flower petals; colour-breaking may occur as a result of virus infection (e.g., in tulips infected with tulip breaking virus, a member of the POTYVIRUSES). Flowers affected in this way are often prized for their attractive appearance. Colour Index (CI) A comprehensive reference publication on dyes and pigments published by The Society of Dyers and Colourists, Bradford, Yorkshire BD1 2JB, England. It consists of a number of volumes which are periodically updated. coloured field illumination Syn. RHEINBERG ILLUMINATION. colourless sulphur bacteria Those non-photosynthetic SULPHUR BACTERIA which obtain energy by the oxidation of sulphur and/or reduced inorganic sulphur compounds (e.g. sulphide); although referred to as ‘colourless’, some strains can exhibit pigmentation owing to their content of cytochromes. The colourless sulphur bacteria include e.g. species of Beggiatoa and Thiobacillus. [Ecology of colourless sulphur bacteria: Book ref. 115, pp. 211–240.] Colpidium A genus of ciliates (order HYMENOSTOMATIDA) which occur e.g. in freshwater habitats containing decomposing organic matter. Cells: ovoid or reniform, ca. 50–150 µm, with uniform somatic ciliature and a single macronucleus, micronucleus and contractile vacuole. In C. colpoda (at least) asexual reproduction occurs within a cyst. Colpoda A genus of soil and freshwater ciliates (order COLPODIDA). Cells: typically reniform, ca. 40–120 µm in length, with uniform somatic ciliation; the cytostome is lateral. C. steini is a small species, ca. 20–60 µm, with a conspicuous tuft of cilia (the ‘beard’) projecting from the region of the vestibulum. Food consists of other protozoa, algae and bacteria. Asexual reproduction occurs within CYSTS – in which four or more individuals may be formed. Colpodida An order of protozoa (subclass VESTIBULIFERIA) in which the vestibular ciliature tends to be highly organized. Cysts are common. The organisms are typically free-living, sometimes associated with molluscs. Genera: e.g. COLPODA, Woodruffia. Colpomenia See PHAEOPHYTA. Colsargen See SILVER. Columbia SK virus See CARDIOVIRUS. columella An axial or central, unicellular or multicellular structure within a fruiting body in certain fungi and in certain slime moulds of the MYXOMYCETES; in some cases it is simply an extension of the sporangiophore into the cavity of a sporangium, while in others it may be a spherical, conical or cylindrical structure extending upwards from the base of a sporangium. Although 183

column fermenter (T. brevifaciens); affected plants show severe stunting and chlorotic flecks on the leaves. (cf. KARNAL BUNT; see also CEREAL DISEASES.) common cold An acute disease of the upper respiratory tract in man; the causal agent may be any of a range of viruses – usually a rhinovirus, coronavirus, influenza virus (type A, B or C), parainfluenza virus (types 1–4) or human respiratory syncytial virus. Incubation period: usually ca. 48–72 hours. Symptoms typically include coryza and nasal obstruction, sore throat, cough, sneezing, but little or no fever. Direct contact may be an important mode of transmission of rhinoviruses [AIM (1978) 88 463]; the other viruses are probably transmitted mainly by aerosols (see DROPLET INFECTION). Transmission of rhinoviruses can be interrupted (experimentally) by the use of virucidal (citric acid-treated) paper handkerchiefs [JID (1986) 153 352–356]. Colds are usually self-limiting, but occasional complications include e.g. OTITIS MEDIA, PNEUMONIA or SINUSITIS. (cf. INFLUENZA.) [Review: Lancet (2003) 361 51–59.] common fimbriae Type 1 FIMBRIAE. common pili (1) Syn. FIMBRIAE. (2) Syn. Type 1 fimbriae. common scab (of potato) See POTATO SCAB. communicable disease Syn. INFECTIOUS DISEASE. comoviruses (cowpea mosaic virus group) A group of PLANT VIRUSES in which the bipartite positive-sense ssRNA genome is encapsidated in (separate) icosahedral particles; both parts are necessary for infection. Most comoviruses cause systemic mosaic or mottling and stunting – occasionally with wilting, necrotic ring formation, etc. – in various plants, including e.g. cowpea (Vigna unguiculata), beans, red clover etc; the host range of individual members is narrow. Most comoviruses are transmitted by leaf-feeding beetles, particularly of the Chrysomelidae (e.g. Cerotoma and Diabrotica spp); seed transmission occurs in some comoviruses, and mechanical transmission can occur readily under experimental conditions. Type member: COWPEA MOSAIC VIRUS (SB isolate). Other members: e.g. cowpea severe mosaic virus, quail pea mosaic virus, red clover mottle virus, squash mosaic virus. (cf. BROAD BEAN WILT VIRUS.) ComP See QUORUM SENSING. compact colony-forming active substance See CCFAS. comparative single intradermal tuberculin test (comparative test; single intradermal comparative tuberculin test) (vet.) A form of TUBERCULIN TEST, applied to cattle, in which two intradermal injections are given (on a single occasion – cf. STORMONT TEST) at different sites on the same side of the neck; PPD derived from Mycobacterium bovis is injected at one site, PPD derived from M. avium is injected at the other site. After 72 hours any increase in skin thickness at the injection sites is measured. If the response to PPD from M. bovis (increase in skin thickness) is greater than that to PPD from M. avium by a certain minimum amount then the animal is designated a ‘reactor’. A positive reaction to PPD from M. avium together with a negative reaction to PPD from M. bovis suggests contact with M. avium and/or mycobacteria other than M. bovis. The use of a defined antigen (ESAT-6), compared with PPD, has been associated with lower sensitivity but higher specificity [VR (2000) 146 659–665]. comparative test (vet.) Syn. COMPARATIVE SINGLE INTRADERMAL TUBERCULIN TEST. comparator See WATER SUPPLIES. compatibility (1) (of plasmids) See PLASMID. (2) (in fungal sexuality) The ability, or otherwise, of a given cell or thallus to interact sexually with itself and/or with other cells or thalli of the same species. In general, the genetic constraints on mating increase, both in number and complexity, from the lower

columellae are commonly described as STERILE (sense 2), the columellae of Mucor piriformis have been reported to germinate and give rise to secondary sporangia under certain cultural conditions [Mycol. (1985) 77 353–357]. (cf. PSEUDOCOLUMELLA.) column fermenter See FERMENTER. columnaris disease (cotton wool disease; ‘mouth fungus’) An acute, often fatal freshwater FISH DISEASE caused by Flexibacter columnaris. Necrotic lesions occur on the skin and gills; cottony tufts of epithelium and bacteria appear around the mouth. ColV plasmid Any of a heterogeneous group of IncFI COLICIN PLASMIDS which encode COLICIN V; many also encode e.g. the aerobactin iron-uptake system (see SIDEROPHORES). ColV, I-K94 plasmid An IncFI COLICIN PLASMID which encodes COLICINS V and Ia; it occurs e.g. in Escherichia coli and is derepressed for conjugal transfer. ColX plasmid See COLICIN PLASMID. ComA See QUORUM SENSING. Comatricha See MYXOMYCETES. comb. nov. (combinatio nova; new combination) In NOMENCLATURE: the name of a species which has been moved from one genus to another but which has retained the specific epithet (suitably modified, when necessary, to agree with the form of the new genus name). combinatio nova See COMB. NOV. combined gold standard See GOLD STANDARD. combined residuals See WATER SUPPLIES. combining site (immunol.) That part of an ANTIBODY (or a FAB PORTION) which can combine with a determinant of the homologous antigen or hapten; it is located at the variable (Nterminal) ends of the heavy chain and light chain in an Ig molecule (see IMMUNOGLOBULINS and HYPERVARIABLE REGION). Monomeric antibodies have a VALENCY of two. (See also CYTOPHILIC ANTIBODIES and AFFINITY LABELLING.) come-up time In the CANNING process: the time needed for the correct processing temperature to be reached in the retort. comedone See ACNE. co-metabolism The phenomenon in which a substrate (the cosubstrate) which does not support the growth of a given microorganism can nevertheless be modified or degraded by that organism in the presence of a second, growth-supporting substrate. Co-metabolism is believed to result from the action of an enzyme of relatively low substrate specificity which has a different physiological function in the cell; for example, METHANE MONOOXYGENASE can oxidize certain short-chain alkanes and alkenes as well as methane, and such hydrocarbons can be oxidized by methane-grown cells (co-oxidation) which may be unable to use the oxidation products. In nature, co-metabolism may be important in the degradation of XENOBIOTICS. commensal See COMMENSALISM. commensalism SYMBIOSIS (sense 1) in which one symbiont (the commensal ) derives benefit from the association, and the other (sometimes called the host) derives neither benefit nor harm. (cf. MUTUALISM.) commercial sterility A term used when referring to the condition of a substance following APPERTIZATION. common bunt A seed-borne wheat disease caused by Tilletia caries or T. foetida (T. laevis). (Rye and certain other grasses may also be affected.) Symptoms include retarded growth and the formation of long, narrow ears which have a bluish tinge; grains are filled with grey or black powdery masses of teliospores which, when released during harvesting, give off a characteristic ‘rotten fish’ odour (trimethylamine). Dwarf bunt is a similar (soil- and seed-borne) disease caused by Tilletia contraversa 184

complement fixation Complement fixation can be triggered in various ways, the type of trigger determining which pathway is followed; four pathways are shown in the figure. (a) Classical pathway. This pathway is activated e.g. when antigens bind to COMPLEMENT-FIXING ANTIBODIES in the presence of complement. When such binding occurs, sequentially activated components may bind at or near the antigen–antibody complex; according to the antigen involved, this may result in e.g. phagocytosis of the antigen–antibody complex or, if a cellsurface antigen is involved, it may lead to cell lysis (see later). The cascade of reactions which occur in the (antigen-triggered) classical pathway is as follows. The sequence is triggered when two or more subunits of C1q (in the complement C1 molecule) bind to the FC PORTION of antigen-bound IgG or IgM antibodies. Such binding (dependent on calcium ions) activates the C1r component of C1 which, in turn, activates the C1s component. C1s has serine protease and esterase activity. (Note that antibody-independent activation of C1 can be promoted by certain non-specific activators – e.g. C-reactive protein (an ACUTE-PHASE PROTEIN) and various proteases.) Activated C1s cleaves C4, forming C4a and C4b; as one molecule of C1s can cleave many molecules of C4, this reaction provides initial amplification. C4b molecules can bind to bacterial or other surfaces; like C3b (see later), C4b is an OPSONIN: C4b-coated cells or particles bind (via C4b) to the CR1 receptor on the surface of phagocytes. Surface-bound C4b may also bind C2. C2 is cleaved (in a process involving C1s) to C2a and C2b; the complex formed between the larger fragment, C2a (referred to as C2b in some sources), and C4b (C4b2a) is a C3 convertase: an enzyme which cleaves C3 to C3a and C3b (this being a major phase of amplification in the complement cascade). (A low level of C3 cleavage normally occurs spontaneously (‘C3 tickover’) but the resulting fragments are rapidly degraded.) C3a is an ANAPHYLATOXIN. C3b is an important OPSONIN, promoting e.g. the phagocytosis of pathogens (IMMUNE ADHERENCE); C3b-bound antigens bind (via C3b) to CR1 receptors on phagocytes. C3b can also form a complex with C3 convertase: C4b2a3b; this complex is a C5 convertase, i.e. it cleaves C5 into the small fragment C5a and a larger fragment, C5b. C5a is an ANAPHYLATOXIN and a chemoattractant for phagocytes (e.g. neutrophils). C5b, C6 and C7 form a complex (C5b67) which binds to cell membranes – typically at the site of the initial triggering event. Component C8 binds to the complex; this promotes polymerization of a number of C9 molecules within the membrane – the C9 molecules forming a pore or channel which, in some types of cell (or even LIPOSOMES), can lead to lysis (immune cytolysis). C5b678 and the C9 molecules collectively form the so-called membrane attack complex, MAC. (Even in the absence of C9, the complex C5b678 can bring about slow lysis e.g. in erythrocytes.) For certain pathogens (e.g. trypanosomes), MAC-inflicted damage can be lethal. In Gram-negative bacteria, pores formed by the MAC in the OUTER MEMBRANE can promote cell lysis by giving LYSOZYME access to cell-wall peptidoglycan; thus, e.g. a Gram-negative bacterium on the conjunctiva would be at risk of lysis because the tear film normally contains both complement and lysozyme. Sometimes, C5b67 binds to a cell other than that which triggered the cascade; MAC-inflicted lysis in such a cell is called

fungi, through the ascomycetes, to the basidiomycetes. HOMOTHALLISM is common in all the major groups of fungi. Bipolar HETEROTHALLISM occurs in some lower fungi (e.g. species of Mucor and Rhizopus), in many ascomycetes (including e.g. Saccharomyces), and in many of the rust and smut fungi. Tetrapolar heterothallism occurs in a number of basidiomycetes – including e.g. Schizophyllum commune and Ustilago maydis. (See also MATING TYPE and PARASEXUAL PROCESSES.) compatible (plant pathol.) Refers to a plant–pathogen interaction which results in the development of disease in the plant. (cf. INCOMPATIBLE.) compatible solute Any low-MWt compound which, when present intracellularly in high concentration, is compatible with metabolism and growth. Compatible solutes involved in OSMOREGULATION include: L-glutamate, GLYCEROL, ISOFLORIDOSIDE, MANNITOL, L-proline, glycine betaine [in Escherichia coli : FEMS Reviews (1994) 14 3–20; in Staphylococcus aureus: Microbiology (1994) 140 3131–3138], and certain sugars. compensation level See PHOTIC ZONE. competence See TRANSFORMATION (1). complement (C or C′ ; historical syn. alexin or alexine) (immunol.) A group of functionally related proteins present in normal plasma, tissue fluids and the (freshly isolated) serum of vertebrates. (In serum, the activity of complement is abolished by exposure to room temperature for a few days, by heating to 56° C for 30 minutes, or by the action of chelating agents such as EGTA or oxalate.) When activated, the complement system is responsible for a number of important physiological activities (see e.g. COMPLEMENT FIXATION). Before activation, many of the components exist as proenzymes and/or inactive forms (cf. FACTOR D) which, on activation, complex with, or act on, other components to form physiologically active entities. In man, complement consists of nine numbered components (C1–C9, MWts ca. 80000–200000) together with various proteins involved e.g. in stabilization or control functions: see e.g. FACTOR B; FACTOR D; FACTOR H; FACTOR I; PROPERDIN and S PROTEIN. Component C1 is a complex macromolecule which consists of three parts: C1q, C1r and C1s; C1q itself consists of a bundle of six elongated subunits, and the macromolecule as a whole depends on Ca2+ for its structural integrity. Gene-based deficiencies in the complement system are associated with various adverse effects – which depend e.g. on the particular component(s) involved. One important role of complement is the removal of immune complexes (via the liver), and deficiencies in C1, C4 and C2 may give rise to forms of disease reflecting the accumulation of such complexes. A deficiency in C3 (with reduced capacity for opsonization) may result in recurrent infections. A deficiency in MBL (lectin pathway) is associated with increased susceptibility to infection in children. Deficiencies in C5–C8 generally cause increased susceptibility to infection – particularly with Neisseria. complement activation Syn. COMPLEMENT FIXATION. complement fixation (complement activation) Activation of the COMPLEMENT system, i.e. promotion of the sequence (‘cascade’) of reactions in which various components of complement are activated in turn. In vivo, complement fixation is involved e.g. in certain immune responses and in INFLAMMATION; in vitro it provides a sensitive system for various COMPLEMENTFIXATION TESTS. (Complement fixation is sometimes referred to as complement inactivation – an allusion to the fact that components of complement are ‘used up’ during fixation.) 185

complement fixation CLASSICAL

LECTIN

ALTERNATIVE

C4

C4, C2 MBL MASPs

C3b LPS etc.

C1−ag−ab

C4b

C3bB

factor D properdin

C2

C4b2a

amplification loop

factor B

PC3bBb

(C3 CONVERTASE)

C2a

factor I (in plasma)

(C3 CONVERTASE)

C3

C3

C3b

C3b

C3b C3bi

C4b2a3b

P(C3b)2Bb

(C5 CONVERTASE)

C5

(C5 CONVERTASE)

(as in classical pathway)

C5b C6

C5b6

C7, 8, 9

C5b6789

(MEMBRANE ATTACK COMPLEX)

COMPLEMENT FIXATION: four pathways (simplified scheme; see text). C1, C2 etc. denote particular components of the complement system; ‘a’ and ‘b’ denote fragments of components produced by enzymic cleavage during the activation process. For clarity, the diagram does not show all the cleavage products; for example, C4 is cleaved to C4a and C4b, but only the C4b fragment is considered here. Dotted lines indicate those cases in which a given complex or component acts enzymically to cleave certain components of the system. Reproduced from Bacteria 5th edition, Figure 11.1, page 292, Paul Singleton (1999) copyright John Wiley & Sons Ltd, UK (ISBN 0471-98880-4) with permission from the publisher.

C1INH), which inhibits initial activation of the classical pathway, and FACTOR I, which cleaves C3b to an inactive form, C3bi. (C3bi, although inactive in the cascade, can nevertheless behave as an opsonin – binding e.g. to the CR4 receptor on macrophages.) Other regulatory factors are involved in the control of the alternative pathway (see later). (b) Alternative pathway. In evolutionary terms, this pathway is apparently older than the classical pathway. In man, fixation via the alternative pathway is initiated by e.g. bacterial LIPOPOLYSACCHARIDES, rabbit (but not sheep) erythrocytes, aggregates of

bystander lysis or reactive lysis. Reactive lysis may thus damage cells adjacent to a site of infection, and to limit such damage the plasma contains factors inhibitory to the C5b67 complex (see e.g. S PROTEIN). Because complement fixation creates highly potent physiological agents, and as it includes various stages of amplification, regulatory mechanisms are essential to prevent the system becoming an uncontrolled avalanche of physiological destruction. In fact, there are specific inhibitors at key stages in the process; these include C1EI (C1 esterase inhibitor; also called 186

complementation test human myeloma proteins, inulin and ZYMOSAN. (In the human complement system, this pathway can be activated by sheep erythrocytes if the cell-surface sialic acids have been removed.) The sequence of reactions in this pathway is as follows. On a suitable surface (e.g. OUTER MEMBRANE LPS), component C3b (‘tickover’ C3b – see above) binds FACTOR B (in the presence of Mg2+ ) to form C3bB. The bound factor B is then cleaved by FACTOR D; this creates a C3 convertase (C3bBb) which is stabilized by binding to PROPERDIN (P). The C3 convertase (PC3bBb) cleaves C3, forming more C3b and giving rise to an amplification loop (see figure). The C3 convertase can bind a molecule of C3b to form a C5 convertase (P(C3b)2 Bb); the cascade then continues as in the classical pathway. Regulators of the alternative pathway include the plasma protein FACTOR I and the cell-bound decay-accelerating factor (DAF) (see CD55). Other cell-surface-associated inhibitory proteins include CR1, which can displace Bb from surface-bound C3bBb, and the membrane co-factor protein (MCP), which facilitates cleavage of C3b by factor I; collectively, these cell-surface factors help to protect host cells from the ongoing complement cascade (including the MAC) by inhibiting the cascade at the C3 convertase/C3b level. For experimental work on the alternative pathway, COBRA VENOM FACTOR is used as an activator, while COMPLESTATIN and HEPARIN are used as inhibitors. (See also SURAMIN.) When the classical pathway is stimulated, some of the C3b can bind Factor B and give rise to an alternative-pathway C3 convertase; in this way the alternative pathway can augment the classical pathway, and this sequence of reactions is sometimes called the amplification pathway. The alternative pathway can be studied independently of the classical pathway by using the Ca2+ chelator EGTA (the latter pathway being dependent on the presence of calcium ions). (c) The lectin pathway. This pathway effectively bypasses the C1 stage of the classical pathway: when the lectin pathway is triggered, a C3 convertase (C4b2a) is formed directly from C4 and C2. The lectin pathway involves several components of normal plasma: mannose-binding lectin (MBL) and the MBL-associated serine proteases (MASPs) (cf. component C1s in the classical pathway); the system is triggered when MBL binds to certain groups on the microbial cell envelope. [Mannose-binding lectin: IT (1996) 17 532–540.] The lectin pathway may be particularly useful in the young during the ‘window’ period of ∼12–18 months between loss of maternal antibody cover (IgG) and the development of an effective immune system. However, triggering of this pathway by a bacterial pathogen may be greatly inhibited if the pathogen has a capsule (e.g. Neisseria meningitidis). (d) The C2a pathway (= ‘salvage pathway’). This pathway, reported in 1997, may be important in the context of pathogenic mycobacteria. In the C2a pathway, C2a acts as a C3 convertase when it binds to the mycobacterial surface. [See TIM (1998) 6 47–49; TIM (1998) 6 49–50.] complement-fixation test (CFT) Any of a range of sensitive, in vitro tests in which COMPLEMENT FIXATION is used to indicate the presence or absence (or quantity) of a specific antigen or COMPLEMENT-FIXING ANTIBODY. Principle: antigen and antibody are allowed to interact in the presence of complement, and the amount of complement used up (a measure of the amount of antigen–antibody interaction) is estimated, indirectly, by the addition of a HAEMOLYTIC SYSTEM; the proportion of erythrocytes

lysed indicates the amount of free (unfixed) complement remaining. Practice: to detect or quantify e.g. a given antibody in a sample of serum, SERIAL DILUTIONS of the INACTIVATED SERUM are prepared, and known, fixed quantities of COMPLEMENT and antigen are added to each dilution; the quantity of complement added (determined by titration) should be sufficient to cause lysis of ca. 90% of the erythrocytes in the haemolytic system when no complement-fixation has occurred. Incubation is carried out for ca. 18 hours at ca. 4° C. (Low-temperature incubation is used because some components of complement are labile at room temperature.) A fixed volume of the haemolytic system is then added to each dilution, and the whole is incubated for 15–30 min at 37° C; the test dilutions are then left at ca. 4° C to permit non-lysed erythrocytes to settle. In any given dilution, the extent of haemolysis will be inversely proportional to the extent of complement fixation in that dilution. If maximum haemolysis is observed in the lowest serum dilution (i.e. the highest serum concentration) the test is negative – i.e. the serum contains no detectable antibody. In a positive test, no haemolysis occurs in (at least) the lowest serum dilution; a test may be regarded as positive either (i) when no haemolysis has occurred in a specified number of serum dilutions (e.g. all dilutions up to 1:8 or 1:16 initial serum dilution), or (ii) when an increase in the titre of complement-fixing antibodies is recorded in a second serum sample taken some time after the first. In all CFTs, controls are essential e.g. to check that the test system is functioning correctly and to preclude false-positive interpretations based on the effects of ANTICOMPLEMENTARY substances. complement-fixing antibodies Antibodies which ‘fix’ or ‘activate’ COMPLEMENT when they combine with their homologous antigens. IgG (subclasses 1 and 3) and IgM can bring about complement fixation via the classical pathway; aggregates of IgA (subclasses 1 and 2) can activate the alternative pathway. (See also FC PORTION.) complement receptor 1 See CD35. complementarity-determining regions (immunol.) Those HYPERVARIABLE REGIONS which occur at the surface of the COMBINING SITE of an antibody. complementary bases See BASE PAIR. complementation The ability of a gene (or protein) to compensate for (i.e., to ‘complement’) a functional defect in a homologous gene (or protein) when present in the same organism or cell. For example, a wild-type gene necessary for the synthesis of a given amino acid may, when introduced into a mutant organism auxotrophic for that amino acid, complement the mutant gene (by supplying an active form of the defective gene product) and restore the wild-type (prototrophic) phenotype. (See also COMPLEMENTATION TEST; IN VITRO COMPLEMENTATION ASSAY; NON-GENETIC REACTIVATION.) complementation test A test used to determine whether or not COMPLEMENTATION will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell. The test involves bringing together, into the same cell, the two (haploid) mutant genomes (or a genome and part-genome – see MEROZYGOTE) and determining the resulting phenotype. The expression of a wildtype phenotype (a positive complementation test) indicates that the mutations are in different genes in the two genomes, i.e., one wild-type form of each gene can be supplied by each of the mutant genomes (intergenic or intercistronic complementation); this indicates that at least two genes are involved in the expression of that phenotype. (If the mutations were in the 187

complementing diploids same gene in each genome, no wild-type form of that gene would be present and the mutant phenotype would continue to be expressed; if such a negative result is consistently obtained with a range of mutants of the same phenotype, then the phenotypic characteristic under study may be presumed to be under monogenic control.) Interpretation of the results of a complementation test can be complicated by several factors. (a) In some cases two mutant copies of a gene – each by itself encoding an inactive polypeptide – may be able to complement one another when present together in the same organism. This may occur e.g. when the normal active gene product is a monomer of an oligomeric protein, and the two types of defective monomer encoded by the two mutant alleles can somehow interact to give an oligomer with some activity (intragenic, intracistronic or interallelic complementation). The resulting phenotype usually has characteristics qualitatively or quantitatively intermediate between the wild-type and mutant phenotypes. (b) Certain mutant genes are dominant over their wild-type alleles: e.g., an inactive product of a mutant gene may bind to the active product of the wild-type gene to produce an inactive hybrid oligomer (negative complementation: see e.g. LAC OPERON); such dominant mutations can be detected by a CIS–TRANS TEST. (c) Recombination between two mutant copies of a gene may result in the restoration of a functional gene; this possibility can be minimized by using recombination-deficient strains (e.g. recA− bacteria). (d) Complementation can occur only if the genes under study produce diffusible products; it cannot occur e.g. if the mutation is in a control region (e.g. a promoter) which can affect the expression only of adjacent genes in the same genomic molecule. (See also CIS-DOMINANCE.) (e) A POLAR MUTATION can give a misleading result since a single mutation can inactivate two or more adjacent genes. (See also CISTRON.) complementing diploids See PROTOPLAST FUSION. complestatin A substance, produced by Streptomyces lavendulae, which inhibits the alternative pathway of COMPLEMENT FIXATION by combining with Factor B and preventing its binding to C3b. complete Freund’s adjuvant See FREUND’S ADJUVANT. complete medium (CM) A type of culture medium which contains nutrients sufficient to support the growth of both PROTOTROPHS and AUXOTROPHS. (cf. MINIMAL MEDIUM.) complete transduction See TRANSDUCTION. complex flagellum See FLAGELLUM (a) and FLAGELLIN. complex-mediated hypersensitivity Syn. TYPE III REACTION. composting A process involving the aerobic biological degradation of waste plant matter (e.g. straw, cotton waste, corn-cobs etc) or other organic waste (e.g. paper, dewatered sewage sludge, municipal refuse); composting reduces the bulk of the waste material and converts it to an innocuous form (‘compost’) which can be used e.g. as a soil conditioner. (See also MUSHROOM CULTIVATION.) Composting involves the activities of a succession of microorganisms whose nature depends to some extent on the nature of the material being composted. In the composting of e.g. wheat-straw: the damp straw is piled loosely (to allow free circulation of air); inorganic nitrogen and phosphorus – or animal or poultry manure – may be added. The activities of mesophilic bacteria generate heat, and the temperature in the centre of the heap may rise to ca. 60° C or more within a few days, creating conditions in which thermophilic actinomycetes predominate [ARM (1983) 37 198–200]. Air circulation is maintained by convection,

and the heap may be turned and mixed at intervals. The pH may rise substantially (e.g. to 8–9), due e.g. to ammonia production, but later falls to ca. 6–7. After several days the temperature may fall to ca. 30–50° C and may remain at this level for several weeks; during this stage fungi become dominant. Initially, thermophilic members of the Mucorales (e.g. Rhizomucor pusillus) develop; these are then replaced by thermophilic hyphomycetes (e.g. Humicola spp, Thermomyces lanuginosus) and ascomycetes (e.g. Chaetomium thermophilum). Finally, basidiomycetes such as Coprinus cinereus (often accompanied by the zygomycete Mortierella wolfii ) become dominant [Book ref. 39, pp. 263–305]. During composting, most or all of the free soluble substrates, much of the CELLULOSE, HEMICELLULOSES and PECTIC POLYSACCHARIDES, and some of the LIGNIN, are degraded, and the loss in dry weight may reach 50% or more. compound II See SIDEROPHORES. compound ciliature Any form of somatic or oral ciliature which involves a discrete group of cilia (several to many) acting as a functional unit; examples: the CIRRUS, MEMBRANELLE, PARORAL MEMBRANE and SYNCILIUM. compound trichocyst Syn. FIBROCYST. Compsopogon See RHODOPHYTA. co-mutagenesis The generation of two or more mutations at closely linked loci: see e.g. MNNG. ComX See QUORUM SENSING. con gene See OMP. concanavalin A (con A; jack bean lectin) A mitogenic LECTIN (tetrameric form: MWt 102000) from the jack bean, Canavalia ensiformis; it can stimulate T cells and, if cross-linked (e.g. by anti-con A antibody), B cells. Con A binds e.g. to terminal a-D-mannopyranosyl and a-D-glucopyranosyl residues (binding requires Ca2+ and Mg2+ ), and can thus agglutinate e.g. bacteria whose cell wall TEICHOIC ACIDS contain a-linked glucosyl substituents. concatemer Two or more identical linear nucleic acid molecules (e.g. copies of a viral genome) in tandem, i.e., covalently linked end to end in the same orientation. (cf. CATENANE.) concatenate (1) (verb) To form a concatenate (sense 2). (2) (noun) Syn. CATENANE or CONCATEMER. (3) (adj.) Of e.g. spores: formed in chains. concentration exponent (of a disinfectant) See DILUTION COEFFICIENT. concentric bodies (mycol.) Rounded or ellipsoidal intracellular structures (ca. 300 nm diam.) which have a transparent core surrounded by concentric layers of varying optical density; they occur in almost all lichenized ascomycetes and in a few nonlichenized ascomycetes. Their origin and function are unknown. Similar structures (‘concentric granules’) are found in Allomyces and related genera; these may play a role as septal pore plugs [Mycol. (1987) 79 44–54]. (cf. CELLULIN GRANULES.) conceptacle (mycol.) A hollow structure within which spores are formed – e.g. a locule (see ASCOSTROMA). conchate Having the shape of one-half of a bivalve shell. Conchocelis stage See e.g. PORPHYRA. concolorous Similarly coloured. concomitant immunity Syn. PREMUNITION. condenser (substage condenser) In a microscope: a system of lenses which concentrates light and directs it onto the specimen (see MICROSCOPY, Fig. 1). Correct adjustment of the condenser ¨ is important for optimum image formation: see e.g. KOHLER ILLUMINATION. The numerical aperture of a condenser (see RESOLVING POWER) should be at least as great as that of the objective lens with which it is used; an oil-immersion 188

conidium conidiogenous cell See CONIDIUM. conidioma Any plectenchymatous structure which bears conidia – e.g. a pycnidium, sporodochium or synnema. conidiophore A hypha which bears one or more conidiogenous cells (see CONIDIUM). In e.g. some species of Colletotrichum, setae (see SETA) can function as conidiophores. conidiospore Syn. CONIDIUM. conidium (mycol.) An asexually-derived, non-motile SPORE formed in a blastic or thallic mode (see below) from a specialized conidiogenous (i.e., conidium-producing) cell (cf. SPORANGIOSPORE). Conidia are formed e.g. by many fungi of the DEUTEROMYCOTINA and by a few lower fungi (e.g. species of Bremia and Peronospora). The two basic modes of conidiogenesis (conidium formation) are as follows. Blastic conidiogenesis. An apical or lateral part of a conidiogenous cell expands and develops into a mature conidium, becoming delimited from the parent cell by a septum. Such a blastic conidium (= blastoconidium or blastospore) secedes (i.e., breaks away) from the conidiogenous cell by centripetal splitting of the septum (schizolysis) – half the septum becoming the base of the conidium, the other half forming the apex of the conidiogenous cell. If the conidiogenous cell subsequently elongates from a basal growing region it is said to exhibit basauxic development. (Cessation of hyphal tip growth – see GROWTH (b) – preceding blastic conidiogenesis may depend on changes in ion gradients across the envelope of the conidiogenous cell.) Thallic conidiogenesis. A septum-delimited part of a hypha becomes converted to a single, terminal or intercalary, conidium (a holothallic conidium) or to a chain of conidia (arthric conidia). (cf. ARTHROSPORE.) Secession of a terminal, holothallic conidium commonly occurs by rhexolysis: the circumferential splitting of the wall of the penultimate cell (which ruptures) a little below the septum of the conidium; arthric conidia may separate by rhexolysis (alternate cells being sacrificed) or by schizolysis. [Formation and germination of fungal arthroconidia: CRM (1986) 12 271–292.] There are various ways in which the conidiogenous cell can produce a succession of conidia or give rise to a crop of simultaneously formed conidia; some examples are given below. (a) Ampullate development. The apex of the conidiogenous cell becomes globose (‘ampullate’) and gives rise, simultaneously, to a number of blastoconidia. Ampullate development occurs e.g. in Gonatobotrys. (b) Annellidic development. After the first, terminal blastoconidium has been delimited by a septum (and either before or after its secession) a new wall is laid down on the inner surface of the old wall in the distal region of the conidiogenous cell; this new, annular wall, in conjunction with the apical septum, forms an inverted cup-like structure at the free end of the conidiogenous cell. (The formation of the new wall is referred to as enteroblastic proliferation of the conidiogenous cell.) Subsequently, the cup-like structure expands to form the next conidium; such a process, in which the new wall becomes continuous with the conidial wall, is referred to as holoblastic conidial development. Septum formation then delimits the second blastoconidium – which (sooner or later) secedes by schizolysis; the position of this septum is such that, following secession of the blastoconidium, part of the new wall remains in the conidiogenous cell, extending a little beyond the rim of the old wall. Thus, after a number of blastoconidia have been produced, the conidiogenous cell (annellide) exhibits a succession of bands (annellations) at the apical end, each annellation being the remnant of a layer of wall formed inside the previous layer.

condenser should be used with an oil-immersion objective. Before entering the condenser, the light passes through an iris diaphragm (aperture diaphragm, substage diaphragm) which, by controlling the amount of light entering the condenser, controls the apical angle of the cone of light which illuminates the specimen. Hence, the aperture diaphragm should not be used as a means of reducing the intensity of illumination because this reduces the NA of the condenser (see RESOLVING POWER). (See also ABBE CONDENSER; CRITICAL ILLUMINATION.) condensing enzyme Syn. citrate synthase (EC 4.1.3.7) [see Appendix II(a)]. conditional lethal mutant A mutant organism (e.g. a bacterium or virus) in which the mutation does not significantly affect the phenotype under one set of conditions (permissive conditions) but is lethal or inhibitory to the organism under another set of conditions (restrictive or non-permissive conditions). See e.g. TEMPERATURE-SENSITIVE MUTANT and HOST-DEPENDENT MUTANT. conduction (mol. biol.) See CONJUGATION (1b)(i). condyloma (pl. condylomas or condylomata) An elevated, wartlike lesion of the skin. Condyloma acuminatum = genital wart (see PAPILLOMA); condyloma latum = a wide, flat condyloma occurring chiefly in the anogenital region in secondary SYPHILIS. Condylostoma See HETEROTRICHIDA. confluent growth See CULTURE. confocal scanning light microscopy (CSLM) A form of light MICROSCOPY in which linear resolution is superior to that obtainable with conventional light microscopes. Essentially, rays from a laser-illuminated pin-hole are focused in the plane of the specimen and collected by a lens system which rapidly scans the specimen in synchrony with the illuminating source. As the optical system scans the specimen the rays entering the collector lens are continually modulated by the specimen; the modulated rays are focused onto a detector plate – generating a signal which modulates a cathode ray tube and forms a visual display of the image. congeneric Of the same genus. congenital Present at birth. conglutinated ‘Glued together’ – used e.g. of hyphae in certain prosenchymatous fungal or lichen tissues. conglutination See CONGLUTININ. conglutinin A protein, present in normal bovine serum, which can bind to a cleavage product of complement component C3b (see COMPLEMENT FIXATION); conglutinin can agglutinate particles/cells to which the cleavage product has adhered – a phenomenon termed conglutination. conglutinogen Potential activity associated with complement component C3b; cleavage of C3b by FACTOR I exposes a site which can bind CONGLUTININ. conglutinogen-activating factor Syn. FACTOR I. Congo–Crimean haemorrhagic fever See VIRAL HAEMORRHAGIC FEVERS. Congo red A red acid diazo DYE used e.g. as a PH INDICATOR (pH 3.0–4.5, blue to red) and for staining b-linked fibrillar polysaccharides (e.g. cellulose); Congo red disrupts CELLULOSE and CHITIN microfibril formation in growing cells (cf. CALCOFLUOR WHITE). conidia Plural of CONIDIUM. conidial head (mycol.) The expanded terminal portion of the conidiophore in certain fungi – see e.g. ASPERGILLUS. conidiation The phenomenon in which conidia function as gametes. Conidiobolus See ENTOMOPHTHORALES. conidiogenesis See CONIDIUM. 189

Coniocybe TRANSPOSON-mediated conjugation is considered separately in the entry CONJUGATIVE TRANSPOSITION. Any of various plasmid-borne genes (and, in some cases, chromosomal genes) may be transferred during conjugation; such genes include those conferring resistance to antibiotic(s). Conjugation occurs in both Gram-positive and Gram-negative bacteria; however, as the process differs in Gram-positive and Gram-negative species it is discussed under separate headings for the two categories. (i) Conjugation in Gram-negative bacteria. Much of the information on this topic has derived from studies on the transfer of the F PLASMID (q.v.), and other IncF plasmids, between strains of Escherichia coli ; the following account is based largely on this information. It is important to note that the general features of the F plasmid–E. coli transfer system are not common to all transfer systems found in Gram-negative bacteria. The stages of conjugation are outlined below, in sequence, on the basis of current models and data. Initial cell–cell contact. The presence of a (plasmid-encoded) pilus (see PILI) is believed to be essential for the donor phenotype. Moreover, different types of pilus mediate conjugation under different physical conditions, and they may function in different ways; for example, some types of pilus mediate conjugation only on moist (but not submerged) solid surfaces (e.g. agar plates), while others mediate conjugation either within the liquid phase or on a solid surface (see PILI) [see also Book ref. 177, pp 33–59 (42–45)]. In the F plasmid–E. coli conjugal system, initial donor–recipient contact is believed to occur when the tip of the pilus binds to a site on the surface of the recipient; the pilus is then believed to retract so that the cells achieve wall-to-wall contact. Stable cell–cell contact, involving specific plasmid-encoded proteins, is established after an initial period of unstable contact (during which donor and recipient are easily separated by mild shearing forces). (Mutant E. coli recipients defective in the OmpA protein (see OMP) form unstable contacts with donor cells, although this deficiency may be overcome by mating on a moist solid surface.) (See also SURFACE EXCLUSION.) An understanding of the initial donor–recipient interaction would require a detailed knowledge of the structure and mode of action of the pilus – from initial contact to the putative retraction. This information is currently unavailable; indeed, the conjugal transfer of DNA, even in the well-studied F plasmid–E. coli system, and particularly in the initial stages of cell–cell contact, has been described as a ‘black box’ [Mol. Microbiol. (1997) 23 423–429]. Some authors report that the region of contact between donor and recipient is characterized by a specific, electron-dense conjugational junction [JSB (1991) 107 146–156; JB (2000) 182 2709–2715]. The composition of this electron-dense layer is unknown but one suggestion is that, in F plasmid-mediated matings, it may consist of, or contain, F-pilin (the subunit of the F pilus) [Mol. Microbiol. (1997) 23 423–429]; however, results from recent studies on RP4-mediated matings indicated that conjugational junctions are not composed of pilin [JB (2000) 182 2709–2715]. On establishment of effective cell–cell contact, a ‘mating signal’ (nature unknown) promotes the mobilization of donor DNA. Mobilization and transfer of DNA. Mobilization is the process in which (in at least some cases, including the F plasmid) a single, specific strand of donor DNA is prepared for transfer to the recipient.

Annellidic development occurs e.g. in Scopulariopsis. (See also PERCURRENT PROLIFERATION.) (c) Phialidic development is very similar to annellidic development, the essential difference being that, in phialidic development, successive septa are formed at or near the level of the rim of the old wall; annellations are therefore not formed, although the edges of successive wall layers in the conidiogenous cell (phialide) may be visible just within the apical rim (collarette) formed by the original wall of the conidiogenous cell. Phialidic development occurs e.g. in Phialophora and Trichoderma. (d) Retrogressive development is similar to annellidic and phialidic development but differs in that each blastoconidium formed takes with it, on secession, a part of the original cell wall of the conidiogenous cell; the conidiogenous cell thus progressively shortens. It occurs e.g. in Cladobotryum. (e) Tretic (porogenous) development. The wall of the conidiogenous cell contains a narrow pore or channel; materials for conidial growth pass through this channel during the formation of the blastoconidia (‘poroconidia’ or ‘porospores’) – which arise either solitarily or in acropetally formed chains. Tretic development occurs e.g. in Alternaria. [Reviews: MS (1984) 1 86–89 and MR (1986) 50 95–132.] Conidiophores may arise individually or in discrete masses: see e.g. ACERVULUS, COREMIUM, PYCNIDIUM and SYNNEMA. Coniocybe See CALICIALES. Coniophora A genus of fungi of the APHYLLOPHORALES (family Coniophoraceae). C. puteana (= C. cerebella, ‘cellar fungus’), a cause of WET ROT, forms a thin, resupinate fruiting body which is initially cream-coloured but later olivaceous; the basidiospores are brownish. (See also CELLULASES.) Coniophoraceae See APHYLLOPHORALES. coniosporiosis Syn. MAPLE BARK STRIPPERS’ DISEASE. Coniothyrium See SPHAEROPSIDALES. conjugate (1) (verb) Carry out CONJUGATION (sense 1). (2) (noun) See CONJUGATION (sense 2). conjugate division See CLAMP CONNECTION. conjugate vaccine A VACCINE containing a polysaccharide antigen linked (conjugated) to a protein; such vaccines are useful for young children whose immune system does not respond adequately to (unconjugated) polysaccharide antigens. Some diseases are caused by pathogens with polysaccharide capsules, and conjugate vaccines containing such polysaccharides can elicit protective antibodies in young children. For example, a conjugate vaccine is used against diseases (epiglottitis, meningitis etc.) caused by Haemophilus influenzae type b [RMM (1996) 7 231–241]. [Responsiveness of infants to capsular polysaccharides: RMM (1996) 7 3–12.] [Vaccine against group B streptococci IV and VII: JID (2002) 186 123–126. Meningococcal C vaccine (in teenagers): Lancet (2003) 361 675–676.] conjugation (1) (‘mating’) Any of various processes in which gene transfer (or, exceptionally, complete fusion) follows the establishment of direct contact between two or more microbial cells (which may exhibit little or no morphological differentiation in comparison to vegetative cells). (a) (algol.) Conjugation occurs in several groups of algae (e.g. DESMIDS, certain DIATOMS, SPIROGYRA) and generally involves cell–cell contact followed by protoplast fusion. (b) (bacteriol.) In bacterial conjugation, DNA is transferred from a ‘male’ (donor ) bacterium to a ‘female’ (recipient) bacterium while the cells are in physical contact; a recipient which has received DNA from a donor is called a transconjugant. (cf. RETROTRANSFER.) The donor phenotype is commonly conferred on a cell by the intracellular presence of a CONJUGATIVE PLASMID (sense 1); 190

conjugation When chromosomal genes have been conjugally transferred (following mobilization of the chromosome), recombination between donor and recipient DNA appears to involve the RECBC PATHWAY. DNA synthesis in the donor cell. In the donor cell a complementary strand is synthesized on the non-transmitted strand in order to reconstitute the dsDNA plasmid; this synthesis, carried out by DNA polymerase III, is referred to as donor conjugal DNA synthesis (DCDS). DCDS is generally believed to be carried out by the ROLLING CIRCLE MECHANISM (although earlier claims that primers are needed for DCDS had made this uncertain). More recently, a study using recombinant plasmids containing two tandemly repeated R64 oriT sequences (one initiation-proficient but termination-deficient, the other initiation-deficient but termination-proficient) has provided evidence of rolling circle synthesis [JB (2000) 182 3191–3196]. [DNA processing reactions in bacterial conjugation: ARB (1995) 64 141–169.] Mobilization of non-conjugative plasmids. The term ‘mobilization’ commonly includes instances in which (a) a nonconjugative plasmid (or part of the bacterial chromosome) is conjugally transferred by becoming covalently linked to a conjugative plasmid (transfer being initiated at oriT in the conjugative plasmid), or (b) a non-conjugative plasmid is conjugally transferred independently of (that is, without covalent linkage to) a conjugative plasmid by means of cell–cell contacts established by the conjugative plasmid; mobilization of the latter type does not necessarily involve co-transfer (i.e. concomitant transfer) of the conjugative plasmid. (Some authors [ARG (1979) 13 99–125 (106)] have referred to (a) and (b) as conduction and donation, respectively.) (See also HFR DONOR and INTERRUPTED MATING.) The F plasmid can mobilize certain non-conjugative plasmids, e.g. the COLE1 PLASMID, in a way that does not require covalent linkage. Plasmid ColE1 is associated with a relaxosome which can be activated to promote mobilization and transfer of plasmid DNA; the in vivo mechanism of activation is unknown. During F-mediated mobilization and transfer of ColE1, one of the proteins of the relaxosome apparently remains covalently bound to the 5′ end of the transferred strand, and it has been suggested that this protein may act as a ‘pilot protein’, interacting with membrane protein(s) and guiding the 5′ terminal into the recipient. Mobilization of the non-conjugative plasmid R1162 involves at least four trans-acting plasmid-encoded products and a cisacting site (oriT), oriT being distinct from oriV [JB (1986) 167 703–710]. Effects of physicochemical parameters on conjugation. Relatively few studies have been carried out on the effects of variation in the physicochemical conditions under which cell–cell contact occurs. However, a number of early studies were conducted on the effects of variation in basic parameters such as pH, temperature, electrolyte concentration and osmotic pressure; one purpose of these studies was to characterize the response of the conjugal process to changes in ‘external’ conditions, thus obtaining data potentially useful e.g. for optimizing transfer in the laboratory. These studies found e.g. that transfer of the IncFII plasmid R1drd19 could be greatly stimulated by higher levels of electrolyte [FEMS (1983) 20 151–153]; that the plasmid could be transferred between 37 and 17° C [AEM (1981) 42 789–791]; that the effects of non-optimal pH and non-optimal temperature are synergistic [AEM (1983) 46 291–292]; that transfer is subject to osmotic constraint [FEMS (1984) 25 37–39]; and

In the F plasmid, an essential prerequisite for mobilization is the formation of a NICK at a specific site (designated nic), in a specific strand, within the origin of transfer (oriT); nicking occurs in that strand which is to be transferred to the recipient (the T-strand). Nicking is mediated by an endonuclease (a relaxase) that forms part of a so-called relaxosome (previously called a relaxation complex). The relaxosome associated with the F plasmid is a nucleoprotein complex consisting of the transfer origin (oriT), the relaxase, and certain other proteins. (Relaxases are encoded e.g. by the F plasmid traI gene, the traI gene of plasmid RP4, and the nikA gene of Salmonella plasmid R64.) As well as endonuclease activity, the TraI protein of the F plasmid also has (ATP-dependent) helicase activity and is referred to as helicase I. Components of the relaxosome are assembled in a specific order: TraI binds after the INTEGRATION HOST FACTOR and the TraY protein [JBC (1995) 270 28381–28386]. Recent studies confirm that TraY is required for in vivo nicking [JB (2000) 182 4022–4027]. The relaxase is believed to mediate an ongoing cycle of nicking and ligation at the nic site, i.e. nicking appears not to be triggered by donor–recipient contact. Following the mating signal in F plasmid–E. coli systems, it appears that the nicked strand enters the recipient in the 5′ -to′ 3 direction. (Single-strand transfer in the 5′ -to-3′ direction is believed to occur in at least some other cases.) Transfer of the nicked strand from donor to recipient requires that the strand be unwound from its complementary strand, and this is thought to involve helicase I (TraI); if helicase I is involved, and if it is immobilized in relation to the cell envelope, then the unwinding of the transferred strand may provide energy for strand transfer. One early study indicated that the transferred strand could pass through an extended pilus to the recipient [JB (1990) 172 7263–7264]. A later study – which used video-enhanced lightmicroscopy and electron microscopy – concluded that DNA is transferred while donor and recipient are in close wall-to-wall contact [JSB (1991) 107 146–156]. The precise mode of transfer of DNA from donor to recipient is not known. For F plasmid-mediated systems, it has been postulated that the relaxosome may be coupled, via TraD, to a transport apparatus (transferosome) consisting of a protein complex located in the cell envelope at the base of the pilus. In RP4-mediated mating, the transfer apparatus in the donor may include a structure that bridges the cytoplasmic and outer membranes [JB (2000) 182 1564–1574], although this was not detected in another study on RP4-mediated mating [JB (2000) 182 2709–2715]. DNA synthesis in the recipient cell. When a cell receives the transmitted strand of an F plasmid, a complementary strand is synthesized to form a circularized dsDNA molecule; this recA-independent process is called repliconation. Complementary strand synthesis apparently involves the recipient’s DNA polymerase III and other host-encoded enzymes. For certain IncI and IncP plasmids (e.g. ColIb, RP4), synthesis of DNA in the recipient is initiated by a donor-plasmid-encoded PRIMASE, i.e. during conjugation, primase, as well as ssDNA, is transferred from donor to recipient. In such cases, DNA synthesis is initiated from primers which are formed at various locations on the transferred strand. [Plasmid DNA primases in conjugation: Book ref. 161, pp 585–603.] Matings with ColIb-P9 involve the transfer, from donor to recipient, of molecules which include the product of the sog gene, which has primase activity [EMBO (1986) 5 3007–3012]. 191

conjugational junction that transfer is inhibited by particles of colloidal clay [AEM (1983) 46 756–757]. Transfer of the IncN plasmid R269N1, which mediates surface-obligatory mating (see PILI), appears to need, or be assisted by, surface tension [FEMS (1983) 19 179–182; JGM (1983) 129 3697–3699]. Some early experiments [e.g. JGM (1987) 133 3099–3107] purported to demonstrate the possibility of plasmid transfer in natural aquatic environments but were flawed by extreme artificiality. (ii) Conjugation in Gram-positive bacteria. Conjugal transfer is known to occur in organisms from various genera, including Bacillus, Enterococcus, Lactococcus, Staphylococcus and Streptomyces. As in conjugation in Gram-negative bacteria, some plasmids can be transferred across a broad host range; for example, plasmid pAMb1 , which encodes resistance to erythromycin, can be transferred from streptococci to e.g. Bacillus subtilis and Lactobacillus casei. There are two main types of plasmid-mediated conjugation in Gram-positive species: PHEROMONE-mediated and (apparently) pheromone-independent mating; pili have not been demonstrated in either category. Pheromone-mediated conjugation in e.g. strains of Enterococcus faecalis (see PHEROMONE) occurs in liquid (broth) cultures, and the plasmids involved commonly contain genes conferring resistance to antibiotics. Some of these plasmids also encode a peptide which antagonizes the corresponding pheromone; such a peptide may have the function of ensuring that a mating response in the donor cell is not triggered unless the relevant pheromone is in a sufficiently high concentration, i.e. conditions under which there is a good chance of a random collision between donor and recipient cells. [Review: JB (1995) 177 871–876.] Pheromone-independent conjugation requires that the donor and recipient be present on a solid surface (e.g. a nitrocellulose filter) – rather than in a liquid medium. Conjugation of this type occurs e.g. in strains of Staphylococcus and Streptococcus. The plasmids, which encode e.g. resistance to antibiotics, are commonly >15 kb in size. In Bacillus subtilis, recombinants may be obtained by coincubation of two apparently plasmid-less parent strains for extended periods of time (e.g. 20 hours); in such crosses most exconjugants contain the entire genome of both parent strains, and the process is believed to resemble a form of temporary cell fusion [Book ref. 199, pp 25–39]. (cf. PROTOPLAST FUSION.) As in Gram-negative bacteria, certain plasmids may be mobilized by other plasmids, and some of the small multicopy plasmids encode function(s) which specifically promote their own mobilization. Mobilization of the streptococcal plasmid pMV158 has been studied in Escherichia coli using R388 or RP4 as the auxiliary plasmid [Microbiology (2000) 146 2259–2265]. (c) (ciliate protozool.) Conjugation occurs in many ciliates; it involves either the temporary association of two individual cells (as e.g. in Paramecium or Tetrahymena) or the complete fusion of conjugal partners (as e.g. in peritrichs). In some ciliates (e.g. Blepharisma) conjugation is promoted by soluble substances (see GAMONE) which are released by the cells; in other ciliates (e.g. Paramecium) the chemical signals remain bound to the cell. In Paramecium aurelia, two individuals of appropriate mating type (see SYNGEN) pair with their ventral surfaces in contact, and an intercellular cytoplasmic bridge forms in the cytostomal region. In each conjugant (i.e. partner) the MACRONUCLEUS disintegrates, and both of the micronuclei (see MICRONUCLEUS) undergo meiosis to form eight haploid pronuclei; seven pronuclei disintegrate. (In Paramecium caudatum the fate of a given

pronucleus depends on its position within the cytoplasm; the nucleus which survives is located in the cytostomal region [JCS (1985) 79 237–246].) The surviving pronucleus (= gonal nucleus) divides mitotically to form a pair of gametic nuclei, one of which passes to the conjugal partner and fuses with the stationary nucleus to form a zygotic nucleus (= synkaryon). Subsequently, mitotic divisions of each synkaryon lead to the formation of four diploid nuclei in each conjugant – the conjugants by now having separated; two of the nuclei give rise to two new micronuclei, while the other two form two new macronuclei. During the first binary fission after conjugation, the micronuclei (but not the macronuclei) undergo mitotic division; each daughter cell receives one macronucleus and two micronuclei – thus restoring the normal nuclear constitution of the species. In P. aurelia conjugation takes ca. 12–18 hours. [DNA synthesis, methylation and degradation during conjugation in Tetrahymena thermophila: NAR (1985) 13 73–87.] In peritrichs, two morphologically dissimilar conjugants are formed: a female macroconjugant and a smaller, motile, ciliated microconjugant which swims in search of, and fuses with, a macroconjugant. (See also AUTOGAMY and CYTOGAMY.) (d) (mycol.) See e.g. MATING TYPE and PHEROMONE. (2) (immunol.) The process of covalently linking two or more species of molecule to form a hybrid molecule (a conjugate); for example, a dye may be linked to a protein (as in fluoresceinconjugated antiglobulin), or glutaraldehyde may be used to link two different antibodies to form a hybrid antibody [SAB (1984) 22 73–78]. (See also CONJUGATE VACCINE.) conjugational junction See CONJUGATION (1b)(i). conjugative pili See PILI. conjugative plasmid (1) (self-transmissible plasmid) As commonly used: a PLASMID which encodes all the functions needed for its own intercellular transmission by CONJUGATION (sense 1b); in e.g. the F PLASMID (q.v.) these functions include pilus formation (see PILI) and the formation of proteins involved in the initial preparation of plasmid DNA for transfer. Such a plasmid may also bring about the mobilization of a (mobilizable) NON-CONJUGATIVE PLASMID or the mobilization of the donor’s chromosome. (cf. SEX FACTOR; see also ANDROPHAGE and PROMISCUOUS PLASMIDS.) (2) According to some authors [ARG (1979) 13 99–125 (105–106)]: a plasmid which encodes e.g. pilus formation but which may or may not be capable of mobilization; only if such a plasmid is mobilizable is it self-transmissible. conjugative transposition In bacteria: CONJUGATION mediated by a conjugative transposon, i.e. independently of a conjugative plasmid, the transposon being transferred from the donor cell to the recipient cell. First reported in Gram-positive bacteria, it is now well established in Gram-negatives (e.g. Bacteroides); indeed, it may permit gene transfer between Gram-positives and Gram-negatives [e.g. AEM (2001) 67 561–568; AEM (2003) 69 4595–4603]. A model for Gram-positive conjugative transposition was as follows. Contact between donor and recipient triggers excision of the transposon in the donor, this involving a transposon-encoded recombinase (product of gene int). Each end of the excised transposon carries single-stranded host DNA called a coupling sequence. The excised transposon then circularizes through basepairing (albeit mis-matched) between coupling sequences. A single strand may be transferred to the recipient, the complementary strand being synthesized in the recipient prior to insertion. Insertion of the (double-stranded) transposon into the target site is neither 192

contagious equine metritis consortium A more or less stable physical association between the cells of two or more types of microorganism – advantageous to at least one of the organisms; SYNTROPHISM seems to characterize many (perhaps all) consortia. One example is CHLOROCHROMATIUM AGGREGATUM. [Review: ME (1996) 31 225–247.] conspecific Of the same species. constant region (of Ig) See IMMUNOGLOBULINS. constitutive Refers either to a gene which is expressed constantly, or to the product of such a gene. The level of expression of a constitutive gene depends largely on the efficiency of its PROMOTER. constitutive heterochromatin See CHROMATIN. consumption Pulmonary TUBERCULOSIS. consumption test (serol.) Any test in which a measurement is made of the amount of antibody or antigen which is used up (consumed) by antigen–antibody combination in a test system; the amount consumed is determined by titrating the residual (unconsumed) antibody or antigen and comparing it with the quantity initially present. (See e.g. ANTIGLOBULIN CONSUMPTION TEST.) contact biotrophic mycoparasite A fungus which parasitizes other fungi by means of specialized cells which make contact with – but do not penetrate or cause obvious damage to – mycelium of the (living) host; most of the known species (including e.g. Calcarisporium parasiticum) require biotin, thiamine, and an unidentified substance, ‘mycotrophein’, for growth. (See also MYCOPARASITE.) contact-dependent secretion See type III systems in PROTEIN SECRETION. contact dermatitis Syn. CONTACT SENSITIVITY. contact inhibition See transformation in TISSUE CULTURE. contact sensitivity (contact dermatitis) A form of DELAYED HYPERSENSITIVITY in which the subject is primed by cutaneous exposure to certain protein-binding substances – e.g. dinitrofluorobenzene, certain metals (e.g. nickel) and antibiotics (e.g. neomycin) – which bind skin proteins to form neoantigens; subsequent challenge, after ca. 1 week, with the sensitizing substance results in a typical lesion in 24–48 hours. (See also LANGERHANS’ CELLS.) contagious abortion See BRUCELLOSIS. contagious acne Syn. CONTAGIOUS PUSTULAR DERMATITIS (2). contagious bovine pleuropneumonia In cattle: acute lobar PNEUMONIA, with pleuritis, caused by a strain of Mycoplasma mycoides; infection occurs mainly by droplet inhalation. Incubation period: 3–6 weeks (sometimes longer). Onset is sudden, with fever and anorexia; subsequently there is a deep cough and dyspnoea. Death from anoxia may occur within days or weeks (mortality rate up to ca. 50%); survivors may become asymptomatic carriers. Treatment: antibiotic and/or other therapy is generally given only where the disease is enzootic. (See also BOVINE RESPIRATORY DISEASE.) contagious disease (1) Syn. INFECTIOUS DISEASE. (2) A disease normally transmissible only by direct physical contact between infected and uninfected individuals – as e.g. in many VENEREAL DISEASES. contagious ecthyma Syn. CONTAGIOUS PUSTULAR DERMATITIS (1). contagious equine metritis (CEM) A sexually transmitted HORSE DISEASE (first recognized in Suffolk, UK, in 1977) characterized by endometritis with mucopurulent vulval discharge and temporary infertility; clinical symptoms usually resolve rapidly. A symptomless carrier state occurs in both mares and stallions. The causal agent is a previously unknown bacterial species. It is a Gram-negative coccobacillus (occasionally filamentous); catalase +ve; oxidase +ve; asaccharolytic; gives −ve reactions in

site-specific nor random; each target site seems to contain an A-rich sequence of nucleotides and a T-rich sequence, the two sequences being separated by about six nucleotides. In Bacteroides (Gram-negative) excision and transfer of the conjugative transposon CTnDOT (which is found in many strains of Bacteroides) is governed by an OPERON that may be regulated by a TRANSLATIONAL ATTENUATION mechanism [JB (2004) 186 2548–2557]. A recipient which has received a conjugative transposon is a transconjugant; receipt confers the donor phenotype. (Interestingly, strains of Lactobacillus lactis can receive conjugative transposons but, apparently through lack of particular host function(s), transposons cannot be excised – so that L. lactis cannot act as a donor.) Characteristically, conjugative transposons are resistant to restriction. It may be relevant that the orf18 gene in Tn916 has been found to encode a product similar to the antirestriction proteins encoded by some plasmids. All conjugative transposons from pathogenic bacteria carry the tetracycline-resistance tet(M) gene [mechanism of Tet(M): JB (1993) 175 7209–7215], and some carry other types of antibiotic-resistance gene(s). These transposons are mobile among a wide range of host species, and are often responsible for antibiotic resistance in plasmid-less Gram-positive pathogens; they have been identified in e.g. Enterococcus faecalis, E. faecium and Streptococcus pneumoniae. Conjugative transposons occur in e.g. plasmids and chromosomes, and range in size from about 18 kb (Tn916 ) to >50 kb; some of the larger ones (e.g. Tn5253 ) apparently consist of a Tn916-like entity within another transposon (each being able to transpose independently). Conjugative transposons include Tn916, Tn925, Tn1545, Tn3710 and Tn5253. They differ from the ‘classical’ transposons in several ways: (i) they mediate conjugation; (ii) when they insert, they do not duplicate the target site; (iii) when excised, the transposon forms a cccDNA intermediate; (iv) the recipient duplex is characteristically in another cell. conjunctivitis Inflammation of the conjunctivae. It may be due e.g. to physical or chemical irritation, allergic reaction, or to infection by bacteria (e.g. Haemophilus influenzae, Moraxella lacunata) or viruses (e.g. adenoviruses). (See e.g. ACUTE HAEMORRHAGIC CONJUNCTIVITIS; EPIDEMIC KERATOCONJUNCTIVITIS; GONORRHOEA; INCLUSION CONJUNCTIVITIS; PHARYNGOCONJUNCTIVAL FEVER; PINK-EYE; TRACHOMA.) conk A colloquial name for the fruiting body of a wood-rotting basidiomycete (particularly a polypore). Conocybe See AGARICALES (Bolbitiaceae). conocyst An EXTRUSOME of the gymnostome Loxophyllum. conoid A hollow cone of spirally arranged fibrils or tubules, open at the apex, found at the extreme anterior end in certain members of the APICOMPLEXA; it may assist in the penetration of the host cell. consensus sequence (mol. biol.) Of the variant forms of a given type of genetic element (e.g. a PROMOTER): a theoretical ‘representative’ nucleotide sequence in which each nucleotide is the one which occurs most often at that site in the various forms of the genetic element which occur in nature. The phrase is also used to refer to an actual sequence which approximates the theoretical consensus. conserved name In NOMENCLATURE: a name retained (by a recognized taxonomic body) even though it may contravene rule(s) of the relevant code. consolidation (med.) See e.g. PNEUMONIA (a). 193

contagious hypovirulence most biochemical tests; grows slowly e.g. on chocolate agar at 37° C (optimum temperature); GC%: 36.1. [Book ref. 181, pp. 49–96.] contagious hypovirulence See HYPOVIRULENCE. contagious pustular dermatitis (1) (orf; contagious ecthyma; scabby mouth) A disease which affects mainly sheep (especially lambs) – in which pustular, scab-forming lesions form on the lips and face and in the mouth; the causal agent, a PARAPOXVIRUS, is presumed to infect via abrasions. Morbidity may be high, but mortality rates are generally very low. In cattle, lesions may be formed on the teats. In man, the disease is localized and selflimiting, involving the formation of lesions e.g. on the hands, arms or eyelids. (2) (syn. contagious acne) A HORSE DISEASE characterized by the formation of pustules, particularly where the skin is in contact with harness; causal agent: Corynebacterium pseudotuberculosis. contaminative infection (1) (parasitol.) Infection by pathogens derived from the POSTERIOR STATION of the vector. (cf. INOCULATIVE INFECTION.) (2) Infection brought about by the ingestion of material containing pathogens. context (mycol.) In basidiomycetes: the sterile (i.e., nongenerative) structural tissue which forms the main bulk of a fruiting body, particularly that of the pileus. (cf. TRAMA.) continuous cell line Syn. ESTABLISHED CELL LINE. continuous centrifugation See CENTRIFUGATION. continuous cooker–cooler See COOKER–COOLER. continuous cultivation Syn. CONTINUOUS CULTURE. continuous culture (continuous-flow culture; continuous cultivation; open culture; open-system culture) The culture of microorganisms, in a liquid medium, such that the organisms can exhibit continual exponential or near-exponential growth (balanced GROWTH) for an extended period of time. (cf. BATCH CULTURE.) Essentially, the procedure involves a continual inflow of fresh medium to the culture (with which it is well mixed) and the simultaneous outflow of an equal volume of fluid consisting of a mixture of old and fresh medium and a proportion of biomass; under ‘steady-state’ conditions the concentration of biomass in the culture vessel remains constant. In continuous culture, growth can occur, ideally, under defined and effectively invariant conditions; for this reason continuous culture is used e.g. for studies of microbial metabolism: data from continuous culture are generally more reproducible than are those from batch culture. The commonest forms of apparatus used in continuous culture are the chemostat and the turbidostat (see also GRADOSTAT). In the chemostat a culture normally grows at a sub-maximal growth rate, and a steady state (at a given growth rate) is achieved by controlling the concentration (always at growthlimiting levels) of an essential substrate in the incoming medium (and, hence, in the culture vessel). (By using very low concentrations of a given essential substrate it is possible to achieve very low rates of growth – similar to those believed to occur e.g. in certain aquatic habitats.) Under steady-state conditions, the growth rate and the concentration of the growth-limiting substrate often have the relationship predicted by the Monod equation (see SPECIFIC GROWTH RATE), and the specific growth rate is numerically equal to the DILUTION RATE. Under steadystate conditions the concentration of biomass in the chemostat is governed by the rate at which the growth-limiting substrate is supplied to the culture, and (for a given rate of supply of that substrate) the concentration of biomass cannot be varied by the operator. (See also YIELD COEFFICIENT.) The conditions

in a chemostat tend to be unstable at or near the maximum growth rate. In the turbidostat a culture normally grows at or near the maximum growth rate, and all substrates are usually present in excess; within certain limits, the concentration of biomass in the turbidostat can be selected by the operator, and a steady state is achieved by adjusting the dilution rate such that cell growth is matched by the rate of loss of cells from the culture vessel. Control of culture density (i.e. number of cells per unit volume) may be achieved e.g. by a photosensitive device which monitors the opacity of the culture and automatically adjusts the flow rate; however, this method may suffer from inaccuracies due e.g. to foaming and to ‘wall growth’ (see later). Alternatively, culture density can be controlled by monitoring other parameters which are closely linked to specific growth rate – e.g. pH (in a ‘pH-stat’), CO2 evolution (in a ‘CO2 -stat’), or oxygen uptake. In continuous culture, deviations from ideal (predictable) operation are common. Such deviations may arise e.g. as a result of the inability to achieve perfect (100%, instantaneous) mixing of the inflowing medium with the culture fluid; imperfect mixing may be indicated by a stable dilution rate which exceeds Dc . Changes in the rate of agitation can affect the mean cell volume of the cultured cells [JGM (1985) 131 725–736]. Wall growth (adherence to, and growth of, the cultured cells on the walls of the culture vessel) may give an effect similar to (but usually greater than) that of imperfect mixing. Another type of deviation may occur when cells are cultured at low rates of growth; for example, under carbon-limited conditions a major part of the carbon source may be used to provide MAINTENANCE ENERGY (thus giving a lower-than-predicted yield of biomass), while under carbon-excess conditions the yield of biomass may be greater than predicted owing to the accumulation of intracellular reserve polymers (e.g. PHB). A different type of problem involves the emergence of mutants during the (extended) periods of culture – an effect which can change the character of the biomass if particular mutant(s) can outgrow the parent strain; nevertheless, it is possible to take advantage of this effect – e.g. when it is desired to isolate mutants which synthesize more (or more effective) enzyme(s) or which can take up the growthlimiting substrate more efficiently than can the parent strain. continuous-flow culture Syn. CONTINUOUS CULTURE. continuum model See CELL CYCLE. Contophora Algae except members of the RHODOPHYTA. (cf. ACONTA.) contour-clamped homogeneous electric field electrophoresis (CHEF) See PFGE. contractile vacuole An osmoregulatory organelle, one or more of which may occur in the cytoplasm in most freshwater (and some saltwater) eukaryotic microorganisms (cf. PUSULE); basically, it is a membrane-limited region which, under normal environmental conditions, alternately fills with fluid (diastole) and then discharges the fluid to the exterior (systole). During diastole, the contractile vacuole may be fed by a surrounding layer of small vesicles which appear to coalesce with the main vacuole (as in amoebae), and/or – depending on species – it may be fed by a system of collecting tubules which ramify in the cytoplasm (forming the spongiome, = spongioplasm, = ‘nephridial network’) and apparently drain areas remote from the vacuole (a system characteristic of ciliates). In some protozoa (e.g. Paramecium, Tetrahymena) discharge occurs at a fixed site (pore) in the pellicle. The mechanism of contractile vacuole activity is not known. Systole may involve cytoplasmic turgor pressure; at least in 194

copy number ciliates, the vacuole wall may be inherently contractile. In general, the length of the diastole–systole cycle (seconds, minutes or hours) appears to depend on temperature, on the size of the cell (being shorter in smaller cells), and on the osmolarity of the medium. [Review: Biol. Rev. (1980) 55 1–46.] convalescent serum SERUM from a patient in the convalescent stage of a disease; in some cases it may be used to provide PASSIVE IMMUNITY. convergent trama See BILATERAL TRAMA. Convoluta A genus of flatworms (platyhelminths), found on sandy sea shores in the intertidal zone, which form a symbiotic association with certain unicellular green algae. On hatching, the young flatworms ingest cells of TETRASELMIS; the algal cells lose their flagella, theca and eyespot, and reside between the cells of the subepidermal tissues in the flatworm where they continue to photosynthesize. The flatworm eventually ceases to feed, its digestive organs degenerate, and it becomes completely dependent on the photosynthate produced by Tetraselmis. Eventually, the algal cells themselves are digested, and the animal then dies. (cf. ELYSIA; see also ZOOCHLORELLAE.) cooked meat medium (chopped meat medium; Robertson’s cooked meat medium) Any of a range of media containing boiled, de-fatted, minced lean beef, and used e.g. for the growth of ANAEROBES, for the sporulation of clostridia, and as maintenance media for e.g. clostridia and streptococci; in some formulations the medium incorporates a reducing agent (e.g. L-cysteine or thioglycollate) and e.g. haemin, vitamin K1 and yeast extract. The medium is sterilized by autoclaving, and the final pH is about 7.4; it is stored in screw-cap bottles, and is sometimes equilibrated under O2 -free conditions at room temperature before the cap is tightened. [Recipe: (e.g.) Book Ref. 53, pp. 1423–1424.] cooker–cooler (continuous cooker–cooler) In CANNING: a vessel within which filled, sealed cans (or other containers) undergo heat treatment in a continuous-type process (cf. BATCH RETORT). In rotary-type cooker–coolers, the cans enter and leave, through self-sealing valves, a chamber containing steam under pressure. In hydrostatic-type cooker–coolers, pressure in the steam chamber supports vertical columns of water through which the cans enter and leave the chamber. cooking (industrial microbiol.) (1) In the food processing industry: heat treatment used for APPERTIZATION. (See also c0 .) (2) A stage in CHEESE-MAKING. Coomassie brilliant blue A sensitive stain for proteins. The red (anionic) form of the dye becomes blue when bound to protein amino groups. Coombs’ reagent (serol.) Syn. ANTIGLOBULIN. Coombs’ test (serol.) Syn. ANTIGLOBULIN TEST. Cooper–Helmstetter model Syn. HELMSTETTER–COOPER MODEL. cooperative binding A mode of binding (e.g. of protein molecules to a DNA strand) in which the binding of one molecule facilitates binding of the next. co-oxidation See CO-METABOLISM. cop gene A gene involved in the control of the COPY NUMBER of a plasmid. (See e.g. R1 PLASMID.) cophenetic correlation coefficient In NUMERICAL TAXONOMY: a measure of the accuracy with which a phenogram represents a given S matrix. copiotroph Any organism which grows only in the presence of high concentrations of nutrients. (cf. OLIGOTROPH.) copper (as an antimicrobial agent) Copper is a HEAVY METAL which is essential (in trace amounts) for the activity of a number of microbial proteins (e.g. cytochrome aa3 , tyrosinase).

However, in effective concentrations, copper and certain of its compounds are useful antimicrobial agents; toxicity to microorganisms appears to reside in the cupric ion. Copper sulphate has been used as an anti-algal agent in e.g. swimming pools and as a constituent of various agricultural antifungal agents (see e.g. BORDEAUX MIXTURE, BURGUNDY MIXTURE, CHESHUNT COMPOUND). Copper naphthenate is a greenish, waxy solid, soluble in various organic solvents, which is used as an antifungal preservative for e.g. cellulosic textiles. Copper soaps are copper salts of certain fatty or oleoresinous acids (e.g. copper stearate, copper tallate) which have antifungal activity similar to that of copper naphthenate. Cuprammonium hydroxide is used in aqueous solution for rot-proofing fabrics. Cupric ions are complexed by 8-HYDROXYQUINOLINE (one atom of copper to two molecules of 8-hydroxyquinoline) to form copper 8-quinolinolate (copper-oxine; copper oxinate) which is a highly effective antifungal agent used e.g. in agriculture and as a preservative for textiles. (Copper compounds are not used in rubber products since they catalyse the oxidation of rubber.) copper 8-quinolinolate See COPPER. copper soaps See COPPER. co-precipitation (serol.) The precipitation of otherwise nonprecipitating molecules etc. as part of, or enmeshed with, an immune complex. Coprinaceae See AGARICALES. Coprinus A genus of humicolous, lignicolous or coprophilous fungi (AGARICALES, Coprinaceae) in which, in most species, the lamellae undergo rapid autodigestion at maturity (see LAMELLA and BASIDIOSPORE). (See also INK-CAP FUNGI.) coproantibodies Antibodies produced by the intestinal mucosa and found in the lumen of the gut; they are mainly of the secretory IgA class. Coprococcus A genus of Gram-positive, asporogenous, anaerobic bacteria which occur e.g. in the human gut; the organisms ferment carbohydrates with the production of butyric and acetic acids. Cells: cocci, occuring in pairs or chains. GC%: ca. 39–42. coprogen See SIDEROPHORES. Copromyxa See ACRASIOMYCETES. Copromyxella See ACRASIOMYCETES. coprophilic (coprophilous) Refers to an organism which grows preferentially or exclusively on or in animal faeces. For example, certain fungi (e.g. species of Coprinus, Pilobolus and Sordaria) grow more or less specifically on dung – particularly that of herbivorous animals. co-protease (coprotease) A type of molecule which, acting nonenzymically, can promote autocatalytic cleavage of a protein; an example is RecA∗ in the SOS SYSTEM. coprozoic Refers to e.g. protozoa which are COPROPHILIC. copy-choice model See RECOMBINATION. copy-mutant (copy-number mutant; cop mutant) A mutant PLASMID whose COPY NUMBER differs from that of the wild-type plasmid. In copy mutants the copy number is usually higher than that of the wild-type plasmid, but in some cases it is lower. copy number (1) (of a bacterial plasmid) The number of copies of a given PLASMID, per chromosome, in a cell; copy number depends on the replication control system encoded by the plasmid, on the strain or species of cell in which the plasmid occurs, and on growth conditions. In plasmid-containing bacteria in the exponential phase of growth, a given plasmid occurs with a characteristic copy number; any perturbation in copy number tends to be corrected by a rise or fall in the frequency of plasmid replication. Mutations in a plasmid (and/or chromosome) may give rise to a COPY MUTANT. 195

CoQ Copy number is determined primarily by the regulation of initiation of plasmid replication; thus, e.g. a particular mutant of pBR322 (a plasmid related to the COLE1 PLASMID – q.v.) which encodes an altered (less effective) negative regulatory molecule (RNA I) exhibits an 8-fold increase in copy number [JGM (1986) 132 1021–1026]. Other factors which govern copy number include the PARTITION system (if any) of the plasmid. In some plasmids the ccd system contributes to the stability of plasmid inheritance (see F PLASMID). (See also INCOMPATIBILITY and MULTICOPY PLASMID.) (2) The number of copies of e.g. a given gene product per copy of that gene (or per cell), or the number of copies of a given gene per cell etc. CoQ Coenzyme Q: see QUINONES. coral fungi See APHYLLOPHORALES (Clavariaceae). coral spot See NECTRIA. coral symbiosis See ZOOXANTHELLAE. Corallina See RHODOPHYTA. Corallococcus See MYXOBACTERALES. Corallomyxa See ACARPOMYXEA. cord factor Any of the MYCOLIC ACID diesters of TREHALOSE found in the cell walls of Mycobacterium spp and in other mycolic acid-containing species. The name ‘cord factor’ was originally given to a glycolipid (6,6′ -dimycolyl-a,a′ -D-trehalose) derived from tubercle bacilli characterized by growth in the form of ‘cords’. Certain mycolic acid esters (e.g. 6,6′ -dimycolyla,a′ -D-trehalose, or 5-mycolyldiarabinoside) from the walls of M. tuberculosis can potentially act as ENDOTOXINS (sense 2) by uncoupling mitochondrial electron transport and oxidative phosphorylation [Ann. Mic. (1983) 134 B 233–239]. cordycepin (3′ -deoxyadenosine) An inhibitor of RNA synthesis; it is obtained e.g. from Cordyceps militaris. Cordyceps A genus of fungi (order CLAVICIPITALES) which include parasites of insects and of other fungi. At least some entomogenous species can form CHITINASES, and infection appears to be initiated via the cuticle and haemolymph rather than via the gut; the fungus subsequently forms, on the dead insect, an erect, cylindrical or clavate stroma which contains perithecia in the surface layer. The dead host is resistant to decay – apparently due to the presence of CORDYCEPIN. C. militaris (‘scarlet caterpillar fungus’) forms orange stromata (ca. 2–5 cm high) on the larvae and pupae of butterflies and moths. C. canadensis is parasitic on Elaphomyces spp. core (1) (virol.) Any of various internal structures within a virion – commonly a protein–nucleic acid complex; the core may be enclosed within a CAPSID (see e.g. HERPESVIRIDAE), a membrane (see e.g. POXVIRIDAE) or an ENVELOPE (see e.g. RETROVIRIDAE). (cf. NUCLEOCAPSID.) (2) (bacteriol.) See ENDOSPORE sense 1(a). core oligosaccharide See LIPOPOLYSACCHARIDE. core particle (of chromatin) See CHROMATIN. coremium In some fungi (e.g. Penicillium expansum): an erect bundle of spore-bearing hyphae, the hyphae being associated more loosely than those in a SYNNEMA. (For some authors the terms coremium and synnema are synonymous.) corepressor See OPERON. coriaceous Leathery in texture. Coriolus A genus of fungi of the APHYLLOPHORALES (family Polyporaceae) which form non-stipitate, typically semicircular, bracket-type basidiocarps on deciduous wood; the context is trimitic, usually leathery, rubbery or woody, and the hymenophore is porous. In C. versicolor (sometimes called Trametes versicolor ) the upper surface of the basidiocarp is often

velvety, exhibiting a number of dark bands concentric about the region of attachment, while the lower surface is pale; basidiospores: cream-coloured, ca. 6 × 2 µm. (See also WHITE ROT and LIGNIN.) corn oil test (for lipase) See LIPASE. corn stunt disease A leafhopper-transmitted YELLOWS disease of maize, characterized by stunting and leaf striping/discoloration, caused by the MAIZE CHLOROTIC DWARF VIRUS or by certain strains of Spiroplasma citri. [Proposal to regard the corn stunt spiroplasmas as a distinct species, S. kunkelii : IJSB (1986) 36 170–178.] cornmeal agar A mycological medium. Essentially, cornmeal (4% w/v) is heated in distilled water for 1 hour at 60–65° C; agar (1.5% w/v) is added to the filtrate, and the medium is autoclaved. Cornmeal agar is used e.g. to demonstrate chlamydospore formation in Candida albicans – which is reported to be encouraged by the addition to the medium of Tween 80. cornute Syn. ROESTELIOID. Coronaviridae A family of pleomorphic, enveloped, nonsegmented ssRNA viruses which infect man, animals or birds. One genus (Coronavirus) is currently recognized. Members include AVIAN INFECTIOUS BRONCHITIS virus (IBV; type species), human coronavirus (a causal agent of the COMMON COLD), murine hepatitis virus (MHV), porcine haemagglutinating encephalitis virus (see VOMITING AND WASTING DISEASE), and porcine TRANSMISSIBLE GASTROENTERITIS virus; probable members include e.g. coronavirus enteritis of turkeys virus (= turkey bluecomb disease virus), and neonatal calf diarrhoea coronavirus. ‘Possible members’ include feline infectious peritonitis virus (= feline coronavirus) and human enteric coronavirus (a possible causal agent of human FOOD POISONING). Virion: ca. 75–160 nm diam., consisting of a helical nucleocapsid surrounded by the envelope; characteristic club-shaped glycoprotein projections (peplomers, ‘spikes’) 12–24 nm long extend from the outer surface of the envelope. Genome: positivesense ssRNA, MWt typically ca. 6–7 × 106 (8 × 106 has been reported for IBV). The RNA is polyadenylated at the 3′ end. Proteins associated with the virion include (at least) S (‘spike’), M (membrane) and N (nucleocapsid). The virions are inactivated e.g. by lipid solvents and by detergents. Virus replication occurs in the host cell cytoplasm. In IBV, 6 subgenomic mRNAs (A–F) are formed, all of which are 3′ coterminal with the genomic RNA (a so-called ‘nested set’ of mRNAs); each 5′ end has a common leader sequence (ca. 70 bases long) derived from the 5′ end of genomic RNA [possible mechanism: JGV (1986) 67 221–228]. (MHV forms a ‘nested set’ of 7 subgenomic mRNAs, designated RNA1–RNA7.) The virions mature by budding through the endoplasmic reticulum into vesicles. [Molecular biology of coronaviruses: AVR (1983) 28 35– 112.] Coronavirus See CORONAVIRIDAE. Coronie wilt Syn. HARTROT. correction collar A part of a microscope objective lens which is used to adjust the lens to work with cover-glasses of various thicknesses. corrinoids See VITAMIN B12 . Corriparta subgroup See ORBIVIRUS. corrosive sublimate See MERCURY. cortex (1) Any of various external or outer layer(s) of a structure or organism – e.g. the outer differentiated tissue of certain LICHENS; in ciliates ‘cortex’ refers to the PELLICLE together with the INFRACILIATURE. (2) See ENDOSPORE. 196

coryza corticate Having a CORTEX. Corticiaceae See APHYLLOPHORALES. corticicolous Syn. CORTICOLOUS. corticolous (corticicolous) Growing on and/or in bark. (cf. EPIPHLOEODAL and ENDOPHLOEODAL.) corticosteroid synthesis See STEROID BIOCONVERSIONS. corticotype (ciliate protozool.) The morphological features of the CORTEX determined by staining (particularly silver staining) techniques. (See also SILVER LINE SYSTEM.) Corticoviridae (PM2 phage group) A family of icosahedral, lipid-containing, non-enveloped BACTERIOPHAGES which contain supercoiled ds cccDNA. Type species: BACTERIOPHAGE PM2. Possible member: bacteriophage 06N 58P (host: Vibrio). Corticovirus Currently the sole genus of the CORTICOVIRIDAE. cortina A remnant of the PARTIAL VEIL (q.v.) in a mature fruiting body. (‘Cortina’ is also used to refer to an intact partial veil.) Cortinariaceae See AGARICALES. Cortinarius See AGARICALES (Cortinariaceae) and MYCETISM. cortisol synthesis See STEROID BIOCONVERSIONS. Corynebacterium A genus of Gram-positive, aerobic, facultatively anaerobic, chemoorganotrophic, non-acid-fast, non-motile, asporogenous bacteria (order ACTINOMYCETALES, wall type IV). The genus contains saprotrophic species found e.g. in soil and vegetable matter (including e.g. some species previously classified in the genera Arthrobacter, Brevibacterium and Microbacterium), and a number of species which are parasitic or pathogenic in man and other animals; all the plant-pathogenic species have been reclassified in other genera (e.g. CURTOBACTERIUM, RHODOCOCCUS). Corynebacterium spp exhibit certain features common to all nocardioform actinomycetes – e.g. the presence of cell wall MYCOLIC ACIDS. The organisms are straight or curved, pleomorphic, often coryneform rods. Metabolism can be oxidative or fermentative. Catalase-positive. GC%: ca. 51–59. Type species: C. diphtheriae. C. autotrophicum. See XANTHOBACTER. C. betae. See CURTOBACTERIUM. C. bovis. Occurs e.g. associated with the cow’s udder. Unlike other Corynebacterium spp it contains tuberculostearic acid. C. diphtheriae. Cells rod-shaped, 0.3–0.8 × 0.8–8.0 µm. Toxinogenic strains of C. diphtheriae are the causal agents of DIPHTHERIA (see also DIPHTHERIA TOXIN and CROUP); the organisms may be isolated e.g. on tellurite–blood agar (see TELLURITE MEDIA) and subcultured to Loeffler’s serum. (Growth from Loeffler’s serum is used for the determination of cell morphology; cells grown on tellurite media have an atypical morphology.) The optimum growth temperature is 37° C. C. diphtheriae occurs in three main varieties, gravis, intermedius and mitis, which can be distinguished by cell and colonial morphology and by biochemical activity. All three varieties are urease-negative, and none can hydrolyse pyrazinamide; all produce acid (but no gas) from glucose, maltose and mannose, and some mitis strains can ferment sucrose [Book ref. 46, p. 1831]. Gravis strains typically form DAISY HEAD COLONIES (ca. 3 mm diam. at 24 hours/37° C) on blood–tellurite media; haemolysis is uncommon. Typically, starch is fermented in 24–48 hours. Very few cells contain METACHROMATIC GRANULES. Intermedius strains typically form small colonies (150 genera and >1000 species were described. However, many of these ‘field’ characteristics were found to be indeterminate in culture: e.g., colony forms may be lost, mucilage production and false branching may be variable, etc. Hence, a new scheme for generic assignments, based on properties of the organisms in pure culture, was proposed [JGM (1979) 111 1–61] and widely accepted. The genera were grouped into five sections: Section I. Unicellular; cells occur singly or in colonies. Reproduction occurs by equal binary fission (GLOEOBACTER, GLOEOCAPSA, GLOEOTHECE, SYNECHOCOCCUS, SYNECHOCYSTIS) or by budding (CHAMAESIPHON). This section includes organisms formerly of the Chroococcales, with Chamaesiphon from the Chamaesiphonales. Section II. Unicellular; cells always enclosed by a fibrous layer (F layer) external to the outer membrane. Reproduction occurs by multiple fission only (DERMOCARPA, XENOCOCCUS) or by multiple fission and binary fission (CHROOCOCCIDIOPSIS, DERMOCARPELLA, MYXOSARCINA, PLEUROCAPSA GROUP). Multiple fission occurs by rapid repeated binary fissions (unaccompanied by growth) within the F layer, resulting in the formation of BAEOCYTES which are released by rupture of the F layer. In species capable of binary fission, a series of divisions produces an aggregate of vegetative cells cemented together by their F layers; some or all of the cells in the aggregate eventually undergo multiple fission to form baeocytes. Motility, if it occurs, is restricted to baeocytes prior to the development of an F layer. [Developmental patterns: Book ref. 34, pp. 203–226.] This section includes the Chamaesiphonales (except Chamaesiphon) and the Pleurocapsales. Section III. Filamentous; growth occurs by intercalary cell division in one plane only (at 90° to the long axis of the trichome), giving rise to uniseriate, unbranched trichomes (cf. FALSE BRANCHING) composed only of vegetative cells (i.e., heterocysts and akinetes are not formed). The trichomes may be helical (SPIRULINA) or straight (LPP GROUP, OSCILLATORIA, PSEUDANABAENA). This section includes some genera of the former order Nostocales. Section IV. Filamentous; growth occurs by intercalary cell division in one plane only (at 90° to the long axis of the trichome), giving rise to uniseriate, unbranched trichomes (cf. FALSE BRANCHING); heterocysts are formed in the absence of combined nitrogen, and akinetes are produced by some members. Reproduction occurs by random breakage of trichomes, or by germination of akinetes if formed; hormogonia are produced by CALOTHRIX, NOSTOC and SCYTONEMA, but not by ANABAENA, CYLINDROSPERMUM or NODULARIA. Section IV includes those genera of the Nostocales not included in section III. Section V. Filamentous; growth occurs by intercalary cell division which may occur in more than one plane, i.e., some cells in the mature trichome may divide in a plane parallel to the long axis of the trichome. Thus, the mature trichome may be partly multiseriate with uniseriate lateral (true) branches (FISCHERELLA), but may readily break up into cell aggregates (CHLOROGLOEOPSIS). Heterocysts are formed in the absence of combined nitrogen; akinetes are formed by some members. Reproduction occurs by random breakage of trichomes, by the formation of hormogonia, and (in some species) by the formation and germination of akinetes. Section V is taxonomically equivalent to the former order Stigonematales.

Many genera have yet to be incorporated in this scheme: see e.g. APHANIZOMENON, COELOSPHAERIUM, DACTYLOCOCCOPSIS, MICROCYSTIS, STARRIA, TRICHODESMIUM. [Isolation, media etc: Book ref. 45, pp. 212–246.] Cyanobacteriales An order proposed for the CYANOBACTERIA [IJSB (1978) 28 1–6] but not accepted as legitimate owing to the lack of a genus named Cyanobacterium; however, the proposal of a new genus Cyanobacterium [Ann. Mic. (1983) 134 B 21–36] paves the way for legitimization of the order. Cyanobacterium See SYNECHOCOCCUS and CYANOBACTERIALES. cyanobiont A cyanobacterial symbiont: see e.g. ANABAENA and NOSTOC. (cf. PHYCOBIONT.) Cyanobium See SYNECHOCOCCUS. cyanocobalamin See VITAMIN B12 . Cyanocyta See GLAUCOPHYTA. cyanogen bromide (CNBr) A reagent used e.g. for the IMMOBILIZATION of a protein on the surface of a support; CNBr binds to the support (forming a ‘CNBr-activated’ support) and then binds spontaneously to primary amino groups on the protein. The instability of the isourea bond (between the activated support and protein) may lead to some loss of the immobilized protein; this may be avoided e.g. by cross-linking the protein with glutaraldehyde. cyanogenic Having the capacity to produce cyanide (see also CYANIDE sense 2). cyanoguanidine Dicyandiamide, a NITRIFICATION INHIBITOR. cyanomycin An antibiotic produced by ‘Streptomyces cyanoflavus’ and reported to be identical to PYOCYANIN [J. Antibiot. (1969) 22 49–54 cited in JB (1980) 141 156–163]. cyanophage Any VIRUS whose host is a cyanobacterium (‘bluegreen alga’). (cf. PHYCOVIRUS.) Cyanophages may be virulent or temperate, and have been isolated from filamentous and unicellular species – including members of the LPP group (cyanophages LPP-1, LPP-2), Nostoc (N1, N2), and Anabaena (A1, A2); lysis of infected intercalary cells in filamentous species results in progressive fragmentation of the filament. [Ann. Mic. (1983) 134 B 43–59; classification and nomenclature: Intervirol. (1983) 19 61–66.] cyanophilic Having an affinity for blue dyes such as LACTOPHENOL COTTON BLUE. Cyanophora See GLAUCOPHYTA. cyanophycean starch A glycogen-like storage polysaccharide found in cyanobacteria; the polysaccharide occurs as granules or rods located between the thylakoids. cyanophycin (multi-L-arginyl-poly(L-aspartic acid); arg-poly(asp)) A high-MWt polymer consisting of equal amounts of L-aspartic acid and L-arginine; the L-aspartic acid residues occur in a linear chain, and each residue is linked via its free carboxyl group to the a-amino group of an arginine residue. Granules of cyanophycin (a granules, ‘structured granules’) occur in most cyanobacteria. The polymer is synthesized independently of ribosomes and serves primarily as a nitrogen reserve in both vegetative cells and heterocysts. Under CO2 -limiting conditions, cyanophycin may also serve as a source of carbon and energy by an ARGININE DIHYDROLASE pathway, at least in some species. [Review: ARM (1984) 38 13–16.] cyanophytes CYANOBACTERIA. cyanosis (med., vet.) A bluish discoloration or darkening of the skin and mucous membranes due to inadequate oxygenation of the blood. cyanosomes Cyanobacterial PHYCOBILISOMES. Cyanothece See SYNECHOCOCCUS. cyanotoxin Any toxin produced by a member of the CYANOBACTERIA (q.v. for examples). 210

cyclolysin more essential stages of its life cycle in the vector. (See e.g. PLASMODIUM and TRYPANOSOMA.) Cyclidium A genus of ciliates (order SCUTICOCILIATIDA) which occur e.g. in soil, fresh water (including hot springs) and marine habitats. Cells: typically ovoid and generally small, ca. 15–40 µm; the cell surface is typically not densely ciliated, but those cilia which are present tend to be long, and there is often one or more longer caudal cilia. cyclin A type of protein involved in the regulation of the eukaryotic CELL CYCLE. During the cycle, molecules of cyclin accumulate intracellularly at specific stages and form complexes with certain PROTEIN KINASES. Phosphorylation of the kinase part of the complex – and subsequent (partial) dephosphorylation at an appropriate point in the cycle – leads to activation of the kinase. The activated kinase phosphorylates certain proteins which then promote onward cycling; it can also bring about UBIQUITIN-dependent degradation of the cyclin – so that the intracellular concentration of cyclin falls sharply on passage through the checkpoint. There are various types of cyclin, and different types may form complexes with protein kinases at different cell-cycle checkpoints; for example, different types of cyclin form complexes with the yeast protein kinase Cdc2 in order to mediate passage through (a) the start checkpoint, and (b) the G2 → M checkpoint. cyclitol antibiotics ANTIBIOTICS which contain a cyclic alcohol – e.g. AMINOGLYCOSIDE ANTIBIOTICS (which contain a substituted INOSITOL). cycloalkanes See HYDROCARBONS. cycloamyloses Syn. SCHARDINGER DEXTRINS. cyclochlorotine Syn. CHLOROPEPTIDE. cyclodextrins Syn. SCHARDINGER DEXTRINS. cycloguanil See CHLORGUANIDE. cyclohexane metabolism See HYDROCARBONS. cycloheximide (Actidione; b-[2-(3,5-dimethyl-2-oxocyclohexyl)2-hydroxyethyl]-glutarimide) An ANTIBIOTIC produced by certain strains of e.g. Streptomyces griseus; it is a by-product of streptomycin manufacture. Cycloheximide is active against many fungi and other eukaryotes (bacteria are not affected), acting primarily by inhibiting PROTEIN SYNTHESIS; e.g., it prevents translocation by binding to the 60S subunit of 80S ribosomes. Ribosomes from different organisms may differ in sensitivity. Only the yeast-like forms of certain dimorphic fungi (e.g. Blastomyces dermatitidis, Histoplasma capsulatum) are susceptible to cycloheximide. Certain stereoisomers of cycloheximide (e.g. naramycin B) have been isolated from Streptomyces cultures; these are generally less active than cycloheximide against fungi. Streptovitacins are monohydroxyl-substituted cycloheximides produced by S. griseus; streptovitacin A appears to resemble cycloheximide in its mode of action. cyclolysin An RTX TOXIN produced by species of Bordetella. The ∼177 kDa protein is encoded by gene cyaA; activity of the toxin depends on post-translational modification in which a long-chain fatty acid is linked covalently at a specific lysine residue. The toxin is secreted by an ABC EXPORTER. Cyclolysin has ADENYLATE CYCLASE, haemolysin and poreforming activity. A range of eukaryotic cells are susceptible; within the target cell cyclolysin is activated by CALMODULIN. The principal role of cyclolysin in WHOOPING COUGH may involve inhibition of the activity of phagocytic cells (e.g. macrophages) by raising their intracellular levels of cAMP. Moreover, by suppressing anti-bacterial activity in phagocytes,

Cyathomonas See CRYPTOPHYTES. Cyathus A genus of fungi (order NIDULARIALES) in which the basidiocarp is funnel-shaped (ca. 1 cm across), the opening of the funnel being closed by a membrane (epiphragm) in the immature fruiting body. Each of the flattened, discoid peridioles is attached to the lower, inner surface of the peridium (i.e., funnel) by means of a complex structure which consists essentially of three components joined end to end. Attached directly to the peridium is the sheath (a short cord of aggregated hyphae) to which is joined the middle piece (a narrow extension of the sheath); the middle piece is attached to an elongated sac (the purse) to the outside of which is attached the peridiole. The purse contains a long thread of coiled hyphae (the funiculus or funicular cord ), one end of which is firmly attached to the peridiole while the other (unattached) end carries a strongly adhesive body (the hapteron). When drops of rain fall into the funnel-shaped peridium (or ‘splash cup’) the peridioles are ejected by the strong upthrust of water on their undersurfaces; each peridiole flies through the air, trailing its funiculus, until the hapteron adheres to e.g. a blade of grass. cycad symbioses See NOSTOC. cyclaridine An ANTIVIRAL AGENT – the carbocyclic analogue of vidarabine; its activity resembles that of VIDARABINE in cell cultures, but it is resistant to deamination by adenosine deaminase. cycles of matter See CARBON CYCLE, NITROGEN CYCLE and SULPHUR CYCLE. cyclic AMP (cAMP) Adenosine 3′ ,5′ -cyclic monophosphate: a cyclic nucleotide synthesized from ATP by ADENYLATE CYCLASE; cAMP is degraded to AMP by cAMP phosphodiesterase (EC 3.1.4.17).

adenine O HO P O

5′

CH2 O

H

H 3′

O

1′

H 2′

H

OH

CYCLIC AMP (cAMP)

cAMP is an important regulatory molecule in various types of cell. In prokaryotes, cAMP is involved in CATABOLITE REPRESSION and e.g. in stimulating fruiting in the MYXOBACTERALES. [cAMP in prokaryotes: MR (1992) 56 100–122.] In eukaryotes, cAMP is involved in various regulatory and developmental processes (see e.g. DICTYOSTELIUM); it apparently functions mainly by regulating the activity of PROTEIN KINASES. cAMP-dependent protein kinase A (PKA) consist of two types of subunit: the catalytic (C) and regulatory (R) subunits; the inactive form of PKA consists of a dimer of R subunits to which are bound two C subunits. cAMP activates PKA by binding to the R subunits; this causes the release of both C subunits – which (separately) are then able to carry out their catalytic roles. The active C subunits have a wide range of functions in both cytoplasm and nucleus – including e.g. regulation of certain transcriptional events in the nucleus. cyclic octadepsipeptide antibiotics QUINOXALINE ANTIBIOTICS. cyclical transmission A mode of transmission of a parasite by a VECTOR (sense 1) in which the parasite undergoes one or 211

cyclo-oxygenase cyprofuram See PHENYLAMIDE ANTIFUNGAL AGENTS. Cyrtophorida See HYPOSTOMATIA. cyrtos (cytopharyngeal basket; nasse; pharyngeal basket) A (frequently curved) type of CYTOPHARYNGEAL APPARATUS whose walls are strengthened by longitudinal nematodesmata (which arise at apical kinetosomes) and are lined with extensions of POSTCILIARY MICROTUBULES; toxicysts are absent. The cyrtos is characteristic of the HYPOSTOMATIA. (cf. RHABDOS.) cyst A specialized microbial cell produced either in response to adverse environmental conditions or as a normal part of the life cycle. During cyst formation (encystment), an organism produces a thick or thin wall within which it becomes totally enclosed. Cysts are usually resistant to desiccation, and may be resistant to e.g. ultraviolet radiation and/or heat. (a) (bacteriol.) Cyst formation is uncommon among bacteria; most studies on bacterial cyst formation have been carried out on species of AZOTOBACTER, particularly A. vinelandii. In Azotobacter spp, encystment can be promoted in vitro by the provision of substrates such as b-hydroxybutyrate, and it has been generally supposed that the intracellular accumulation of PHB is a necessary pre-requisite for cyst formation; however, it has been proposed that the stimulus for encystment may be related to the extracellular levels of both carbon and nitrogen sources [SBB (1986) 18 23–28]. During encystment, cells lose their flagella and become spheroidal; these heavily encapsulated cells (‘precysts’) typically accumulate PHB. Membranous blebs develop at the cell surface, and these subsequently detach and coalesce – forming the fragmented outer layer (exine) of the cyst wall. Later, the cyst wall develops an electron-transparent inner layer (intine). The cyst wall contains ALGINATE together with protein and lipid; the exine is particularly rich in polyguluronic acid (and Ca2+ ), while the intine is richer in polymannuronic acid. Azotobacter cysts are metabolically dormant, and they can remain viable in dry soil for many years; they are more resistant than the vegetative cells to desiccation, sonication and ultraviolet radiation, but they are not significantly more resistant to heat. Azotobacter-like ‘lipid cysts’ are formed by some members of the Methylococcaceae. (See also MICROCYST.) (b) (protozool.) Cysts are formed e.g. by some amoebae, ciliates and phytoflagellates. During encystment, structures such as cilia or flagella are lost or resorbed, and considerable reorganization of internal structures may occur; the cell becomes enclosed by a thin or thick, commonly multilayered wall, the outer-most layer(s) being termed the ectocyst or exocyst, the innermost layer(s) the endocyst, and intermediate layer(s) the mesocyst. Cyst walls vary in composition, according to species; they commonly contain a high proportion of protein, while e.g. cellulose occurs in the endocyst of Acanthamoeba spp, chitin apparently occurs in Entamoeba cysts [BBRC (1982) 108 815–821], and sulphated glycosaminoglycans occur in the mesocyst in Histriculus similis [JGM (1983) 129 829–832]. Cysts of CHRYSOPHYTES have silica walls. (In certain loricate or testate organisms – e.g. Euglypha spp – a cyst is formed when the organism withdraws into its lorica/test and plugs the aperture.) Excystment (the release of one or more vegetative cells from the cyst) may involve rupture of the cyst wall (possibly as a result of the intake of water) and/or enzymic dissolution of the wall; in e.g. Naegleria gruberi the cell leaves the cyst via a pore which becomes unplugged, while in Acanthamoeba a lid-like operculum is removed from an exit aperture in the cyst wall. In many protozoa the cyst serves a protective function, allowing the organism to survive e.g. the absence of food,

the pathogen may be able to establish an intracellular carrier state. The raised levels of cAMP in epithelial cells may account for the secretion of fluid/mucus. cyclo-oxygenase See PROSTAGLANDINS. cycloparaffins See HYDROCARBONS. cyclophosphamide See IMMUNOSUPPRESSION. cyclopiazonic acid A MYCOTOXIN produced by species of Aspergillus and Penicillium (e.g. A. flavus, A. oryzae, P. verrucosum (‘P. cyclopium’) and P. griseofulvum (‘P. patulum’)). It is toxic e.g. for chickens [AEM (1983) 46 698–703], rats and calves. D-cycloserine (D-4-amino-3-isoxazolidone) A broad-spectrum ANTIBIOTIC obtained from strains of Streptomyces spp or synthesized chemically. It acts as an analogue of D-alanine, competitively inhibiting the two enzymes (alanine racemase and D-alanyl-Dalanine synthetase) involved in the biosynthesis of PEPTIDOGLYCAN. D-Cycloserine is actively taken up by the D-alanine/glycine transport system of the cell, and a mutation which alters this transport system can result in resistance to the antibiotic. (Methanococcus vannielii lacks peptidoglycan but is nevertheless susceptible to D-cycloserine [Book ref. 157, p. 529].) cyclosis Syn. CYTOPLASMIC STREAMING. Cyclospora A genus of protozoa (suborder EIMERIORINA) which form disporic, dizoic oocysts. [C. cayetanensis as a diarrhoeal agent: RMM (1996) 7 143–150.] cyclosporin A A hydrophobic peptide obtained from certain hyphomycetes (Cylindrocarpon lucidum, Tolypocladium inflatum); it is a powerful immunosuppressive drug (see IMMUNOSUPPRESSION) which appears to act mainly on T cells. Cyclotella See DIATOMS. Cydia pomonella GV See GRANULOSIS VIRUSES. Cylindrocarpon A genus of fungi (class HYPHOMYCETES) which include organisms previously classified as species of Fusidium. Some species have teleomorphs in the genus Nectria. (See also CYCLOSPORIN A and FUSIDIC ACID.) Cylindrocystis A genus of saccoderm DESMIDS. Cylindrogloea bacterifera See CHLOROCHROMATIUM AGGREGATUM. Cylindrospermum A genus of filamentous CYANOBACTERIA (section IV) in which the heterocysts occur only at the ends of the trichomes; akinetes are always adjacent to heterocysts. Hormogonia are formed by fragmentation of whole trichomes. GC%: 42–47. Cylindrosporium See MELANCONIALES. Cylindrotheca See DIATOMS. Cymbella See DIATOMS. Cymbidium mosiac virus See POTEXVIRUSES. Cymbidium ringspot virus See TOMBUSVIRUSES. Cymbomonas See MICROMONADOPHYCEAE. Cyniclomyces A genus of fungi (family SACCHAROMYCETACEAE) which form budding yeast cells and pseudomycelium; elevated levels of CO2 are needed for growth. One species, C. guttulatus, isolated from the faeces and stomach of rabbits. [Book ref. 100, pp. 125–129.] Cyphelium See CALICIALES. cyphella (lichenol.) A round depression or pore – visible as a small white pit ca. 0.5–2.0 mm diam. – in the lower surface of the thallus in Sticta spp. The lower cortex forms a protruding rim around the edge of the cyphella, a medullary layer of rounded fungal cells lining the depression. Cyphellae are believed to facilitate gas exchange. [New Phyt. (1981) 88 421–426]. (cf. PSEUDOCYPHELLA.) Cypovirus Syn. CYTOPLASMIC POLYHEDROSIS VIRUS GROUP. 212

cytochrome oxidase desiccation, and/or unfavourable temperatures. Such ‘resistant cysts’ are generally dormant and may remain viable for years under appropriate conditions. Many such cysts (e.g. those of some euglenoid flagellates) are highly resistant to desiccation; however, those of e.g. Didinium and Euplotes cannot withstand drying, but can remain viable in water for long periods. Resistant cysts may allow dissemination of the organism e.g. by wind or by birds or animals. In parasitic protozoa – e.g. ENTAMOEBA, coccidia, GIARDIA – cysts are the form in which the parasite is transmitted from one host to another. In some protozoa reproductive cysts are formed as a normal part of the life cycle; these may not be more resistant than the vegetative cell to adverse environmental conditions. For example, Colpoda spp form thin-walled cysts within which asexual fission occurs, and can also form thick-walled resistant cysts under adverse conditions. (See also e.g. ICHTHYOPHTHIRIUS.) Some protozoal cysts may serve both reproductive and protective (and disseminative) functions (e.g. the oocysts of the EIMERIORINA). (See also ACTINOPHRYS and ACTINOSPHAERIA.) cystathione See e.g. Appendix IV(d). cysteamine 2-Mercaptoethylamine (= b-aminoethanthiol): see e.g. PANTOTHENIC ACID. L-cysteine biosynthesis See Appendix IV(c). cysteine protease (1) See APOPTOSIS. (2) Syn. thiol PROTEASE. cystibiotics Class IIa BACTERIOCINS (q.v.). cystic fibrosis (CF) An inheritable disease [Review: Lancet (1998) 351 277–282] usually involving defective transmembrane transport of chloride by an ABC TRANSPORTER. Typically, the lungs are congested with a viscid dehydrated mucus (containing e.g. raised levels of calcium and magnesium ions) which may become infected with organisms such as Burkholderia (formerly Pseudomonas) cepacia [review: RMM (1995) 6 1–16], mycobacteria and Pseudomonas aeruginosa; such infections often persist. Patients with CF are frequently given prolonged antibiotic therapy, but this may not prevent colonization of the lungs with e.g. mucoid (ALGINATE-forming) strains of Pseudomonas aeruginosa [mucoidy of P. aeruginosa in CF: JB (1996) 178 4997–5004]; this is associated with a poor prognosis because the alginate may protect the bacteria from phagocytosis, pulmonary surfactant and antibiotics. It has been reported that high levels of salt (NaCl) on CF airway epithelia may permit bacterial colonization by inhibiting anti-bacterial activity normally associated with this habitat [Cell (1996) 85 229–236]. (See also QUORUM SENSING.) Results of studies on the molecular epidemiology of P. aeruginosa in a CF outpatient clinic indicate that crossinfection is not common within the clinic, and that acquisition of infection from a common source is unlikely [JMM (2001) 50 261–267]. It was suggested that long-term colonization of the lungs of CF patients with Stenotrophomonas maltophila (formerly Xanthomonas maltophila) may be a significant factor in prognosis [RMM (1997) 8 15–19]. This environmentally common, Gramnegative, non-glucose-fermenting bacillus [description: IJSB (1993) 43 606–609] is now frequently isolated from the respiratory specimens of CF patients (and is also associated with disease in immunocompromised individuals, cancer patients and recipients of transplants). [Identification/detection of S. maltophila by a PCR-based approach: JCM (2000) 38 4305–4309.] [Genetic basis, treatment etc. of CF: Book ref. 214.] cystidium (mycol.) A large, elongated, sterile cell which occurs among the basidia in the hymenia of certain basidiomycetes. Cystidia vary greatly in size and form, but they usually project

some way beyond the tips of the basidia. Their function is largely unknown; however, those which arise from the surfaces of the lamellae of certain species of Coprinus appear to function as ‘spacers’ – maintaining a small but significant distance between adjacent lamellae, thus facilitating spore dispersal. cystine–lactose–electrolyte-deficient medium See CLED MEDIUM. cystine–tellurite–blood agar See TELLURITE MEDIA. cystitis Inflammation of the urinary bladder. Symptoms: frequent, painful micturition, sometimes with haematuria, fever etc. Cystitis may result from the spread of an infection upwards from the urethra or downwards from the kidney. The former is more common, with Escherichia coli (see UPEC) and Proteus spp being the most common causal agents; other causal agents include enterococci and Staphylococcus saprophyticus. Treatment may involve e.g. copious fluid intake and therapy with broad-spectrum antibiotics. Certain adenoviruses (e.g. type 11) have been associated with haemorrhagic cystitis (mainly in children). (See also URINARY TRACT INFECTION.) Cystobacter See MYXOBACTERALES. Cystodinium A genus of DINOFLAGELLATES in which the vegetative cells are unicellular and non-motile, and reproduce by the formation of zoospores. Cystomyces See UREDINIOMYCETES. Cystoseira See PHAEOPHYTA. cystosorus A cluster of cysts: see e.g. PLASMODIOPHOROMYCETES. Cystotheca See ERYSIPHALES. Cystoviridae (f6 phage group) A family of BACTERIOPHAGES containing one genus (Cystovirus) and one member: BACTERIOPHAGE f6. Cystovirus See CYSTOVIRIDAE. cystozoite (bradyzoite) In certain coccidia: a stage within host tissues (see e.g. TOXOPLASMOSIS). cytarabine (1-b-D-arabinofuranosylcytosine; ara-C; cytosine arabinoside) An ARABINOSYL NUCLEOSIDE originally investigated as a possible systemic ANTIVIRAL AGENT for disseminated herpesvirus infections; toxicity has limited its clinical use. cytidine See NUCLEOSIDE and Appendix V(b). cytidine deaminase See RNA EDITING. cytoadherence See MALARIA. cytoadhesin subfamily A category within the INTEGRIN family which includes CD41b/CD61. cytobiosis SYMBIOSIS in which one symbiont occurs within the cells of the other. cytochalasins A family of fungal secondary metabolites (POLYKETIDE derivatives) – cytochalasins A, B, C etc. – which are formed e.g. by species of Aspergillus, Helminthosporium and Phomopsis. Cytochalasins bind to one end of an ACTIN microfilament (the fast-growing or ‘barbed’ end) and inhibit the addition of further monomers – thus inhibiting e.g. phagocytosis, amoeboid movement, the intracellular development of certain viruses, and other microfilament-dependent functions. (Cytochalasin B apparently slows, but does not prevent, the addition of actin monomers [JCB (1986) 102 282–288].) Cytochalasins A and E enhance branching in certain fungi (see GROWTH (fungal)). cytochrome See CYTOCHROMES. cytochrome oxidase In an ELECTRON TRANSPORT CHAIN a (terminal) cytochrome which transfers electrons to molecular oxygen, reducing it to water. Cytochrome oxidases include cyts aa3 , a1 , d and o (see CYTOCHROMES). Bacteria typically have more than one type of cytochrome oxidase. The electron transport chain in the animal MITOCHONDRION appears to have only one type 213

cytochrome oxidase test of cytochrome oxidase, cyt aa3 , which resembles the bacterial cyt aa3 in containing two haem a molecules and two copper atoms; in at least some plant mitochondria there is an additional CYANIDE-resistant cytochrome oxidase. (See also RESPIRATORY INHIBITORS.) cytochrome oxidase test See OXIDASE TEST. cytochromes A class of haemoproteins in which the HAEM (sense 1) is usually linked to the protein via the 5th and 6th coordinate positions of the haem iron; cytochromes participate in many types of electron transfer reaction (see e.g. ELECTRON TRANSPORT CHAIN and PHOTOSYNTHESIS), such reactions involving the alternate oxidation and reduction of the haem iron. The Em.7 (see REDOX POTENTIAL) of most cytochromes falls within the approximate range −100 to +500 mV. Cytochrome nomenclature. Cytochromes are classified primarily by the nature of their haem group(s); individual cytochromes within a given class may be distinguished by subscripts (e.g. c1 , c2 , c3 etc) or – see later – they may be designated by certain of their absorption characteristics. Cytochromes a (cyts a) contain haem a (which has a formyl group at the C-8 position, and a long hydrophobic chain at the C-2 position of the PORPHYRIN). Cytochromes b contain haem b (= protohaem: see HAEM). Cytochromes c contain haem c (a mesohaem), the haem being linked to the protein via thioether bonds (between the ethyl substituents of the haem and cysteine residues in the protein) as well as via the coordinate bonds. Some c-type cytochromes (e.g. cyts c2 , c555 ) have a single haem attached near the Nterminal of the protein, while others have a single haem attached near the C-terminal; the latter, which include the c′ cytochromes (= cytochromoids), differ chemically and spectroscopically from other c-type cytochromes. Cytochromes d contain a CHLORIN. Certain cytochromes have more than one haem group, while others may contain e.g. a flavin group. Some cytochromes are often referred to by their original names, even though such names do not reflect current classification; thus e.g. cyt a2 is now cyt d, and cyt o is a b-type cytochrome. Identification of cytochromes. Cytochromes may be identified/quantified by various methods, often e.g. by spectrophotometry – in which a given type of cytochrome may be detected, in situ, by its characteristic absorption pattern in the visible regions of the spectrum. Commonly a difference spectrum is determined: e.g., the absorption spectrum of a given cytochrome in the reduced state minus its absorption spectrum in the oxidized state (cf. CO DIFFERENCE SPECTRUM); such a spectrum often exhibits a maximum absorption peak in each of three bands: the a-band (ca. 540–650 nm), the b-band (ca. 510–530 nm) and the g-band (= Soret band ) (ca. 400–450 nm). In some cases a cytochrome may be designated by its absorption peak (in the reduced state) within the a-band – e.g., cyt b-557 (= cyt b557 ). Spectroscopy can sometimes lead to an incorrect in situ identification of a cytochrome [see e.g. JGM (1984) 130 3055–3058]. In some cases it may be necessary to extract the haem, bind to it (coordinately) two pyridine molecules per molecule, and examine by spectroscopy the resulting dipyridine ferrohaemochrome (= pyridine haemochrome) – reduced e.g. with sodium dithionite – in an alkaline pyridine solution. For each class of cytochromes, the corresponding dipyridine ferrohaemochrome a-absorption peak falls within a narrow waveband: cyts a 580–590 nm; cyts b 556–558 nm; cyts c 549–551 nm; cyts d 600–620 nm. [Analysis of cytochromes: Book ref. 138, pp. 285–328.] Cytochrome–ligand binding. See e.g. AZIDE, CARBON MONOXIDE and CYANIDE.

Cytochromes in eukaryotes. Cytochromes occur e.g. in the mitochondrial ELECTRON TRANSPORT CHAIN (q.v.) and in photosynthetic systems (see PHOTOSYNTHESIS). Many cells also contain e.g. certain b-type cytochromes – such as cyt b5 and a cyt P-450 – associated with the endoplasmic reticulum. The mammalian cyt P-450 – the cytochrome–carbon monoxide complex absorbs at 450 nm – occurs in liver cells and mediates in hydroxylation reactions involving sterols and other lipidsoluble substances; an analogous cyt P-450 occurs e.g. in many fungi (see e.g. AZOLE ANTIFUNGAL AGENTS and HYDROCARBONS). Cytochromes appear to be absent in e.g. certain parasitic protozoa – including bloodstream forms of trypanosomes and intracellular stages of Leishmania donovani. Cytochromes in prokaryotes. Cytochromes occur in both aerobic and anaerobic respiratory chains in the CYTOPLASMIC MEMBRANE; they also occur in the cytoplasm and/or periplasmic region in some cells, and appear to occur in certain photosynthetic REACTION CENTRES. In bacteria, cytochromes vary – qualitatively and quantitatively – from one species to another, and even in a given species under different growth conditions. [Cytochromes in Escherichia coli under different growth conditions: JGM (1982) 128 1685–1696.] Various cytochromes may act as CYTOCHROME OXIDASES, and it is usual for a given bacterium to have more than one type of cytochrome oxidase. Generalized patterns of cytochromes occur in the various categories of bacteria. Gram-positive aerobic chemoheterotrophs typically have a pattern of the bcaa3 o type, i.e., including two types of cytochrome oxidase; exceptions include e.g. Brochothrix thermosphacta which has only one cytochrome oxidase (aa3 ). Gram-negative chemoheterotrophs (including e.g. enterobacteria and pseudomonads) are, by comparison, more heterogeneous in their cytochrome patterns under aerobic conditions; typically, cyt aa3 is not formed (though it is in e.g. some pseudomonads, many methylotrophs, and Rhizobium spp), the cytochrome pattern frequently being of the bcoa1 d type, but often without cyt c. Cyts a and d are not formed e.g. by Pseudomonas fluorescens, or by certain other pseudomonads, so that these organisms may have patterns of the bco or bo type. Cytochrome oxidases are often absent or greatly decreased during anaerobic respiration. In at least some pseudomonads (and e.g. Thiobacillus denitrificans) which carry out DENITRIFICATION, cyt d1 c (= cd1 ) acts as a nitrite reductase. Chemolithotrophs often have cytochrome patterns of the bcaa3 o type. All members of the RHODOSPIRILLALES appear to contain c-type cytochromes, and most or all appear to have b-type cytochromes. Specialized cytochromes or cytochrome patterns occur in some bacteria; thus, e.g. Pseudomonas putida contains a soluble cyt P-450 which, together with an iron–sulphur protein and an FAD-containing reductase, effects hydroxylation of e.g. camphor in a cyclic reaction sequence. [Structure and chemistry of cyt P450 from P. putida: Book ref. 146, pp. 157–206.] (See also METHYLOTROPHY and RHP.) Cytochromes appear to be absent from some facultative and obligate anaerobes. [Structure, function and evolution of cytochromes (review): Prog. Biophys. Mol. Biol. (1985) 45 1–56.] (See also BENZIDINE TEST and OXIDASE TEST.) cytochromoids See CYTOCHROMES. cytocidal (adj.) Able to kill cells. cytoductant See CYTODUCTION. cytoduction A cross in which two cells undergo cytoplasmic fusion but do not undergo nuclear fusion (karyogamy) owing to a chromosomal mutation; each haploid progeny cell (cytoductant, 214

cytokines a given type of STAT relays the signal for only some type(s) of cytokine – thus permitting different cytokines to initiate different signals in the same cell. Phosphorylated STATs form homo- or heterodimers that enter the nucleus and promote transcription of particular gene(s). [STATs: TIBS (2000) 25 496–502.] As mentioned, a given cytokine may cause diverse effects. For example, the binding of tumour necrosis factor (TNF) to its receptor can result in activation of caspases (and APOPTOSIS) – or e.g. transcription of specific genes through activation of a major transcription factor: nuclear factor-kB (NF-kB). In the latter pathway, the binding of TNF to its receptor promotes phosphorylation (and consequent degradation) of a certain protein (IkBa) which, by binding to NF-kB, inactivates it; that is, phosphorylation (degradation) of IkBa results in the activation of NF-kB. NF-kB is important e.g. in the development of an inflammatory response; it promotes transcription of a range of genes – including those encoding TNF-a, IL-1b and IL-8. In general, the binding of cytokines to their receptors may initiate cellular responses that range from secretion (of cytokines etc.), differentiation or proliferation to chemotaxis or apoptosis; currently, many of the signalling pathways in eukaryotic cells are incompletely understood. [Signalling mechanisms in prokaryotes and eukaryotes: Book ref. 218, pp 89–162; Book ref. 226, pp 111–140.] Note regarding nomenclature of cytokines. The name of a cytokine does not necessarily correlate with its primary function(s) in vivo. For example, tumour necrosis factor was initially identified as an anti-tumour agent but is now known to be a central mediator in host defence and inflammation. Again, some interleukins, initially thought to mediate only leukocyte–leukocyte interactions, are now known to involve other types of cell; thus, e.g. interleukin-8 is secreted by endothelial cells and is classified as a chemokine. Cytokines as factors in health and (infectious) diseases. Various roles have been attributed to cytokines in normal physiology and development. However, the contribution of individual cytokines in vivo has been difficult to establish experimentally – not least because of the complexity of the system and the existence of biochemical redundancy among cytokines; hence, in some cases, the function(s) of a cytokine have been inferred from the effects attributed to inherited deficiencies in the synthesis or activity of that cytokine (and/or its receptor). In other cases, the role(s) of cytokines have been inferred from studies on knockout mice in which genes of particular cytokine(s) have been rendered non-functional. In diseases of microbial aetiology, cytokines typically have protective roles – e.g. in processes such as ANTIBODY FORMATION and INFLAMMATION. However, dysregulation of cytokines (enhanced production, imbalance, inhibition) may be a major factor in pathogenesis. In some cases, the severity of, or susceptibility to, disease has been found to vary in different individuals according to the nature of the TNF-a gene promoter – particular polymorphisms in the promoter region of the gene being associated with enhanced production of the cytokine; this has been reported in cerebral MALARIA [Nature (1994) 371 508–510] and in ENDOTOXIC SHOCK [JAMA (1999) 282 561–568]. Again, polymorphisms in the gene encoding IL-1b have been associated with an increased risk of gastric cancer from Helicobacter pylori infection [Nature (2000) 404 398–402]. In pyelonephritis caused by Escherichia coli, the cytokines IL6 and IL-8 appear to be prominent – levels of IL-6 correlating

heteroplasmon) contains the nucleus of one parent cell but may contain cytoplasmic elements from both parent cells. cytofluorometry FLOW CYTOMETRY which involves the detection of specific fluorescence or FLUOROCHROME markers. cytogamy (selfing) (ciliate protozool.) The occurrence of AUTOGAMY (instead of conjugation) in each of two ciliates which have paired. cytohet (cytoplasmic heterozygote) A eukaryotic cell which is HETEROZYGOUS for one or more CYTOPLASMIC GENES. cytokines In the human and animal body: a heterogeneous population of (glyco)proteins which form a dynamic network of intercellular messenger molecules that regulate various aspects of physiology, including the immune response to infection. (This describes, but does not define, cytokines; workers in the field have not yet indicated the essential difference(s) between those molecules which are currently regarded as cytokines and certain other regulatory molecules – thus precluding a formal definition at the present time.) Cytokines may be distinguished from the (protein) hormones in that (i) a given cytokine may be synthesized by different types of cell and/or may act on different types of cell; (ii) cytokines typically act on target cells near the source of cytokine – although if secreted into the circulatory system they may act on distant cells; (iii) cytokines may cause diverse effects (e.g. when acting on different cells under different conditions); (iv) different types of cytokine may give rise to the same physiological effect; and (v) some cytokines can act as mitogens. Two sources [Book refs 218 and 226] recognize the following as cytokines: COLONY-STIMULATING FACTORS, INTERFERONS, INTERLEUKINS, cytotoxic agents such as tumour necrosis factor (see TNF), growth factors and CHEMOKINES. Cytokines are synthesized mainly by leukocytes (white blood cells); some cytokines are synthesized by stationary cells (e.g. endothelial cells). Although most cytokines are soluble (secreted) products, some are, or can be, membrane-associated. In general, transcription of cytokine-encoding genes is inducible by appropriate exogenous or endogenous stimuli. An example of an exogenous stimulus is the binding of lipopolysaccharide to CD14 receptors on macrophages (see CD14); endogenous stimuli can arise e.g. during viral infection. On release, cytokines bind to specific receptors on target cells. Cytokine receptors are divided into a number of families which differ e.g. in structure. (Some of the receptors found on macrophages and T lymphocytes can act as receptors for human immunodeficiency virus (HIV). Cytokine receptors have also been reported to act as binding sites for certain other viruses, including human (alpha) herpesvirus 1.) Interestingly, receptor molecules can be shed from cells; such isolated receptors can e.g. bind to (and antagonize) the corresponding cytokine, or they can bind to other cells – which may then be stimulated by the given cytokine. The binding of a cytokine to its cognate receptor initiates an intracellular signal, the nature of which depends e.g. on the type of cell and cytokine and on the environmental and intracellular conditions under which binding takes place. Cytokine–receptor binding characteristically results (either directly or indirectly) in the activation of kinase(s) at certain stage(s) within the signalling pathway. In one intracellular signalling pathway (triggered by many of the interleukins), the binding of cytokine leads to activation of a tyrosine kinase of the JAK (Janus kinase) family which, when activated, transmits the signal by phosphorylating a molecule of the so-called ‘signal transducers and activators of transcription’ (STATs); STATs exist in different forms, and 215

cytokinesis to be down-regulated in naive CD4+ cells [PNAS (1999) 96 3023–3028].) Studies carried out in vitro and in vivo suggest that the cytokines secreted by (Th1 or Th2) cells are responsible for various aspects of the immune response observed during infections. Thus, ‘inflammatory’ Th1 cells secrete pro-inflammatory cytokines that are associated with important roles in cellmediated immunity. For example, IFN-g activates macrophages which may then (i) exhibit enhanced antimicrobial activity in phagosomes, (ii) secrete IL-8, attracting immune cells to the site of infection, and (iii) secrete IL-12, promoting further development of the Th1 subset. Moreover, IFN-g can promote class switching to complement-fixing, opsonizing antibodies (human IgG1, IgG3; murine IgG2a). Th1 cytokines can e.g. upregulate expression of E selectins (see INFLAMMATION) and they can also upregulate MHC class II antigens. DELAYED HYPERSENSITIVITY is one manifestation of the characteristically cell-mediated Th1type immune response. Th2 cells are typically T-helper cells in ANTIBODY FORMATION. Th2 (anti-inflammatory) cytokines down-regulate macrophages and promote B cell activation, thus being important in the ‘humoral’ (antibody-mediated) immune response to infection by e.g. extracellular bacteria and helminths etc. IL-4 promotes class switching to non-complement-fixing IgG (human IgG4; murine IgG1) as well as to IgE in both man and mice. IL-5 promotes eosinophilia which may give activity against e.g. helminths and other parasites. IL-6 may contribute to antimicrobial activity by stimulating B cell proliferation and/or inducing ACUTE-PHASE PROTEINS. Therapeutic uses of cytokines. Because cytokines regulate so many aspects of the immune defence system they are attractive as candidate therapeutic agents; for example, INTERFERONS have been useful in various contexts. However, some cytokines (e.g. TNF), though potentially useful, may be unsuitable for therapy owing e.g. to instability or toxicity in vivo; interestingly, a non-toxic TNF-mimetic peptide has been found to prevent recrudescence of Mycobacterium bovis (BCG) infection in CD4+ T cell-depleted mice [JLB (2000) 68 538–544]. Inhibition of TNF-a can be achieved by monoclonal antibodies or by soluble TNF-a receptor molecules. [New perspectives on the design of cytokines and growth factors: TIBtech. (2000) 18 455–461.] [Molecular biology of the cytokines: Book ref. 226.] cytokinesis Those events, excluding nuclear division, which occur during the division of a eukaryotic cell into progeny cells; they include the apportionment of the cytoplasm and organelles, and may include e.g. synthesis of new material for the cell wall of each progeny cell. cytokinins (kinins, phytokinins) PHYTOHORMONES which stimulate metabolism and cell division; the cytokinins are 6-Nsubstituted adenines which are synthesized mainly at the root apex and translocated via the xylem. (Cytokinin-like activity is exhibited by certain urea derivatives, e.g. diphenylurea (found in coconut milk); it is believed that such compounds act by promoting the 6-N-substitution of endogenous adenine.) The mechanism by which cytokinins promote cell division is unknown; one suggestion is that cell division is encouraged by an increase in the level of endogenous cAMP brought about by the inhibition of cAMP phosphodiesterase by cytokinins. Compounds similar or identical to cytokinins are produced by certain microorganisms; such compounds may account for the formation of ROOT NODULES and for the development of symptoms in e.g. FASCIATION.

with the severity of disease [e.g. PNAS (2000) 97 8829–8835 (8833–8834)]. During infection with Yersinia, the pathogen’s secreted YopP/YopJ (see VIRULON) down-regulates the pro-inflammatory response – e.g. inhibiting the formation of both TNF-a and IL-8; the mechanism involves inhibition of the kinase that phosphorylates (and inactivates) IkBa, thus inhibiting transcription of NF-kB-dependent genes [PNAS (2000) 97 8778–8783 (8781–8782)]. Viruses may inhibit cytokines in various ways; for example, soluble forms of TNF and IL-8 receptors are encoded by Shope fibroma virus and CMV, respectively. (See also INTERLEUKIN-18.) (See also DISSEMINATED INTRAVASCULAR COAGULATION; DNA VACCINE; HAEMOPHAGOCYTIC SYNDROME; JARISCH–HERXHEIMER REACTION; LEPROSY; MODULIN; NITRIC OXIDE; P FIMBRIAE; SUPERANTIGEN; TOXIC SHOCK SYNDROME.) Many infections elicit an immunological response in which a particular subset of T LYMPHOCYTES – either Th1 or Th2 – is dominant. For example, Th1-type responses are typical in certain bacterial and protozoan infections, while Th2-type responses are common e.g. when infection involves helminths [IT (1996) 17 138–146]; moreover, in at least some cases, an ‘inappropriate’ response (e.g. Th2 instead of Th1) is associated with increased susceptibility to the infection. Naive CD4+ T cells (i.e. those not previously exposed to antigen) may develop as either Th1 or Th2 cells on exposure to antigen; the mechanism that selects one or other subset of T cells is unknown, but the decision to develop one way or the other is influenced by the microenvironment of cytokines which are present during activation of the T cell by antigen – e.g. IL-12 promotes the Th1 response, while IL-4 promotes differentiation to Th2 cells. (A newly reported cytokine receptor, designated TCCR, appears to be necessary for the Th1-type immune response in mice [Nature (2000) 407 916–920].) Interestingly, glucocorticoids from stress metabolism may suppress IL-12 (the main inducer of the Th1-type response); that is, stress-derived glucocorticoids may shift the balance of the immune response from Th1-type toward Th2-type [BCEM (1999) 13 583–595]. One important difference between Th1- and Th2-type responses is that Th1 and Th2 cells secrete different types of cytokine (see table) and so have correspondingly dissimilar physiological roles. (In this context, it is interesting to note that when the molecule ICAM-1 was co-expressed with antigen (on the antigen-presenting cell) the Th2 cytokine IL-4 was found CYTOKINES: some of the cytokines secreted by Th1 and Th2 subsets of T lymphocytes Cytokine

Th1

Interleukin-2 Interleukin-3 Interleukin-4 Interleukin-5 Interleukin-6 Interleukin-10 Interleukin-13 Interferon-g TNF-a TNF-b

+ +

a

+ + +

Th2 + + + + + + +a

Secretion from Th2 cells reported to be lower than that from Th1 cells. 216

cytoplasmic membrane Interestingly, cytokinins are incorporated in specificitydetermining positions in a small proportion of tRNA molecules. (See also KINETIN and ZEATIN.) cytolysin A toxin which lyses (usually eukaryotic) cells. cytolytic Able to lyse cells. cytolytic T cell See T LYMPHOCYTE. cytomegalic inclusion disease (CID) A disease caused by human cytomegalovirus (CMV) – see BETAHERPESVIRINAE. CMV can infect almost any tissue; infected cells are characteristically enlarged with large intranuclear inclusion bodies. Virus transmission occurs e.g. by direct contact, by transfusion of blood from an infected donor, or via the placenta. Congenital CID is commonly asymptomatic, but can be a severe condition with e.g. hepatosplenomegaly, encephalitis with irreversible CNS damage, and increased incidence of congenital deformities (see also TORCH DISEASES). Postnatal and adult infections are probably largely asymptomatic; in some cases the disease resembles INFECTIOUS MONONUCLEOSIS (‘CMV mononucleosis’, Paul–Bunnell test negative). In immunodeficient patients CMV infection may lead to e.g. pneumonia, transplant rejection, and/or death; infection may be primary or may result from reactivation of latent CMV. Patients at risk from CMV-related disease may be monitored by a NASBA-based assay of cytomegalovirus late gene UL65 (which encodes the pp67 protein) [JCM (1998) 36 1341–1346]; a commercial form of the assay for CMV was introduced by Organon Teknika. Known antiviral agents are not effective against CID. cytomegaloviruses See BETAHERPESVIRINAE. cytomegaly See CYTOPATHIC EFFECT. cytomembranes Syn. INTRACYTOPLASMIC MEMBRANES. cytomere A multinucleate structure which is formed by fragmentation of a schizont and which subsequently gives rise to merozoites. cytopathic effect (CPE) (virol.) A change or abnormality in cells due to virus infection. CPEs may include e.g. INCLUSION BODY formation, cytoplasmic vacuolation (see e.g. SPUMAVIRINAE), cell enlargement (cytomegaly) (see e.g. BETAHERPESVIRINAE), SYNCYTIUM formation (see e.g. PARAMYXOVIRUS), the formation of discrete foci of cell proliferation (see e.g. FRIEND VIRUS and MCF VIRUSES), cell death (see also PLAQUE), etc. The CPEs produced by a given virus in a given cell system are often characteristic and may be useful in the identification of the virus; some viruses characteristically fail to give rise to CPE even when viral replication occurs (see e.g. RUBIVIRUS). Cytophaga A genus of GLIDING BACTERIA of the CYTOPHAGALES; species occur in soil and in freshwater, estuarine and marine habitats. The organisms are rods or filaments, up to ca. 50 µm long, containing carotenoid pigments ranging from yellow to red; they are chemoorganotrophs and may be aerobic (respiratory metabolism using oxygen – or, in at least one strain, nitrate – as electron acceptor) or facultatively anaerobic (facultatively fermentative). Typically, Cytophaga spp can attack polysaccharides such as AGAR, ALGINATE, CELLULOSE and CHITIN. GC%: ca. 28–39. Cytophagaceae See CYTOPHAGALES. Cytophagales An order of GLIDING BACTERIA which do not form fruiting bodies (cf. MYXOBACTERALES); constituent species, all of which are Gram-negative, occur e.g. in soil and in freshwater, estuarine and marine habitats. In an early taxonomic scheme [Book ref. 21, pp. 99–119] four families were distinguished: motile rods or filaments containing carotenoid pigments (Cytophagaceae); motile filaments lacking carotenoid pigments (Beggiatoaceae); flat, non-pigmented, motile filaments found in

the oral cavity in vertebrates (Simonsiellaceae); non-pigmented filaments, attached (at one end) to other filaments or to the substratum, which form gliding gonidia (Leucotrichaceae). Genera include ALYSIELLA, BEGGIATOA, CYTOPHAGA, FLEXIBACTER, HERPETOSIPHON, LEUCOTHRIX, SAPROSPIRA, SIMONSIELLA, SPOROCYTOPHAGA, THIOPLOCA, THIOTHRIX and VITREOSCILLA. In another taxonomic scheme [ARM (1981) 35 339–364 – cf. FLEXIBACTERIAE], of the above genera only Cytophaga, Flexibacter and Sporocytophaga are included in the Cytophagales; the other genera are classified as apochlorotic cyanobacteria. cytopharyngeal apparatus (ciliate protozool.) Skeletal and certain other elements of the CYTOPHARYNX. Two main types of cytopharyngeal apparatus have been distinguished: the CYRTOS and the RHABDOS; this taxonomically important distinction is believed to reflect evolutionary differences in the different ciliate groups – those having a rhabdos-type structure being regarded as the more primitive. cytopharyngeal basket Syn. CYRTOS. cytopharynx (ciliate protozool.) An invagination of the cytoplasmic membrane which is supported, within the cytoplasm, by a tubelike system of microtubules and/or microfibrils. (See also CYTOPHARYNGEAL APPARATUS and CYTOSTOME.) Food particles which pass into the (non-ciliated) cytopharynx are taken up by PHAGOCYTOSIS through the cytoplasmic membrane at its inner end. cytophilic antibodies Antibodies which can bind to a cell surface without involving their COMBINING SITES; the bound antibody can therefore still bind homologous antigen. (See e.g. REAGINIC ANTIBODIES.) cytoplasmic genes (extrachromosomal genes; extranuclear genes) Genes which are not located on a bacterial CHROMOSOME or in a (eukaryotic) NUCLEUS; in eukaryotic organisms the term commonly refers to the genes in a CHLOROPLAST or a MITOCHONDRION, while in prokaryotes it has been used to refer to the genes carried by a PLASMID. (See also CYTOPLASMIC INHERITANCE.) cytoplasmic heterozygote See CYTOHET. cytoplasmic inheritance (extrachromosomal inheritance; nonMendelian inheritance) Inheritance governed or influenced by CYTOPLASMIC GENES – which are not subject to the Mendelian laws of segregation and assortment; see e.g. MATERNAL INHERITANCE. cytoplasmic membrane (CM; cell membrane; plasma membrane; plasmalemma; protoplast membrane) The lipid- and proteincontaining, selectively permeable membrane which encloses the cytoplasm in prokaryotic and eukaryotic cells; in most types of microbial cell the CM is bordered externally by the CELL WALL. In microbial cells the precise composition of the CM may depend on growth conditions and on the age of the cell. The structure of all biological membranes appears to conform to the basic fluid mosaic model. In this model the lipid molecules form a bilayer within which the protein molecules are partly or wholly embedded – some spanning the entire width of the bilayer; the lipid molecules are orientated such that their polar groups form the outer, hydrophilic surfaces of the bilayer while their hydrocarbon chains form the hydrophobic interior of the bilayer. (cf. UNIT MEMBRANE.) The membrane proteins are sometimes categorized as either peripheral (= extrinsic) proteins (bound to the membrane e.g. by electrostatic forces, and easily removable by electrolytes or chelating agents) or integral (= intrinsic) proteins (bound more strongly by hydrophobic bonds and extractable, with difficulty, by detergents or organic solvents). Cytoplasmic membranes are characteristically asymmetrical, i.e. the components of the outer (externally facing) 217

cytoplasmic membrane Lipid components of bacterial CMs are mainly phospholipids; in many or all cases, these are synthesized within the membrane itself. Phosphatidylglycerols (PG) appear to occur in all bacteria, while phosphatidylethanolamine (PE) is more common and more abundant in Gram-negative species; phosphatidylcholine is absent in Gram-positive cells and is rare in Gram-negative bacteria. Phosphatidylinositol occurs in some bacteria (e.g. Mycobacterium spp). PLASMALOGENS are found in the cytoplasmic membrane in some anaerobes. In Escherichia coli the main phospholipid is PE – PG and diphosphatidylglycerol (DPG, cardiolipin) being relatively minor components. Glycolipids are common in small quantities; in some Grampositive bacteria molecules of glycolipid may be covalently linked to glycerol TEICHOIC ACIDS, forming lipoteichoic acid. Sphingolipids are rare in bacterial membranes. Sterols are absent in most species (cf. MYCOPLASMATACEAE). Hopanes (triterpene derivatives which resemble sterols in size, rigidity and amphiphilicity) are present in some bacteria [JGM (1985) 131 1363–1367]. Lipoamino acids (O-aminoacylphosphatidylglycerols) occur in the membranes of some Gram-positive bacteria (e.g. Bacillus spp, Clostridium spp, Staphylococcus aureus). These are esters of PG and basic amino acids such as arginine, lysine or ornithine; the proportion of lipoamino acids varies according to growth phase and to the pH of the medium. The CM fatty acids may be straight-chained or branched (the latter more common in Gram-positive species), saturated or unsaturated; some contain a cyclopropane ring (which is formed by methylation at a double bond). Phospholipids often contain one saturated and one unsaturated fatty acid residue per molecule. In E. coli the main saturated fatty acids are hexadecanoic (palmitic) and tetradecanoic (myristic) acids, minor components including e.g. octadecanoic (stearic) and dodecanoic (lauric) acids; the main unsaturated fatty acids (all of which are cismonoenes) include e.g. cis-19 -hexadecenoic (palmitoleic) acid. In general, the CM varies in its fatty acid composition according to growth conditions (e.g. temperature, pH). Thus, in some species the proportion of unsaturated fatty acids increases when the growth temperature decreases – e.g. in E. coli the proportion of unsaturated fatty acids increases from 16% to 49% when the growth temperature falls from 36° C to 25° C; such a change appears to be a compensatory response which helps to maintain optimum membrane fluidity. In contrast, almost no increase in monoenoic fatty acids occurs in the CM of Staphylococcus aureus when the growth temperature drops from 37° C to 25° C [Book ref. 44, p 402]. In some bacteria, adaptation to lower growth temperatures involves an increase in the length of fatty acid chains rather than an increase in the degree of unsaturation [JGM (1985) 131 2293–2302]. The lipids of the CM clearly contribute to the essential feature of selective permeability. However, the lipids also have other functions; for example, in E. coli phosphatidylethanolamine can behave as a ‘molecular chaperone’, being required for the correct folding (maturation) of the membrane protein LacY [EMBO (1998) 17 5255–5264]. Proteins in the bacterial CM include a variety of enzymes (involved e.g. in the synthesis of phospholipids and cell wall components); for example, penicillin-binding proteins (involved in the synthesis of PEPTIDOGLYCAN) may form part of a protein complex in the CM [FEMS Reviews (1994) 13 1–12]. There are also components of TRANSPORT SYSTEMS, energy-converting

side of the membrane are not identical to those of the inner (cytoplasmic) side. Membrane ‘fluidity’ primarily involves lateral and rotational motion of whole lipid molecules as well as motion of the hydrocarbon chains of the lipid molecules (rather than movement of whole lipid molecules from one layer of the membrane to the other layer). The hydrocarbon chains may be disordered and flexible (the a-conformation) or ordered, rigid and perpendicular to the plane of the bilayer (the b-conformation). Fluidity greater than a certain level is essential for the normal physiological role of the CM. The degree of fluidity is governed by temperature and e.g. by the length and structure of the hydrocarbon chains; membranes containing unsaturated chains are generally more ‘fluid’ than are membranes containing saturated chains of the same length. Previously, it was thought that only rarely do lipid molecules move from one side of the bilayer to the other. It is now known that such transmembrane movement (flip–flop) occurs with a much greater frequency than was originally supposed; in at least one case evidence has been obtained for a ‘flippase’ which may facilitate such translocation [Cell (1985) 42 51–60]. Although it is believed that the membrane lipids are normally present as a bilayer, results of nuclear magnetic resonance (NMR) and other studies have indicated the presence of transient, temperature-dependent, localized non-bilayer lipid phases within biological membranes. In one of these phases, termed hexagonal II (or HII ), the lipid molecules form an array of fine ˚ diam.) water-filled cylinders whose walls are composed (∼20 A of the polar heads of lipid molecules; the array of cylinders is hexagonal in cross-section, the space between the cylinders containing the hydrocarbon chains of the lipid molecules. [Lipid structure of biological membranes: TIBS (1985) 10 418–421.] The CM has various functions, one of which is to regulate the cytoplasmic milieu by controlling the inward and outward passage of ions and molecules. Some uncharged and/or lipophilic molecules can pass relatively freely through the CM; these include e.g. water, carbon dioxide, oxygen, ammonia (but not ammonium ions), acetic acid (undissociated form) and ethanol. However, ions and most molecules cannot pass freely through the CM, so that their transmembrane translocation requires more or less specific TRANSPORT SYSTEMS. (Specific mechanisms also exist for OSMOREGULATION.) Transport commonly occurs at the expense of metabolic energy, and some systems depend on the presence of a transmembrane electrochemical gradient – e.g. proton motive force (pmf: see CHEMIOSMOSIS) or SODIUM MOTIVE FORCE – such gradients being a general feature of CMs. According to species, the CM is also the site of RESPIRATION (and, in some organisms, photosynthesis). The CM is involved in the synthesis of external structures, such as the cell wall and capsule, and also in the synthesis of components of the CM. (a) Bacterial cytoplasmic membranes. In transmission electron micrographs the CM, ca. 7–8 nm thick, typically appears as a trilaminar structure: an electron-translucent layer sandwiched between two electron-dense layers. In Gram-negative bacteria, localized regions of the CM may be involved in ADHESION SITES. In many species of bacteria it has been demonstrated that the inner (cytoplasmic) face of the CM bears minute, spherical, ‘stalked’ particles (see PROTON ATPASE) which are involved in energy conversion. In many (not all) species, CYTOCHROMES and other components of an ELECTRON TRANSPORT CHAIN occur in the CM. (See also PURPLE MEMBRANE.) 218

cytoskeleton systems (see e.g.

and EXTRACYTOand sensing systems (see e.g. CHEMOTAXIS). CM proteins also include the molecular water channels called aquaporins (see MIP CHANNEL). (See also MECHANOSENSITIVE CHANNEL.) [Structural dynamics of the CM of E. coli : Book ref. 122, pp 121–160.] The bacterial CM is the target for a variety of ANTISEPTICS and DISINFECTANTS (see e.g. QUATERNARY AMMONIUM COMPOUNDS) and ANTIBIOTICS (see e.g. DEPSIPEPTIDE ANTIBIOTICS, GRAMICIDINS, POLYMYXINS and TYROCIDINS). (b) Fungal cytoplasmic membranes. The CMs in fungi (and in other eukaryotes) differ significantly from those in bacteria. In fungal CMs the major lipids typically include phosphatidylcholine and phosphatidylethanolamine (with smaller amounts of phosphatidylinositol and phosphatidylserine) together with SPHINGOLIPIDS; as a rough generalization, the fatty acids of phospholipids in higher fungi tend to contain even numbers of carbon atoms and to be saturated or mono-unsaturated, while those of lower fungi tend to have odd numbers of carbon atoms and to be polyunsaturated. (Changes in the degree of fatty acid saturation can have interesting physiological effects; for example, when Saccharomyces cerevisiae strain Y185 becomes de-repressed for general amino acid permease, a higher degree of fatty acid unsaturation in the CM correlates with a more rapid expression of the permease [JGM (1985) 131 57–65].) Most fungal membranes also contain sterols (e.g. ergosterol), so that fungi are generally susceptible to POLYENE ANTIBIOTICS (see also AZOLE ANTIFUNGAL AGENTS); vegetative cells of members of the Pythiaceae have been reported to lack sterols, although sterols are required during the reproductive phase. Proteins in fungal CMs include those involved in transport processes, components of ATPase complexes, and various enzymes – such as those needed for the synthesis of walls and membranes. In addition to lipids and proteins, fungal CMs contain small amounts of carbohydrate. In e.g. some slime moulds, certain CM carbohydrates are important LECTIN receptors and are involved in cell–cell recognition and/or adhesion. (c) Archaeal cytoplasmic membranes. In members of the ARCHAEA the CM contains lipids of a kind which do not occur in bacteria. Unlike the ester-linked glycerol–fatty acid bacterial lipids, archaeal lipids are characteristically ether-linked molecules that contain e.g. isoprenoid or hydro-isoprenoid components. Some of the archaeal lipids are structurally analogous to those of bacteria; for example, the di-ether and di-ester lipids both have a single polar end. However, some archaeal lipids (e.g. tetra-O-di(biphytanyl) diglycerol) contain one ether-linked glycerol residue at each end of the molecule; having two polar ends, such molecules may span the width of the CM. Given the exteme habitats typically occupied by these organisms, it seems likely that some or all of the archaeans will be found to contain membrane components whose characteristics reflect an adaptation to the environment. Some archaeans contain MIP CHANNELS. cytoplasmic petite See PETITE MUTANT. cytoplasmic polyhedrosis virus group (CPV group; Cypovirus) A genus of entomopathogenic viruses of the REOVIRIDAE. Genome: 10 dsRNA molecules which may be linked together by protein in the virion. CPVs are pathogenic in a wide range of insects of the Diptera, Hymenoptera and Lepidoptera, and can also infect certain crustaceans (Simocephalus expinosus); the type member, a CPV from the silkworm (Bombyx mori ),

has caused significant economic losses in the silk industry. A CPV is commercially available in Japan for the BIOLOGICAL CONTROL of the pine caterpillar Dendrolimus spectabilis. (cf. BACULOVIRIDAE; see also INSECT DISEASES.) CPV infection is usually chronic and is generally restricted to the columnar epithelial cells of the midgut. The mature virions occur embedded in POLYHEDRA in the cytoplasm of infected cells (cf. NUCLEAR POLYHEDROSIS VIRUS). The polyhedra may be polyhedral, cuboid, triangular etc, depending on virus and host. The infected insect shows symptoms of starvation due to reduced feeding and a reduction in the absorptive capacity of the gut cells; diarrhoea is common, with large numbers of polyhedra in the faeces. Infected larvae commonly reach adulthood, but the adults are generally small and often malformed, with greatly diminished reproductive capacity. CPVs are apparently transmitted to the larvae via the surface of the egg. [Review: Book ref. 83, pp. 425–504.] cytoplasmic streaming (cyclosis) The intracellular flow of protoplasm which occurs in various types of eukaryotic cell; such a flow ensures e.g. that intracellular reactions are not dependent on simple diffusion. In e.g. the green alga Chara, cytoplasmic streaming appears to result from the interaction between peripheral ACTIN microfilaments and MYOSIN, the relative movement between actin and myosin being reflected in the flow of cytosol and organelles. In amoebae, the characteristic amoeboid movement may involve local actin–myosin-mediated contractions in the cell cortex accompanied by cytoplasmic streaming due to gel–sol interconversions in the microfibrillar networks. cytoplast A eukaryotic cell from which the nucleus has been removed (i.e., an ENUCLEATED CELL). (cf. KARYOPLAST.) cytoproct (cytopyge) In some protozoa: a permanent pore through which is voided particulate non-digestible material. cytopyge Syn. CYTOPROCT. cytosegresome An intracellular, membrane-limited vacuole within which a cell has enclosed some of its own constituents. Cytosegresomes are formed during AUTOPHAGY. cytosine arabinoside Syn. CYTARABINE. cytoskeleton In a eukaryotic cell: the framework, composed primarily of proteinaceous tubules and fibrils, which ramifies throughout the cytoplasm (binding e.g. to the cytoplasmic membrane and to various organelles) and which is responsible e.g. for the shape and internal organization of the cell, the intracellular transport of vesicles and organelles, and (where applicable) cell motility; in a living cell the cytoskeleton probably undergoes continual modification – being disassembled in some regions and reassembled in others, according to the needs of the cell. (cf. NUCLEOSKELETON.) The main structural components of the cytoskeleton are microfilaments (see ACTIN), MICROTUBULES, and INTERMEDIATE FILAMENTS. Microtubules contribute e.g. to cell shape, to the correct location and orientation of intracellular structures and organelles, to certain types of motility (see e.g. axoneme in FLAGELLUM (b)), and to the formation of the spindle in MITOSIS; they can also serve as a temporary scaffolding e.g. during intracellular rearrangements. [Role of microtubules during the cell cycle in Stephanopyxis turris: JCB (1986) 102 1688–1698.] Microfilaments are involved e.g. in those parts of the cytoskeleton concerned with intracellular movements (see e.g. CYTOPLASMIC STREAMING), amoeboid movement (see PSEUDOPODIUM), PHAGOCYTOSIS, and CAPPING (sense 3). Intermediate filaments may e.g. fulfil a strengthening role. There is some evidence that, in multicellular organisms and tissues, cytoskeletal elements may extend from one cell to another by penetrating cytoplasmic membranes and the intercellular matrix.

ELECTRON TRANSPORT CHAIN

PLASMIC OXIDATION)

219

cytosol [Molecular biology of the cytoskeleton: Book ref. 166; in vitro translocation of organelles along microtubules: Cell (1985) 40 729–730; reviews: JCS (1986) Supplement 5; the cytoskeleton in protists: Int. Rev. Cytol. (1986) 104 153–249.] cytosol The fluid (non-particulate) fraction of cytoplasm. (cf. CELL SAP; HYALOPLASM.) cytostome In certain protozoa (including many ciliates and some others, e.g. Noctiluca, Peranema): the cell mouth, a specific region of the cell through which particulate food is ingested. (See also AMOEBOSTOME.) In ciliates the cytostome is regarded as a two-dimensional aperture at the level of the PELLICLE; in this region the pellicle lacks both cilia and pellicular alveoli, and is typically invaginated within a supportive collar or tube-like structure of microtubules and/or microfibrils in the cytoplasm (see also CYTOPHARYNX and CYTOPHARYNGEAL APPARATUS). In advanced ciliates (e.g. Paramecium) that part of the pellicle which includes the

cytostome typically occurs at the base of a concavity in the body (BUCCAL CAVITY); in the more primitive ciliates (e.g. the gymnostomes) the cytostome-containing region of the pellicle is typically not recessed in this way, and is characteristically situated apically or subapically in the cell. In some ciliates the ciliature surrounding the cytostome is readily distinguishable from the somatic ciliature (see e.g. AZM and PARORAL MEMBRANE). cytotaxin Any agent chemotactic for cells. cytotoxic hypersensitivity Syn. TYPE II REACTION. cytotoxic T cell See T LYMPHOCYTE. cytotropism See TROPISM (sense 2). cytozoic Living (parasitic) within cells. Cyttariales See ASCOMYCOTINA. Czapek–Dox medium (Czapek’s medium) A medium containing sucrose, NaNO3 , K2 HPO4 , MgSO4 , KCl and FeSO4 ; it may be solidified with agar. It is used for culturing e.g. saprotrophic fungi, soil bacteria etc.

1. Words in SMALL CAPITALS are cross-references to separate entries. 2. Keys to journal title abbreviations and Book ref. numbers are given at the end of the Dictionary. 3. The Greek alphabet is given in Appendix VI. 4. For further information see ‘Notes for the User’ at the front of the Dictionary.

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Dictionary of Microbiology and Molecular Biology, Third Edition Paul Singleton and Diana Sainsbury © 2006 John Wiley & Sons Ltd. ISBN: 0-470-03545-5

D D

(1) Dihydrouridine (see

TRNA).

(2) Aspartic acid (see

carotenoid pigments. Genera include CALOCERA, Cerinomyces, DACRYMYCES, Dacryopinax, Guepiniopsis. Dacryopinax See DACRYMYCETALES. dactinomycin Syn. ACTINOMYCIN D. Dactylaria See HYPHOMYCETES; see also NEMATOPHAGOUS FUNGI and PHAEOHYPHOMYCOSIS. Dactylella See HYPHOMYCETES and NEMATOPHAGOUS FUNGI. Dactylococcopsis A genus of unicellular CYANOBACTERIA in which the cells are elongate with tapering ends, sometimes occurring in short chains. D. salina is a gas-vacuolate species which is blue-green when grown at low light intensities but deep orange under high light intensities; it is planktonic in hypersaline environments. Although sensitive to concentrations of H2 S > ca. 10 µM, at lower concentrations D. salina is capable of limited anoxygenic photosynthesis using H2 S as electron donor. [Ecophysiology of D. salina: JGM (1983) 129 1849–1856.] Dactylosoma See PIROPLASMASINA. Dactylosporangium A genus of mycelial bacteria (order ACTINOMYCETALES, wall type II) which occur e.g. in soil. The organisms form finger-like sporangia each containing a single row of three or more zoospores; non-motile spores are also formed, singly, on the substrate mycelium. Aerial mycelium is not formed. Type species: D. aurantiacum. Dactylostoma See SUCTORIA. DAEC See ENTEROADHERENT E. COLI. Daedalea A genus of fungi of the APHYLLOPHORALES (family Polyporaceae) which occur as perthotrophs (PERTHOTROPH sense 2) and saprotrophs on various types of wood. Basidiocarp: non-stipitate, often hoof-like, commonly corky, the upper surface brown to grey-brown; hymenophore: labyrinthiform (‘mazelike’), consisting of elongated pores with thick dissepiments. D. quercina, which grows e.g. on oak, may form imbricated basidiocarps with a trimitic context; basidiospores: ellipsoidal, hyaline, ca. 6 × 3 µm. (See also WOOD WASP FUNGI.) DAF See CD55. dahlia mosaic virus See CAULIMOVIRUSES. dairy products Many dairy products are made by a LACTIC ACID FERMENTATION of milk using selected strains of lactic acid bacteria (see e.g. LACTIC ACID STARTERS): see ACIDOPHILUS MILK; BUTTER; BUTTERMILK; CHEESE-MAKING; KEFIR; KOUMISS; LEBEN; QUARG; SOUR CREAM; TAETTE; VILIA; YOGHURT. (See also MILK.) daisy head colonies Colonies of the type commonly formed by Corynebacterium diphtheriae (gravis type) on blood–tellurite agar; after 24 hours at 37° C, each colony is 2–3 mm in diameter, dull, with a grey to black centre, translucent margin, crenated edge, and radial striations. Dakin’s solution (chlorinated soda solution) A solution of sodium hypochlorite and sodium bicarbonate used e.g. as an antiseptic for the cleansing of wounds. Daldinia A genus of fungi (order SPHAERIALES). D. concentrica grows on dead or fallen branches of certain trees, particularly ash (Fraxinus), forming hemispherical or subglobose, superficial stromata ca. 2–10 cm across; when young, each stroma has a surface layer of branched conidiophores bearing brown conidia, but the mature stroma is a hard, brittle, shiny black structure which, in vertical cross-section, exhibits alternating light and dark bands concentric about the centre of the base of the stroma. Perithecia develop in the superficial layer of the stroma with their

AMINO

ACIDS).

D (in continuous culture) DILUTION RATE. d-factor See DUTCH ELM DISEASE. D loop (mol. biol.) (1) (displacement loop) A single-stranded loop formed when a short ssDNA molecule pairs with a complementary region of one strand of a dsDNA molecule, displacing the corresponding region of the homologous strand (the D loop). For example, under certain (non-physiological) conditions in vitro a negatively supercoiled ccc dsDNA molecule can spontaneously take up a short complementary single (linear) strand to give rise to a D loop in a reaction driven by the energy of supercoiling; the resulting ‘joint molecule’ is more relaxed than the original supercoiled DNA. D-loop formation is promoted e.g. by the RECA PROTEIN; it may occur e.g. during RECOMBINATION (Fig. 2), and may be involved in the priming of certain types of DNA replication (see e.g. BACTERIOPHAGE G4). (See also SITE-SPECIFIC MUTAGENESIS; cf. R LOOP.) (2) The loop of the ‘D arm’ in a tRNA molecule (see TRNA). D period See HELMSTETTER–COOPER MODEL. 12D process In food processing: heating, at a given temperature, for a period equal to twelve times the D VALUE at that temperature. (See also BOTULINUM COOK.) D-type particles See TYPE D RETROVIRUS GROUP. D-type starter See LACTIC ACID STARTERS. D value (1) (D10 value; decimal reduction time) The time required, at a given temperature, to reduce the number of viable cells or spores of a given microorganism to 10% of the initial number; it is usually quoted in minutes. The temperature (° C) at which the D value is determined may be indicated by a subscript, e.g., D112 . (In the synonym of D value, D10 value, the subscript refers to the 10% survival value.) (cf. F0 VALUE; Z VALUE; see also 12D PROCESS.) (2) (of animal feed) The percentage of digestible organic matter in the ‘dry matter’ (DM) – DM (in g/kg) being determined by oven-drying of feed samples and correction for e.g. loss of volatile fatty acids. (See also SILAGE.) D10 value Syn. D VALUE (1). Da DALTON. dacA gene See PENICILLIN-BINDING PROTEINS. dacB gene See PENICILLIN-BINDING PROTEINS. dacC gene See PENICILLIN-BINDING PROTEINS. Dacrymyces A genus of fungi (order DACRYMYCETALES). D. deliquescens forms bright orange, gelatinous, globular asexual fruiting bodies (each up to ca. 5 mm diam.) on decaying wood; each fruiting body consists of a mass of radiating hyphae which, at the surface, break up into oidia. Subsequently, basidia develop at the surface of the same fruiting body, which concurrently becomes yellow. Dacrymycetales An order of typically lignicolous fungi (subclass HOLOBASIDIOMYCETIDAE) which form the so-called ‘tuning fork’ type of basidium – i.e., a two-spored basidium which is apically bifurcate (forked) and Y-shaped, the two arms of the ‘Y’ (the sterigmata) curving inwards to become more or less parallel. The basidiocarp may be e.g. crust-like, pulvinate, cuplike and stipitate, or columnar and branched or unbranched; it may be gelatinous or waxy, and in many species it is brightly coloured (e.g. yellow, orange) due, apparently, to 221

Dalmau plate technique ostiolar pores at the surface. The bulk of the stromal tissue may act as a reservoir for water. (See also ASCOSPORE.) Dalmau plate technique A technique used e.g. for studying the formation of pseudomycelium or true mycelium by a yeast. A streak and two point-inoculations of the test strain are made at well-separated locations on a surface-dried plate of e.g. CORNMEAL AGAR; the centre of the streak and one of the pointinoculations are then each overlaid with a sterile cover-glass. After incubation at 25° C for ca. one week the preparation is examined under the microscope. Dalmeny disease A disease of cattle which results in e.g. abortion or death; the causal agent is believed to be a species of SARCOCYSTIS. dalton (Da) Syn. ATOMIC MASS UNIT. Dalyellia viridis See ZOOCHLORELLAE. Dam-directed mismatch repair See MISMATCH REPAIR. dam gene In e.g. Escherichia coli : a gene which encodes a DNA adenine methylase (Dam methylase), i.e. an enzyme that methylates DNA at the N-6 position of adenine in the nucleotide sequence 5′ -GATC-3′ (‘Dam site’); a strand of DNA is methylated soon after its synthesis (see DNA METHYLATION). Dam methylation is involved e.g. in MISMATCH REPAIR in E. coli. It is also involved in regulating certain genes. For example, transposition of the transposon Tn10 (q.v.) is inhibited by Dam methylation of a sequence in the transposase gene promoter (reducing transposase synthesis) and of a sequence in IS10 (reducing transposase activity); Tn10 transposition is thus apparently coupled to DNA replication: it occurs just after the replication fork has passed but before Dam methylation has occurred. Other genes which contain Dam sites in their promoters, and whose expression is sensitive to Dam methylation, include e.g. the trpR gene of E. coli, the cre gene of BACTERIOPHAGE P1, and the mom gene of BACTERIOPHAGE MU. The chromosomal origin, oriC, in E. coli contains more than 10 Dam sites which may be important in regulating the initiation of DNA replication (see CELL CYCLE (b)). [Minireview: JB (1985) 164 490–493.] Dam methylation apparently occurs in various other Gramnegative bacteria (including certain cyanobacteria) and in some members of the Archaea. Dam methylation See DAM GENE. damping off (plant pathol.) A microbial disease of seedlings in which e.g. roots may rot, or the hypocotyl (lower stem) may either collapse or become wiry (‘wire stem’); seedlings may die before or after they emerge from the soil (pre-emergence and post-emergence damping off, respectively). Common causal agents include species of PYTHIUM and RHIZOCTONIA. Aerial parts are often secondarily affected by GREY MOULD. Damping off may be controlled e.g. by CARBENDAZIM, CHESHUNT COMPOUND, CHLORONEB or ETRIDIAZOLE. (cf. FOOT-ROT (sense 2) and BLACKLEG (sense 2).) Dane particle See HEPATITIS B. Danielli–Davson model See UNIT MEMBRANE. Danish agar Syn. FURCELLARAN. danofloxacin See QUINOLONE ANTIBIOTICS. dansyl chloride A reagent, 5-(dimethylamino)naphthalene-lsulphonyl chloride, which reacts with amino acids and proteins to form derivatives that exhibit an intense yellow fluorescence under UV irradiation. Danysz’ phenomenon The phenomenon in which the residual toxicity in a mixture of diphtheria toxin and antitoxin varies according to the method of admixture. Thus, if toxin is added to

an equivalent amount of antitoxin in one stage (i.e., all at once) the resulting mixture is non-toxic; however, if the same quantity of toxin is added in two halves (the second ca. 30 min after the first), the resulting mixture contains free (non-neutralized) toxin. In the second method of admixture, the first portion of toxin combines with more than its equivalent of antitoxin – leaving insufficient free antitoxin to neutralize the second portion of toxin. DAP pathway DIAMINOPIMELIC ACID PATHWAY. DAPI 4′ ,6-Diamidino-2-phenylindole: a FLUOROCHROME used e.g. as a DNA-specific stain. [Limn. Ocean. (1980) 25 948–951.] (See also DIAMIDINES.) dapsone (DDS) A drug used e.g. in the treatment of LEPROSY and MALARIA: 4,4′ -diaminodiphenylSULPHONE; DDS may inhibit FOLIC ACID metabolism. [Book ref. 54, p. 422.] (cf. CLOFAZIMINE.) daptomycin A lipopeptide antibiotic which, in vitro, is bactericidal for a range of clinically important Gram-positive bacteria, including e.g. MRSA and vancomycin-resistant enterococci (VRE); daptomycin apparently interferes with the function of the bacterial cytoplasmic membrane. [Resistance studies with daptomycin: AAC (2001) 45 1799– 1802.] dark-field microscopy See MICROSCOPY (b). dark-ground microscopy See MICROSCOPY (b). dark mildews Syn. BLACK MILDEWS. dark reaction See PHOTOSYNTHESIS. dark repair (1) Light-independent DNA REPAIR: e.g. EXCISION REPAIR or RECOMBINATION REPAIR (as opposed to PHOTOREACTIVATION). (2) Syn. EXCISION REPAIR. Darling’s disease Syn. HISTOPLASMOSIS. Darmbrand ENTERITIS NECROTICANS. dasycladalean algae A small group of tropical and subtropical marine green algae (division CHLOROPHYTA) which typically grow in shallow waters. The vegetative thallus is uninucleate and is radially symmetrical, composed of an erect axis with whorls of branches and a rhizoid-like holdfast which contains the nucleus; the thallus becomes multinucleate during gametangial development. Fossil dasyclads are known from the Lower Palaeozoic onwards [Book ref. 123, pp. 297–302]; modern genera include ACETABULARIA. Dasyscyphus See HELOTIALES. Dasyspora See UREDINIOMYCETES. Dasytricha A genus of ciliates (order TRICHOSTOMATIDA) which occur e.g. in the RUMEN. Cells: ovoid, with dense, uniform somatic ciliature and a cytostome located posteriorly. DAT (serol.) Differential agglutination test: any in vitro diagnostic test in which the result consists of two agglutination titres – that of the test proper and that of the control; the titres may be quoted in full or expressed as a ratio. daughter-strand gap repair See RECOMBINATION REPAIR. daunomycin See ANTHRACYCLINE ANTIBIOTICS. daunorubin See ANTHRACYCLINE ANTIBIOTICS. Davson–Danielli model See UNIT MEMBRANE. dazomet A soil fumigant (3,5-dimethyltetrahydro-2H-1,3,5thiadiazine-2-thione) used as a fungicide and nematocide; in soil it breaks down to form e.g. formaldehyde and N-methylisothiocyanate. (cf. METHAM SODIUM.) DBMIB An inhibitor of PHOTOSYNTHESIS. Dc Critical DILUTION RATE. DCA (deoxycholate–citrate agar) An agar medium used for the primary isolation of e.g. Salmonella and Shigella; most strains of Escherichia and of the Proteeae (cf. PROVIDENCIA) fail to grow on DCA. DCA generally contains meat extract, peptone, lactose, 222

defective interfering particle sodium citrate, ferric ammonium citrate, sodium deoxycholate, and neutral red; pH ca. 7.3. DCA should not be sterilized by autoclaving. DCCA See DICHLOROISOCYANURATE. DCCD N,N ′ -Dicyclohexylcarbodiimide; under weakly alkaline conditions DCCD binds covalently to the ‘DCCD-binding protein’ of F0 in (F0 F1 )-type H+ -ATPases and inhibits both the synthesis and hydrolysis of ATP, while under weakly acidic conditions it binds to the b subunit of F1 , inhibiting the hydrolysis of ATP. DCDS See CONJUGATION (1b) (i). DCMU (Diuron) N-(3,4-dichlorophenyl)-N ′ -dimethylurea; this agent acts as a mitochondrial RESPIRATORY INHIBITOR, blocking electron flow between cytochromes b and c1 in Complex III of the ELECTRON TRANSPORT CHAIN (cf. BAL), and as an inhibitor of electron flow between photosystems I and II (see PHOTOSYNTHESIS). dda gene (in bacteriophage T4) See HELICASES. DDMR See MISMATCH REPAIR. DDS DAPSONE. ddTTP 2′ ,3′ -Dideoxythymidine triphosphate: an analogue of thymidine triphosphate; it inhibits DNA synthesis since, when incorporated in a growing DNA strand in place of thymidine, it provides no 3′ -OH for further polymerization. In mammalian cells it specifically inhibits DNA polymerase b action; the a enzyme is apparently unable to incorporate the analogue in a growing DNA strand. (cf. APHIDICOLIN.) de-acetylase See ANTIBIOTIC. dead man’s fingers See XYLARIA. Dean and Webb titration A serological titration in which a constant volume of a given antiserum is added to each of a number of serial dilutions of the homologous antigen; precipitation occurs most rapidly in that dilution in which antibody and antigen are present in OPTIMAL PROPORTIONS. death cap fungus See AMANITA. death phase See BATCH CULTURE. death rate constant See STERILIZATION (b). Debaryomyces A genus of yeasts (family SACCHAROMYCETACEAE) which reproduce by multilateral budding; pseudomycelium may be formed. Ascus formation is generally preceded by conjugation between bud and mother cell; conjugation between separate cells also occurs. Ascospores: spherical or oval, minutely warty or ridged, usually 1 or 2 (up to 4 in some species) per ascus. Fermentation occurs (weakly) in some species. NO3 − is not assimilated. Species (D. castellii, D. coudertii, D. hansenii, D. marama, D. melissophilus, D. polymorphus, D. pseudopolymorphus, D. tamarii, D. vanriji ) have been isolated from soil, foods etc. [Book ref. 100, pp. 130–145.] debranching enzyme (1) (amylo-1,6-glucosidase) An enzyme which hydrolyses the (1 → 6)-a branch points in e.g. amylopectin, glycogen, and/or related polysaccharides. There are two types: pullulanase (‘limit dextrinase’, pullulan 6-glucanhydrolase, EC 3.2.1.41), which can degrade PULLULAN, and isoamylase (glycogen 6-glucanhydrolase, EC 3.2.1.68), which has no action on pullulan. Pullulanases are obtained commercially from e.g. Klebsiella aerogenes (‘Aerobacter aerogenes’) and Bacillus cereus var. mycoides; the enzyme from K. aerogenes can debranch amylopectin and its b-limit dextrin (see AMYLASES) but has little or no activity on native glycogen, while that from B. cereus var. mycoides has little or no activity on amylopectin but can degrade its b-limit dextrin [Book ref. 31, pp. 133–137]. Isoamylases are obtained e.g. from Pseudomonas sp. (cf. BRANCHING ENZYME.)

(2) (mol. biol.) An enzyme which ‘debranches’ the lariat form of an excised intron (see SPLIT GENE). d´ebridement The removal of necrotic/infected tissue and/or foreign material from a wound. debromoaplysiatoxin See LYNGBYA. decarboxylase tests Tests used to determine the ability of a given bacterial strain to decarboxylate arginine, lysine and/or ornithine. Three tubes of MØLLER’S DECARBOXYLASE BROTH, each containing one of the three amino acids, are inoculated with the test organism; each broth is overlaid with a layer of sterile paraffin, incubated at 37° C, and examined daily for 4 days. Initially, in both positive and negative tests, glucose is metabolized to acidic products causing the pH indicator bromcresol purple (in the medium) to turn yellow. In a positive test the amino acid is cleaved by a specific decarboxylase in a reaction requiring pyridoxal phosphate (see PYRIDOXINE); the product is a polyamine (see POLYAMINES) which raises the pH of the medium, causing bromcresol purple to turn purple. Arginine, lysine and ornithine are decarboxylated to agmatine, cadaverine and putrescine, respectively. decay-accelerating factor See CD55. Dechloromonas See BIOREMEDIATION. Dechlorosoma See BIOREMEDIATION. decimal code (for growth stages of cereals) See ZADOKS’ CODE. decimal reduction time Syn. D VALUE (1). declomycin See TETRACYCLINES. decoy receptor See e.g. INTERLEUKIN-1. decoyinine See PSICOFURANINE. decurrent (mycol.) Refers to hymenium-bearing structures (e.g. lamellae in agarics, the layer of ‘teeth’ in Hydnum) whose region of attachment to the fruiting body extends at least partly down the stipe. Dee disease See KIDNEY DISEASE. deep (noun) (1) Any solid medium present (in a tube) at a depth sufficient to permit stab inoculation. (2) A SHAKE CULTURE (sense 1). deep rough mutant See SMOOTH–ROUGH VARIATION. defaunation The removal of the fauna (animal life) from a given environment – especially the removal of protozoa from a mixed microbial population (e.g. that of the RUMEN). defective interfering particle (DI particle; defective interfering virus) A DEFECTIVE VIRUS which typically arises as a result of mutation (usually deletion mutation) in an originally nondefective virus (the standard virus); a DI particle can replicate only in the presence of the standard virus, and its presence reduces the yield of infectious standard virus (i.e., it exhibits INTERFERENCE). (The preferential production of DI particles at the expense of standard virus is known as enrichment.) The generation of DI particles and their ability to cause interference depend, at least to some extent, on the nature of the host cell. The mechanisms of DI particle generation, enrichment and interference are poorly understood. [Primary structure of poliovirus DI particle genomes and possible mechanism for their generation: JMB (1986) 192 473–487.] DI particles commonly accumulate in stocks of animal viruses which have been passaged at high multiplicity of infection (moi). (Passage at low moi minimizes the chances of a cell being coinfected with both DI and standard viruses, so that any DI particles which arise are unlikely to be able to replicate.) DI particles can attenuate the pathological effects of a virulent standard virus (and in some cases of other closely related viruses) both in cell cultures and in animals under experimental conditions; however, the presence of DI particles may also allow 223

defective virus the establishment of a persistent infection of cells or animals by a virus which does not normally exhibit PERSISTENCE [e.g. Semliki Forest virus in mice: JGV (1986) 67 1189–1194]. The role of DI particles – if any – in attenuating disease or in establishing persistent infections under natural conditions is unknown. defective virus A virus which – inherently or e.g. as a result of mutation – lacks one or more genetic functions necessary for its replication; such a virus can produce progeny in the presence of another (non-defective) HELPER VIRUS which can provide the missing functions. (See also e.g. DEFECTIVE INTERFERING PARTICLE; RETROVIRIDAE; SATELLITE VIRUS; TRANSDUCTION.) defensins PEPTIDE ANTIBIOTICS, produced e.g. by mucosal epithelial cells and macrophages, which are active against a range of bacteria, including both Gram-positive and Gram-negative species; examples: the tracheal antimicrobial peptide found in bovines, cryptdin in mice, and human neutrophil peptide. [See e.g. Nature (2003) 422 522–526.] defined medium See MEDIUM. definitive host Syn. FINAL HOST. DEFT Direct epifluorescent filter technique: a technique used e.g. for the rapid detection and/or quantification of microorganisms in water, milk etc. Essentially, the sample is passed through a membrane filter (see FILTRATION), and the cells retained on the filter are counted by epifluorescence MICROSCOPY – the cells having been stained with a fluorescent dye either before or after filtration. For the examination of MILK, the sample is pretreated with a protease (e.g. trypsin) and a detergent (e.g. Triton X100) to disrupt, respectively, the casein micelles and fat globules which would otherwise block the membrane filter. degeneracy (mol. biol.) See GENETIC CODE. degerming Syn. ANTISEPSIS. DegP protease See FIMBRIAE (P fimbriae). degradosome In Escherichia coli : a multicomponent complex which includes RNASE E and certain other proteins involved in the degradation/processing of RNA molecules; degradosomes are associated with the cytoplasmic membrane of the cell via the N-terminal part of RNase E. Proteins which have been identified in degradosomes include polynucleotide phosphorylase, enolase, RhlB (RNA helicase), polynucleotide phosphate kinase, DnaK and GroEL. [RNA degradosomes in vivo: PNAS (2001) 98 63–68.] (See also PROTEASOME.) degranulation (immunol.) See MAST CELL. degron Any feature of a protein which acts as a signal for that protein’s in vivo degradation. One example is the identity of the protein’s N-terminal amino acid residue: see N-END RULE. dehiscence Opening on maturity. dehydration (1) (of specimens) The replacement of water, in a specimen, by a non-aqueous medium, e.g. ethanol. (See also ELECTRON MICROSCOPY; CRITICAL POINT DRYING.) (2) (of foods) See FOOD PRESERVATION (c). (3) (of microorganisms) See DESICCATION. dehydroemetine See EMETINE. dehydrogenase An OXIDOREDUCTASE which catalyses the removal of hydrogen atom(s) from a substrate – the hydrogen being donated to an acceptor other than molecular oxygen; hydrogen acceptors include pyridine nucleotides and flavin nucleotides. (cf. OXIDASE.) Deinococcus A genus of GRAM TYPE-negative (GRAM REACTIONpositive) bacteria. D. radiodurans (formerly Micrococcus radiodurans) is highly resistant to IONIZING RADIATIONS; the cells are red-pigmented cocci in which the outer layers of the cell wall (external to the peptidoglycan) include an OUTER MEMBRANE and

an S LAYER. Carbohydrate chains originating at the outer membrane pass through the S layer and form the outermost surface of the cell. The S layer – also called the HPI (= hexagonally packed intermediate) layer – is composed of a single polypeptide species. [Three-dimensional structure of the HPI layer: JMB (1986) 187 241–253.] D. radiodurans does not contain phosphatidylglycerol or phospholipids derived from it. [Polar lipid profiles of Deinococcus: IJSB (1986) 36 202–206.] The genome is toroidal [Science (2003) 299 254–256]. Dekkera A genus of yeasts (family SACCHAROMYCETACEAE) which reproduce by budding; pseudomycelium is usually formed. Asci are evanescent and are formed directly from (diploid) vegetative cells; ascospores are more or less bowlerhat-shaped, 1–4 per ascus. NO3 − may or may not be assimilated. Two species: D. bruxellensis (anamorph: Brettanomyces bruxellensis) and D. intermedia (anamorph: B. intermedius), found in beers, wines etc. (See also BRETTANOMYCES.) [Book ref. 100, pp. 146–150.] delavirdine See ANTIRETROVIRAL AGENTS. delayed enrichment method See AUXOTROPH. delayed hypersensitivity (DH; delayed-type hypersensitivity; cellmediated hypersensitivity; type IV reaction) (immunol.) In a PRIMED individual: a HYPERSENSITIVITY (sense 1) response which (i) follows the second (or subsequent) exposure to the given antigen, (ii) is mediated by antigen-specific T LYMPHOCYTES, and (iii) involves a local inflammatory reaction that reaches maximum intensity ∼24–48 hours after antigenic challenge. (cf. IMMEDIATE HYPERSENSITIVITY.) Priming and subsequent antigenic challenge may occur in the skin or elsewhere. Initial priming (or ‘sensitization’), in which the individual is initially exposed to the given antigen, involves interaction between an ANTIGEN-PRESENTING CELL (e.g. a DENDRITIC CELL) and an antigen-specific CD4+ T cell. The T cell forms a Th1 clone: when activated by antigen it proliferates and secretes CYTOKINES that include INTERLEUKIN-2. Hence, a primed individual contains an expanded clone of specifically reactive T cells (referred to as TDH , TDTH or Tdth). Sensitization may require a period of ∼1–2 weeks. Following sensitization, a DH reaction can be elicited by further exposure to specific antigen; as before, antigen is presented by an APC, but in this instance the (primed) individual contains an expanded clone of specifically reactive T cells. The secreted cytokines include e.g. interleukin-2, INTERLEUKIN-12 and IFN-g (see INTERFERONS); the cytokines (i) promote expansion of the Th1 subset of T cells (which secrete more pro-inflammatory cytokines) and (ii) bring about the accumulation of activated MACROPHAGES at the site of antigenic challenge. In the skin, the result is typically an indurated (hard), erythematous (red) nodule which develops in 24–48 hours of antigenic challenge. The lesion commonly resolves slowly. However, when there is a failure to eliminate the antigen (or pathogen) the ongoing presence of a concentration of activated macrophages can result in damage to the host’s tissues. In some diseases aggregations of macrophages give rise to epithelioid cells and, subsequently, GIANT CELLS within lesions called GRANULOMAS; tubercles are granulomas formed in tuberculosis. DH to a given antigen can be transferred to a non-primed subject only by the transfer of cells, not serum or plasma alone. (cf. JONES–MOTE SENSITIVITY.) DH reactions can be modified by various drugs; for example, glucocorticosteroids can inhibit DH reactions, and certain antitumour agents, such as mitomycin C, have been found to stimulate DH reactions in mice. 224

dendritic cells DH reactions form the basis of certain diagnostic SKIN TESTS. Thus, an individual suffering from a given microbial disease may be primed in respect of certain antigens of the pathogen; hence, if the patient is given a cutaneous injection of specific antigen, the primed state may be revealed by a DH inflammatory response (a positive skin test) at the site of the injection. (cf. ANERGY.) (See also CONTACT SENSITIVITY.) delayed-type hypersensitivity Syn. DELAYED HYPERSENSITIVITY. deletion mutation A type of MUTATION in which one or more nucleotides are lost from the genome; if the number of nucleotides lost is not divisible by 3, the mutation will be a FRAMESHIFT MUTATION. (cf. INSERTION MUTATION.) Deleya A genus which accommodates the marine species Alcaligenes aestus, A. pacificus, A. cupidus and A. venustus, and Pseudomonas marina [IJSB (1983) 33 793–802]; another species, D. halophila, was isolated from hypersaline soils [IJSB (1984) 34 287–292]. Delhi boil See CUTANEOUS LEISHMANIASIS. 1 (delta plasmid; also: delta transfer factor) An IncIa, low-COPYNUMBER enterobacterial CONJUGATIVE PLASMID. [Structure of the delta plasmid: JGM (1986) 132 3261–3268.] delta agent Syn. DELTA VIRUS. d antigen HDAg: see DELTA VIRUS. delta chain (immunol.) See HEAVY CHAIN. d-endotoxin A glycoprotein entomotoxin produced by Bacillus thuringiensis. Synthesis of the toxin is typically associated with sporulation, the toxin appearing as a (commonly bipyramidal) crystal, the parasporal crystal, near the spore within a sporulating cell; in B. thuringienis subsp. yunnanensis crystals are apparently produced only in asporogenous cells [J. Inv. Path. (1986) 48 254–256]. (Genes concerned with toxin synthesis are apparently plasmid-borne.) The crystal is composed of subunits of a protoxin, the subunits generally being linked by disulphide bonds (which can be disrupted by reducing conditions or by alkaline pH). When crystals and spores are ingested by an insect larva, the crystals dissolve in the alkaline contents of the insect’s midgut to release the protoxin subunits; the subunits are converted by midgut proteases to one or more toxic components which cause paralysis of the gut and degeneration of the midgut epithelium. This may kill the insect directly, or may allow B. thuringiensis to invade the insect and cause a lethal septicaemia. Larvae may be killed within hours of ingesting the toxin. Different strains of B. thuringiensis are effective against different host ranges: those of ‘Group A’ – e.g. B. thuringiensis subsp. kurstaki – are pathogenic primarily in lepidopteran larvae (caterpillars of butterflies and moths), while those in ‘Group B’ – subsp. israelensis – are pathogenic e.g. in mosquito larvae (Diptera); subsp. tenebrionis is pathogenic in some coleopteran (beetle) larvae [d-endotoxin in subsp. tenebrionis: FEMS (1986) 33 261–265]. Strains of B. thuringiensis have been used, worldwide, as ‘microbial insecticides’ for the BIOLOGICAL CONTROL of various lepidopteran pests. Preparations containing spores and crystals (prepared by deep-tank culture of B. thuringiensis) are applied e.g. to crops; repeated applications are necessary because, e.g., both spores and (to a lesser extent) crystals tend to be inactivated by the ultraviolet component of sunlight. (To avoid the need for repeated applications, B. thuringiensis has been genetically modified so that toxin accumulates within the toxin-producing cells; the partly protected (intracellular) toxin is still highly active [Biotechnology (1995) 13 67–71].) Plodia interpunctella, an important lepidopteran pest of stored grain, has been reported

to develop stable and heritable resistance to B. thuringiensis crystals within a few generations [Science (1985) 229 193–195]. (cf. THURINGIENSIN.) [Reviews: Book ref. 171, pp. 185–209 (commercial aspects), pp. 211–249 (genetics of B. thuringiensis); MR (1986) 50 1–24.] (cf. MILKY DISEASE.) d-factor See RNA POLYMERASE. delta hepatitis virus See DELTA VIRUS. delta herpesvirus A herpesvirus which is antigenically related to human varicella-zoster virus (see ALPHAHERPESVIRINAE) and which causes a varicella-like disease in non-human primates. delta particles See TECTIBACTER. delta plasmid See DELTA. d sequence See TY ELEMENT. delta transfer factor See DELTA. delta virus (delta agent; hepatitis D virus; hepatitis delta virus) A defective RNA virus which can replicate only in the presence of a helper virus of the HEPADNAVIRIDAE – usually HEPATITIS B VIRUS (HBV), although under experimental conditions the delta virus can replicate in woodchucks infected with WOODCHUCK HEPATITIS VIRUS. The delta virus virion (as derived from the serum of an HBV-infected patient) is ca. 35–37 nm in diam.; it consists of a core containing the delta virus RNA genome (MWt ca. 5.5 × 105 ) and a delta virus-encoded protein antigen (HDAg) surrounded by an (HBV-encoded) HBsAg-containing envelope. The genome is circular ssRNA [PNAS (1986) 83 8774–8778]. [Protein composition of the delta virus virion: JV (1986) 58 945–950.] In humans, the delta virus can infect an individual either simultaneously with HBV or subsequent to the establishment of an HBV infection; delta virus infection may itself be acute or chronic. The presence of the delta virus may exacerbate the symptoms of HBV infection, in some cases inducing an acute, severe or fulminant hepatitis – particularly when an acute delta virus infection is superimposed on a pre-existing chronic HBV infection. HDAg can be detected in the serum of the patient only very early in infection, but anti-HDAg antibodies apparently persist indefinitely in chronically infected patients; evidence of active delta virus replication requires immunohistological staining for HDAg in the hepatocytes. 1GATP See CHEMIOSMOSIS. 1Gp See CHEMIOSMOSIS. ˜ H+ See CHEMIOSMOSIS. 1m 1p See CHEMIOSMOSIS. 1pH See CHEMIOSMOSIS. 1y See CHEMIOSMOSIS dematiaceous (mycol.) Darkly pigmented. demeclocycline See TETRACYCLINES. demecolcine Deacetyl-N-methyl-COLCHICINE. Demerec convention A widely-followed convention for bacterial genetic nomenclature [Genetics (1966) 54 61–76]. demethylchlortetracycline See TETRACYCLINES. demicyclic rusts Those rust fungi (see UREDINIOMYCETES) which form all types of spore except uredospores; they include e.g. most species of Gymnosporangium. demyelination (demyelinization) The removal or destruction of the myelin sheath of one or more nerve fibres. (See also MULTIPLE SCLEROSIS; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; VISNA.) denaturing gradient gel electrophoresis See DGGE. Dendriscocaulon See CEPHALODIUM. dendritic cells Motile, non-phagocytic ADHERENT CELLS, derived from the bone marrow, which are present e.g. in spleen and 225

dendrodochiotoxicosis lymph nodes. Dendritic cells are irregularly shaped, smoothsurfaced cells which contain pulsatile nuclei and many spherical mitochondria; they bear class II MHC antigens (cf. LANGERHANS’ CELLS) and can act as ANTIGEN-PRESENTING CELLS (see e.g. DELAYED HYPERSENSITIVITY) and as accessory cells for cytotoxic T cells. [Minireviews: Cell (2001) 106 255–274.] dendrodochiotoxicosis (myrotheciotoxicosis) A MYCOTOXICOSIS, affecting domestic animals and man, caused by roridin and verrucarin TRICHOTHECENES produced by Myrothecium spp. Dendrophoma See SPHAEROPSIDALES. Dendrosoma See SUCTORIA. dengue (breakbone fever) An acute, tropical and subtropical human disease caused by any of four serotypes of dengue virus (family FLAVIVIRIDAE) and transmitted by mosquitoes (usually Aedes aegypti ). (The genetic diversity of dengue virus is reported to be increasing, and strains of the virus may now, or in the future, exhibit differences in virulence [TIM (2000) 8 74–77].) Replication of the virus may occur chiefly in macrophages. In most cases the disease is benign and self-limiting (dengue fever ). After an incubation period of ∼5–10 days, typical symptoms include fever, headache, joint and muscular pains, and (often) a rash; bleeding (e.g. haematuria or gingival bleeding) is present in some cases. Mortality rates for this ‘classical’ form of the disease are very low. Less often, a more severe form of disease may develop: dengue haemorrhagic fever (DHF). The manifestations of DHF include high fever, haemorrhagic phenomena, hepatomegaly and thrombocytopenia. The severity of disease is influenced by the extent of plasma leakage (as indicated by the rise in haematocrit reading). The most severe forms of DHF (World Health Organization grades III and IV) are designated dengue shock syndrome (DSS). DSS develops suddenly, after several days’ fever, with signs of circulatory failure/hypovolaemic shock (rapid, weak pulse, narrowed pulse pressure or hypotension, and cold clammy skin); death may occur in 12–24 hours without suitable treatment, but recovery may be rapid following volumereplacement therapy. [Dengue haemorrhagic fever (review): RMM (1995) 6 39–48.] In common with many other diseases caused by arthropodborne viruses, various manifestations of dengue infection (including those in which there is little or no haemorrhage) are characterized by a transient leukopenia [dengue-induced suppression of bone marrow: BCH (1995) 8 249–270]. [Haematology of dengue fever and dengue haemorrhagic fever: BCH (2000) 13 261–276.] Detection of dengue virus in samples of serum can be achieved by rtPCR; in primary infection, detection of viral RNA seems to be optimal prior to seroconversion (soon after onset of symptoms) [JCM (1999) 37 2543–2547]. denitrification Energy-yielding (respiratory) metabolism in which nitrate or nitrite (as terminal electron acceptor) is sequentially reduced to gaseous products, mainly dinitrogen and/or nitrous oxide (cf. DISSIMILATORY NITRATE REDUCTION). It is generally stated that denitrification occurs only under anaerobic or microaerobic conditions; however, aerobic denitrification has been reported [AvL (1984) 50 525–544; denitrification in Rhizobium: SBB (1985) 17 1–9]. In some DENITRIFYING BACTERIA (e.g. Paracoccus denitrificans) electrons from e.g. NADH are transferred to NO3 − via a btype cytochrome, and to NO2 − and N2 O via c-type cytochromes; electron flow to NO3 − , NO2 − and N2 O apparently generates proton motive force. Nitrate reductase is a MOLYBDOENZYME; in some species cytochrome d1 c acts as a nitrite reductase.

(See also NITROGEN CYCLE). denitrifying bacteria Those bacteria capable of DENITRIFICATION; they occur e.g. in soil and in marine and freshwater environments. (Some species can be useful in the elimination of nitrate from waste water.) Examples include e.g. Bacillus licheniformis, Hyphomicrobium sp, Paracoccus denitrificans, Pseudomonas stutzeri and Thiobacillus denitrificans. density gradient centrifugation See CENTRIFUGATION. densonucleosis viruses See DENSOVIRUS. Densovirus (insect parvovirus group; also: densonucleosis viruses, DNVs) A genus of autonomous (helper-independent) viruses (family PARVOVIRIDAE) which infect insects of the Lepidoptera (and probably of the Diptera and Orthoptera). Both positive- and negative-strand ssDNA molecules are encapsidated (in separate virions). Replication occurs in most tissues of host larvae, nymphs and adults; hypertrophy of the nucleus occurs in infected cells, and virions accumulate in dense intranuclear inclusions. Infected insects may die. Type species: densovirus of Galleria mellonella (the greater wax moth, whose larvae – known as waxworms – feed on pollen and wax in beehives). Other members include densovirus of Junonia (a genus of butterflies); similar viruses have been detected in e.g. Aedes (mosquitoes), Bombyx (silk-moth), and butterflies of the Nymphalidae. dental caries Tooth decay: typically, a process in which acids (particularly lactic acid), formed by plaque microorganisms, cause localized breakdown (demineralization) of tooth enamel, thus exposing the dentine; an important factor in the development of caries is the formation of water-insoluble extracellular microbial glucans which promote adhesion of cariogenic bacteria to the tooth surfaces (see DENTAL PLAQUE). Various bacteria, including e.g. lactobacilli and Streptococcus mutans, can be cariogenic in man; the development of carries may depend on factors such as the nature of the plaque microflora, diet, and the level of immunity in the host (see also CREVICULAR FLUID). Fluoride is a potent anti-caries agent. It converts the apatite in tooth enamel to the more stable (acid-resistant) fluorapatite, and this is believed to be the primary mode of fluoride anticaries activity. Fluoride can also inhibit bacterial metabolism e.g. by blocking the uptake of sugars by the PEP-dependent phosphotransferase system (see FLUORIDES). However, in some oral streptococci (including S. mutans) there is an alternative, fluoride-insensitive, pmf-dependent uptake system for glucose; this is a low-affinity uptake system compared to the high-affinity PTS system (the latter operating as a scavenger system under conditions of substrate limitation). At low pH (e.g. 5.5) the fluoride-insensitive system appears to be more important than the PTS system for the uptake of glucose. dental plaque On the surfaces of teeth: a thin film (up to ca. 0.5 mm thick) consisting of a mixed microbial flora embedded in a matrix composed largely of extracellular (capsular) bacterial polysaccharides and salivary polymers; it is a predisposing factor in DENTAL CARIES and PERIODONTITIS. Early colonizers of a clean enamel surface (in man) include species of Neisseria and Streptococcus (particularly S. sanguis). If plaque is allowed to build up, the nature of the microflora changes with time; although streptococci tend to remain dominant, anaerobes and filamentous bacteria begin to appear in significant numbers after several days or a week. Organisms present in well-established plaque include e.g. species of ACTINOMYCES (particularly A. viscosus), BACTEROIDES and VEILLONELLA; there is a general correlation between the numbers of Streptococcus mutans (see STREPTOCOCCUS) and the dietary intake of sucrose. The nature of the plaque microflora varies e.g. from one individual to another, and from one site to another on a given tooth. 226

Dermatocarpon Bacterial polymers typically present in plaque include MUTAN and LEVANS. The presence of plaque can be detected by rinsing the mouth with a solution of a dye (‘disclosing agent’) such as erythrosin. Dentalina See FORAMINIFERIDA. deodorants (skin) See SKIN MICROFLORA. 5′ -deoxyadenosylcobalamin See VITAMIN B12 . deoxycholate A salt of deoxycholic acid (see BILE ACIDS). deoxycholate–citrate agar See DCA. deoxycholic acid See BILE ACIDS. deoxycoformycin Syn. pentostatin (see VIDARABINE). 2′ -deoxy-2′ -fluoro-5-methyl-1-b-D-arabinosyluracil See FMAU. deoxyhemigossypol A terpenoid PHYTOALEXIN produced by the cotton plant. [Role of terpenoid phytoalexins in the resistance of a cultivar of Gossypium barbadense to Verticillium dahliaeinduced wilt: PPP (1985) 26 209–218.] deoxynivalenol See TRICHOTHECENES. deoxyribonuclease (DNase; DNAase) An enzyme which depolymerizes DNA. A DNase is designated DNase I (EC 3.1.21.1) or DNase II (EC 3.1.22.1) according to whether the mono- or oligonucleotide products of its action have (terminal) 5′ - or 3′ phosphate groups, respectively. DNases are produced e.g. by the pancreas and by many microorganisms. In staphylococci, production of a thermostable, Ca2+ requiring, extracellular DNase (‘thermonuclease’: a 5′ phosphodiesterase with both endo- and exonuclease activity, yielding 3′ -nucleotides) correlates closely with the production of COAGULASE; thermonuclease also has Ca2+ -dependent RNase activity. (Many coagulase-negative staphylococci produce a DNase which is generally heat-labile.) DNase activity may be detected/assayed e.g. by measuring changes in turbidity, or increasing levels of acid-soluble nucleotides (measured by spectrophotometry at 260 nm), induced in a suspension of DNA. For the detection of DNase production on solid media, an agar medium (e.g. trypticase–soy agar) containing DNA and a calcium salt is inoculated with the test strain and incubated for 18–24 hours. The plate is then flooded with 1 N HCl to precipitate DNA. A clear zone (in which the DNA has been hydrolysed) surrounds each DNase-producing colony. Certain dyes – e.g. methyl green (which combines only with highly polymerized DNA) – may be used instead of HCl, in which case cell viability may be preserved. [Book ref. 44, pp. 757–768.] Certain Clostridium spp produce DNases: e.g. the b-toxins of C. chauvoei and C. septicum. See also STREPTODORNASE. deoxyribonucleic acid See DNA. deoxyribonucleoside See NUCLEOSIDE. deoxyribophage A BACTERIOPHAGE with a DNA genome. deoxyribovirus A VIRUS with a DNA genome. 2-deoxystreptamine 2-Deoxy-1,3-diaminoinositol, a component of many AMINOGLYCOSIDE ANTIBIOTICS. DEPC DIETHYLPYROCARBONATE. Dependovirus (adeno-associated viruses, AAVs; adeno-satellite viruses) A genus of defective viruses (family PARVOVIRIDAE) which are totally dependent on functions of a co-infecting helper adenovirus (or herpesvirus) for their replication. Dependoviruses can infect a wide range of vertebrate hosts. Type species: AAV-1 (AAV type 1), which infects mainly monkeys; other members: AAV-2 and AAV-3 (which can infect man), AAV-4 (common e.g. in African green monkeys), avian AAV, bovine AAV and canine AAV. (Equine AAV and ovine AAV are probable members of the genus.) In vitro, a given AAV seems able to replicate in any type of cell culture which can support the replication of a suitable helper virus.

Genome: linear ssDNA, 4675 bases long in AAV-2 [sequence in AAV-2: JV (1983) 45 555–564]. Both positive and negative strands are encapsidated (in separate virions). The DNA has terminal INVERTED REPEATS 145 bases long. Within each repeat, the first 125 bases include a PALINDROMIC SEQUENCE in which bases 1–41 are complementary to bases 125–85; between bases 41 and 85 are two shorter palindromic sequences (bases 42–62 and 64–84). Folding which permits maximum base-pairing thus results in a T-shaped structure. (cf. PARVOVIRUS.) Initial stages of AAV infection are independent of helper virus; the virions adsorb to a host cell and subsequently enter the nucleus, where the DNA is uncoated. In the presence of a coinfecting helper virus, the DNA is replicated and transcribed, its mRNA is translated, and infectious virions are formed. DNA replication appears to be initiated at the hairpin structures and is independent of RNA primers. In the absence of a helper virus, the AAV establishes a latent state by integrating into the host DNA as a provirus. Subsequent infection of the latently infected cell by a helper virus ‘rescues’ the AAV DNA, allowing the formation of infectious AAV virions. AAVs appear not to cause disease in their hosts. In vitro, they may have a strong inhibitory effect on the replication of their helper viruses, but in vivo they seem not to ameliorate symptoms of adenovirus infection to any significant extent (although AAVs have been shown to reduce the oncogenic potential of adenoviruses in hamsters and of herpes simplex virus in cell cultures). AAV-2 infecting cell cultures co-infected with human cytomegalovirus (HCMV) as helper apparently exacerbates HCMV-induced CPE [Virol. (1985) 147 217–222]. [Reviews in Book ref. 97.] depside An ester formed by the condensation of two or more phenolcarboxylic acids; e.g., COOH.ArO.CO.ArOH is a generalized didepside where Ar = a phenolic group. Depsides occur e.g. as ‘lichen substances’ (see LICHEN) and as components of TANNINS (e.g. digallic acid). depsipeptide antibiotics ANTIBIOTICS which are derivatives of depsipeptides (molecules containing both ester and peptide bonds). They include the cyclic octadepsipeptide intercalating agents (QUINOXALINE ANTIBIOTICS) and the cyclic depsipeptide ionophores (see e.g. ENNIATINS and VALINOMYCIN). (See also DIDEMNINS.) Derbesia A genus of siphonaceous, tropical or temperate, epilithic or epiphytic green seaweeds (division CHLOROPHYTA) which exhibit a heteromorphic alternation of generations. The sporophyte and gametophyte are so distinct morphologically that they have been described as separate plants: e.g. Halicystis, with a bulbous vesicular thallus, is the gametophyte of a filamentous Derbesia sporophyte; some species of Bryopsis have also been shown to have Derbesia sporophyte stages. Derbesia sporophytes produce stephanokont zoospores, while gametophytes produce biflagellate anisogametes. (See also CELL WALL.) derepressed (mol. biol.) Refers to the state of a repressible gene or operon when it is not repressed, i.e., when the gene or operon is expressed. Derepression may be brought about e.g. by the presence of a specific inducer: see OPERON. (See also DRD PLASMID.) dermatitis Inflammation of the skin. It is commonly due to mechanical or chemical irritants or to allergic reactions, but may occur in certain infectious diseases (e.g. RINGWORM.) (cf. ECZEMA.) dermatitis verrucosa Syn. CHROMOBLASTOMYCOSIS. Dermatocarpon A genus of foliose LICHENS (order VERRUCARIALES); photobiont: a green alga. Thallus: small, more or less 227

dermatomycosis lobed, attached to the substratum (rocks) by a central holdfast (umbilicus – cf. UMBILICARIA). Pseudothecia occur immersed in the thallus, their ostioles visible as black dots in the thallus surface. Some species – e.g. D. rivulorum, D. weberi (formerly D. fluviatile) – occur on rocks in or adjacent to unpolluted streams or lakes. (cf. CATAPYRENIUM.) dermatomycosis Any MYCOSIS affecting the skin – see e.g. CANDIDIASIS, PITYRIASIS VERSICOLOR, RINGWORM. dermatophilosis A disease of animals, transmissible (by direct contact) to man, caused by Dermatophilus congolensis (see e.g. LUMPY WOOL and STRAWBERRY FOOT-ROT). In man, self-limited pustular lesions develop on the skin. (cf. PITTED KERATOLYSIS.) Dermatophilus A genus of aerobic or facultatively anaerobic, catalase-positive bacteria (order ACTINOMYCETALES, wall type III) which occur as pathogens of man and other animals (see DERMATOPHILOSIS). In culture the organisms initially form filaments (ca. 6.0) than normal meat; during stress, muscle glycogen in the living animal is converted to lactic acid (cf. MEAT SPOILAGE) which is subsequently lost when the animal is bled. DFD meat is more susceptible than normal meat to spoilage. Increased susceptibility to aerobic spoilage appears to be due to the deficiency of glucose rather than to the high pH; since little or no glucose is available, spoilage organisms attack amino acids earlier than in normal meat and, hence, produce off-odours and off-flavours after a shorter period of storage [Book ref. 30, pp. 240–244]. Anaerobic spoilage (e.g. in vacuum packs) may be due to organisms (e.g. Alteromonas putrefaciens, Serratia liquefaciens) which are inhibited by the low pH of normal meat. S. liquefaciens produces off-odours. A. putrefaciens forms H2 S which reacts with e.g. myoglobin to produce a green compound: sulphmyoglobin (‘greening’) – cf. MEAT SPOILAGE (b); since A putrefaciens is inhibited at pH below 6.0, greening can be prevented by treating the meat with citrate buffer. Vacuum-packed DFD meat may also support the growth of large populations of Yersinia enterocolitica, although these seem not to cause significant spoilage (cf. FOOD POISONING). DFMO (DL-a-difluoromethylornithine) See SLEEPING SICKNESS. DFP Diisopropylfluorophosphate – see PROTEASES. DGGE Denaturing gradient gel electrophoresis: a method for comparing samples of related double-stranded DNA (generated e.g. by PCR or restriction) by two-dimensional electrophoresis (cf. SSCP). In DGGE [Biotechnology (1995) 13 137–139], fragments are separated by size in the first phase of electrophoresis. Then, in the same gel, the fragments are moved electrophoretically at right-angles to their original path. In this second phase,

the organisms contain c-type cytochromes; elemental sulphur, which acts as terminal electron acceptor, is reduced to H2 S (dissimilatory sulphur reduction), and acetate (or other substrate) is completely oxidized to CO2 . (See also ANAEROBIC DIGESTION.) (Sulphate, sulphite or thiosulphate cannot be used as terminal electron acceptor.) Fumarate or L-malate can be fermented to acetate and succinate. Optimum growth temperature: 30° C. Optimum pH: 7.2–7.5. Colonies are pink or peach-coloured, translucent to opaque. GC%: ca. 50–63. Type species: D. acetoxidans. Strains which are ovoid, with a polar or subpolar flagellum, and which do not use alcohols as substrates have been referred to as ‘D. acetexigens’. [Book ref. 22, pp. 664–666.] determinant (1) (antigenic determinant; determinant group; epitope) (immunol.) Of an antigenic macromolecule: any region of the macromolecule with the ability or potential to elicit, and combine with, specific antibody. Determinants exposed on the surface of the macromolecule are likely to be immunodominant, i.e. more immunogenic than other (immunorecessive) determinants which are less exposed, while some (e.g. those within the molecule) are non-immunogenic (immunosilent ). (See also ANTIGEN.) (2) (genetics) A gene or functional gene group. detritivore Any organism (e.g. earthworm, lugworm, bivalve mollusc) which feeds by ingesting detritus (such as soil particles), removing and digesting e.g. adherent microorganisms, and voiding the residue. Detroit-6 An ESTABLISHED CELL LINE derived from human sternal bone marrow; the cells are heteroploid and epithelioid. Dettol See PHENOLS. Dettol chelate A disinfectant which contains chloroxylenol (see PHENOLS) and EDTA; EDTA potentiates the action of chloroxylenol on Gram-negative bacteria by increasing cell permeability. It is active against e.g. many strains of Pseudomonas aeruginosa. deuteromycetes See DEUTEROMYCOTINA. Deuteromycotina (deuteromycetes; Fungi Imperfecti) A nonphylogenetic category originally created for fungi with no known sexual stage; the category still includes fungi with no known sexual stage (and some fungi which form neither conidia nor sexual structures: see AGONOMYCETALES), but it also includes the asexual (= anamorphic, conidial or imperfect) stages of various fungi which are now known to have a sexual (= teleomorphic or perfect) stage in the Ascomycotina or the Basidiomycotina. For convenience, ‘Deuteromycotina’ is generally treated as a subdivision within the EUMYCOTA. The conidium-forming deuteromycetes are arranged into form genera (see FORM GENUS) primarily on the basis of the characteristics of their conidia and their modes of conidiogenesis (see CONIDIUM). (See also SACCARDOAN SYSTEM.) The inclusion of a number of form species in a given form genus means only that those fungi have similar asexual stages; such fungi are not necessarily related (and are often unrelated) in an evolutionary sense (as determined by the sexual characteristics of the organisms, when known). Thus, a given form genus may contain e.g. anamorphs corresponding to the teleomorphs of different genera together with ANAHOLOMORPHS. (For convenience, the word ‘form’ is generally omitted when referring to a form genus, form species etc.) Classification of the deuteromycetes on the basis of their asexual stages facilitates the identification of those members in which the asexual stage is that which is most commonly encountered in nature (and which may form the sexual stage only rarely). Two classes [Book ref. 64, p. 112]: COELOMYCETES and HYPHOMYCETES. 231

DHBG fragments move through an increasing concentration of DNAdenaturing agents (e.g. formamide + urea) so that, at certain levels in the gradient, localized sequence-dependent melting (i.e. strand separation) occurs within part(s) of the fragments (base-pairing being stronger in GC-rich sections); such localized melting affects the electrophoretic speed of those fragments in which it occurs and allows separation of fragments in the gel. [Example of use of DGGE (differentiation of isolates of Escherichia coli by analysis of the 16S–23S intergenic spacer region): FEMS Ecol. (2001) 35 313–321.] Other uses of DGGE include e.g. characterization of organisms by comparing PCR-amplified sequences of their 16S rRNA genes [AEM (1996) 62 340–346] and detection of Rhizobium spp [LAM (1999) 28 137–141]. Another method, based on the same principle, replaces the chemical denaturing gradient of DGGE with an ongoing increase in temperature during the second phase of electrophoresis; thus, at certain levels of temperature, localized sequence-dependent melting occurs in specific part(s) of the fragments – affecting electrophoretic mobility and allowing separation within the gel. This method is referred to as temporal temperature gradient gel electrophoresis (TTGE). [Comparison of DGGE with TTGE: LAM (2000) 30 427– 431.] DHBG (9-(3,4-dihydroxybutyl)-guanine) An ANTIVIRAL AGENT which is active, both in cell cultures and in vivo, against herpes simplex viruses (HSV-1 and -2); the (R)-enantiomer is more effective than the (S )-enantiomer. The mechanism of action resembles that of ACYCLOVIR, but DHBG has higher affinity for HSV thymidine kinase. DHBV DUCK HEPATITIS B VIRUS. Dhori virus An unclassified virus (see ORTHOMYXOVIRIDAE) which has been isolated from ticks; antibodies to the virus have been found in man and domestic animals. DHPA ((S )-DHPA; (S )-9-(2,3-dihydroxypropyl)-adenine) An ANTIVIRAL AGENT which acts as an analogue of adenosine; it is a potent inhibitor of 5-adenosyl homocysteine hydrolase. DHPA is active e.g. against vaccinia, herpes simplex, varicella-zoster and measles viruses; it acts synergistically with VIDARABINE. (The (R)-enantiomer is inactive.) DHPG (9-(1,3-dihydroxy-2-propoxymethyl)-guanine; 2′ -nor-2′ -deoxyguanosine, 2′ -NDG) An ANTIVIRAL AGENT which has potent activity against herpes simplex viruses (HSV-1 and -2); it is not effective against e.g. Epstein–Barr virus, varicella-zoster virus or cytomegaloviruses. The mechanism of action resembles that of ACYCLOVIR. The isomer (S )-9-(2,3-dihydroxy-1-propoxymethyl)guanine is also active against HSV-1 and -2. DI particle DEFECTIVE INTERFERING PARTICLE. diacetoxyscirpenol See TRICHOTHECENES. diacetyl (dimethylglyoxal; CH3 .CO.CO.CH3 ) A water-soluble compound formed e.g. by certain lactic acid bacteria; it may also be derived by oxidation of acetoin in the BUTANEDIOL FERMENTATION. (See also VOGES–PROSKAUER TEST.) Diacetyl produced by certain lactic acid bacteria is responsible for the characteristic ‘buttery’ flavour and aroma in many fermented DAIRY PRODUCTS. The diacetyl is formed from pyruvate – see Appendix III(c) – but levels of diacetyl are low if the pyruvate is derived from hexoses only. Additional pyruvate (and hence diacetyl) can be produced from citrate by certain strains of lactic acid bacteria (‘aroma bacteria’, ‘flavour bacteria’) – e.g. Lactococcus lactis and Leuconostoc cremoris (see LACTIC ACID STARTERS). (Citrate is naturally present in cows’ milk at levels of ca. 0.2%, with seasonal fluctuations; it may also be added to

the milk to enhance diacetyl production.) L. lactis produces both lactic acid and diacetyl in milk. However, Leuconostoc cremoris by itself grows poorly in milk, producing little lactic acid; it can take up citrate only at pH below ca. 6.0, so that diacetyl production by this organism requires the activities of a lactic acid producer such as L. lactis. The ability to produce diacetyl from citrate is apparently plasmid-linked in at least certain strains of L. (‘Streptococcus’ ) lactis [AvL (1983) 49 265–266]. The ratio of flavourful products (e.g. diacetyl) to flavourless products (e.g. acetoin) depends e.g. on the redox potential of the system. Diacetyl has some antimicrobial activity [AEM (1982) 44 525–532], being more effective against Gram-negative bacteria, yeasts and moulds than against Gram-positive bacteria. diacridine A compound containing two ACRIDINE moieties (linked e.g. by a hydrocarbon bridge); it may act as a bis INTERCALATING AGENT. diagnosis (1) In NOMENCLATURE: a list of descriptive characteristics which distinguish a proposed new taxon from other taxa. (2) (med.) In general, a statement of the identity of a given disease, deduced from symptoms etc., or the procedure used for arriving at such a statement. diagnostic window See TRANSFUSION-TRANSMITTED INFECTION. diakinesis See MEIOSIS. Dialister pneumosintes See BACTEROIDES (B. pneumosintes). dialkylnitrosamines See N-NITROSO COMPOUNDS. diamidines Compounds with two amidine [NH2 .C(=NH)−] groups. Aromatic diamidines bind to DNA, and a number of them are trypanocidal agents which bind to kinetoplast DNA and cause structural changes in the kinetoplast; however, there is evidence that at least part of the trypanocidal effect in vivo is due to inhibition of ornithine decarboxylase, leading to depletion of putrescine. (See e.g. BERENIL; DAPI; 2-HYDROXYSTILBAMIDINE; PENTAMIDINE ISETHIONATE.) diaminopimelic acid pathway (DAP pathway) A pathway for lysine biosynthesis [Appendix IV(e)] which occurs in bacteria, certain lower fungi (Hyphochytriales, Leptomitales, Saprolegniales) and e.g. in green plants. (cf. AMINOADIPIC ACID PATHWAY.) diaminopyrimidine drugs See FOLIC ACID ANTAGONIST. diamond skin disease Syn. SWINE ERYSIPELAS. dianemycin See MACROTETRALIDES. o-dianisidine (fast blue B) A (carcinogenic) substance, 3,3′ -dimethoxybenzidine, used e.g. in assays for HYDROGEN PEROXIDE: the peroxidase-dependent oxidation of o-dianisidine causes increased absorbance at 500 nm. dianthoviruses (carnation ringspot virus group) A category of PLANT VIRUSES which have a wide host range and are transmitted mechanically and via the soil. Virion: icosahedral, ca. 31–34 nm diam., containing two molecules of positive-sense ssRNA (MWts ca. 1.5 and 0.5 × 106 ) and one type of coat protein (MWt 40000). Virus replication appears to occur in the cytoplasm. Type member: carnation ringspot virus; other members: red clover necrotic mosaic virus, sweet clover necrotic mosaic virus. diapedesis See INFLAMMATION. diaphorase Any enzyme which can catalyse the oxidation of reduced NAD or NADP by an artificial electron acceptor. diaphoromixis Bipolar or tetrapolar multi allele HETEROTHALLISM. diaplectic metachrony See METACHRONAL WAVES. Diaporthales An order of fungi (subdivision ASCOMYCOTINA) which include saprotrophic and plant-parasitic species. Ascocarp: perithecioid, often immersed; hamathecium: absent or evanescent. Asci: unitunicate, evanescent. Genera: e.g. Diaporthe, ENDOTHIA, GAEUMANNOMYCES, Gnomonia (see also ZYTHIA). 232

diatoms etc which are usually arranged in symmetrical, species-specific patterns. The degree of cell wall silicification may vary to some extent with environmental conditions, and exceptionally the wall may be predominantly or entirely organic (e.g. in Phaeodactylum tricornutum – see PHAEODACTYLUM – and in Cylindrotheca fusiformis). [Details of wall structure: Book ref. 137, pp. 129–156.] Two main groups of diatoms are commonly recognized: centric diatoms, in which the valve is radially symmetrical, and pennate diatoms, in which the valve is bilaterally symmetrical. (Some diatoms do not fit easily into either category: e.g. Triceratium spp may have 3-, 4- or 5-fold rotational symmetry; see also HEMIDISCUS.) Centric diatoms are mostly marine and planktonic, are nonmotile, and commonly exhibit oogamous sexual reproduction in which the male gametes each bear a single tinsel flagellum. Genera include e.g. Arachnoidiscus, Bacteriastrum, Biddulphia, CHAETOCEROS, Coscinodiscus, Cyclotella, Hemiaulus, MELOSIRA, Skeletonema, Stephanodiscus, Stephanopyxis, Thalassiosira, Zygoceros. Pennate diatoms occur in various habitats; many are capable of gliding motility, and many exhibit isogamous sexual reproduction involving cell–cell contact (conjugation). All species which are capable of GLIDING MOTILITY (q.v.) have a raphe: basically, a slit which (usually) runs the length of the valve, interrupted by a central nodule. Such ‘raphid’ species are generally benthic or occur attached to a solid substratum. In a few genera (e.g. Achnanthes, Cocconeis) a raphe occurs in only one of the two valves, but in most a raphe occurs in both valves. Pennate diatoms which lack a raphe (‘araphid’ diatoms: e.g. Fragilaria, Striatella, Tabellaria) cannot glide; these organisms may have a central line, ridge, or unornamented central area called a pseudoraphe. (Other pennate diatoms include e.g. AMPHORA, Anomoeoneis, Bacillaria, Cylindrotheca, Cymbella, Diatoma, GOMPHONEMA, Gyrosigma, NAVICULA, Nitzschia, PHAEODACTYLUM, Pinnularia, Pleurosigma, Stauroneis, Surirella.) In many centric and pennate diatoms the cells adhere to one another to form filaments or characteristic groupings (see e.g. ASTERIONELLA and MELOSIRA); the cells may be held together by mucilage secreted via tubular projections in the frustule and/or by the interlocking of spines present on the margins of the valves. Secreted mucilage may also serve to attach some forms to the substratum, and apparently serves an essential role in GLIDING MOTILITY. Asexual reproduction occurs by binary fission. The nucleus (which is diploid in vegetative cells) moves from its position near the epivalve to the cell centre, and the protoplast expands, pushing the two valves apart. New girdle bands are formed, and mitosis occurs. The original parent hypovalve becomes the epivalve of one daughter cell, and both daughter cells synthesize a new hypovalve. Thus, the epivalve is always the older of the two valves in a cell, and – in species in which the epivalve is larger than the hypovalve – one of the daughter cells must be smaller than the parent cell. When division is complete, the nucleus in each cell returns to its position near the epivalve face. The new siliceous structures (valves and cingulum) are synthesized in SILICA DEPOSITION VESICLES beneath the plasmalemma, reaching the exterior by fusion between the silicalemma and plasmalemma. [Diatom wall formation: Book ref. 137, pp. 157–200; silicon ‘biomineral’ synthesis in diatoms: TIBS (1987) 12 151–154.] Since, in many species, the average size of cells in a population progressively decreases with increasing numbers of

Diaporthe See DIAPORTHALES. diarrhoea (American: diarrhea) Frequent passage of fluid stools: a symptom of many types of illness. (cf. DYSENTERY; see also SCOURS.) Diarrhoea may be due to e.g. (i) the effect on the gut mucosa of particular microbial toxins which cause hypersecretion of fluid into the lumen; (ii) failure of the gut to absorb small molecules (peptides, sugars – especially lactose) due e.g. to damage to, or non-functioning of, the mucosa, leading to an osmotic effect in the gut lumen; (iii) abnormal activity of the smooth musculature of the gut wall. Severe diarrhoea may lead to dehydration and loss of electrolyte; treatment includes rehydration with solutions containing Na+ , Cl− , Ca2+ , bicarbonate ions and glucose. Some causes of persistent diarrhoea include e.g. CLB and EAGGEC. (See also CRYPTOSPORIDIOSIS and ETEC.) Diaspora See EIMERIORINA. diaspore Syn. PROPAGULE. diastase Syn. AMYLASE. diastatic Able to metabolize starch. diastole See CONTRACTILE VACUOLE. Diatoma See DIATOMS. diatomaceous earth (diatomite; kieselguhr) A siliceous material composed largely of fossil diatom frustules (see DIATOMS), large natural deposits of which are mined in various parts of the world (particularly Lompoc, California). Diatomaceous earth is used e.g. as a mild abrasive (in toothpastes, polishes etc), as an absorbent, as a heat-insulating material, and in various types of filter (including certain microbiological filters: see FILTRATION). diatomite Syn. DIATOMACEOUS EARTH. diatoms A large group (>10000 species) of ALGAE (often regarded as a distinct division – Bacillariophyta) which are essentially unicellular (some are colonial, some form filaments) and which have a characteristic type of CELL WALL consisting typically of a siliceous structure (the frustule) encased in an organic layer. Most cells have brownish chloroplasts containing chlorophylls a, c1 and c2 and e.g. fucoxanthin; storage products include CHRYSOLAMINARIN. Many species are facultatively heterotrophic in the dark; a few marine benthic species are obligately heterotrophic. Diatoms are unusual, if not unique, in having an absolute requirement for silicon – not only for the construction of their walls but also for general metabolism (e.g. in Cylindrotheca fusiformis silicon affects gene expression both directly and indirectly [JGM (1985) 131 1735–1744]). Species occur in aquatic environments, including fresh, brackish and marine waters (where they may be benthic, planktonic, epiphytic etc. – see also AUFWUCHS), and in terrestrial environments such as soil, damp rocks, and even dry rocks and desert sands. Achnanthes exigua is a thermophile (optimum temperature for photosynthesis: 42° C) found in hot springs. Psychrophilic species form a major component of the ‘ice algae’ present on the lower surfaces of ice in polar seas [JGM (1983) 129 1019–1023]. Diatoms occur as endosymbionts e.g. in members of the FORAMINIFERIDA. (See also RHIZOSOLENIA and RHOPALODIA.) The diatom frustule consists of two valves – which, according to species, may each be saucer-shaped, bowl-shaped, boat-shaped etc. – held together by two or more siliceous bands (girdle bands) which, collectively, form the cingulum. In many species one valve (the epivalve or epitheca) is slightly larger than the other (hypovalve or hypotheca); the cingulum, which is attached to the edges of the valves, may overlap the hypovalve to a greater or lesser extent. The valves are characteristically elaborately ornamented with pores, slits, ribs, tubes, projections, 233

diatoxanthin Dick test A SKIN TEST used to determine whether or not an individual is susceptible to SCARLET FEVER. The test procedure (similar to that used in the SCHICK TEST) involves an intradermal injection of the erythrogenic toxin of Streptococcus pyogenes. A positive Dick test (indicating susceptibility) consists of an inflammatory response (at the site of the injection) which becomes evident within ca. 12 hours and reaches peak intensity within ca. 24 hours of the injection. In immune individuals the toxin is neutralized by antitoxin, thus giving a negative test. dicloran An agricultural antifungal agent (2,6-dichloro-4nitroaniline) which is used against various Botrytis infections. It is water-insoluble – hence very persistent – and is usually formulated as a dust; it has very low phytotoxicity. (cf. CHLORONITROBENZENES.) dicloxacillin See PENICILLINS. Dictyocha See SILICOFLAGELLATES. Dictyoglomus A genus of bacteria. One species: D. thermophilum, an anaerobic, caldoactive, asporogenous chemoorganotroph; cells: rod-shaped, occurring in large spherical bodies consisting of a few to many separate cells. [IJSB (1985) 35 253–259.] Dictyosiphon See PHAEOPHYTA. dictyosome (1) One of the stacks of membranous vesicles which form a GOLGI APPARATUS. (2) Syn. Golgi apparatus. dictyosporae See SACCARDOAN SYSTEM. Dictyostelia See EUMYCETOZOEA. dictyostelids See DICTYOSTELIOMYCETES. Dictyosteliia See EUMYCETOZOEA. Dictyosteliomycetes (dictyostelid cellular slime moulds; dictyostelids) A class of cellular SLIME MOULDS (division MYXOMYCOTA). (cf. EUMYCETOZOEA.) The organisms occur mainly in soil, humus and dung, particularly in tropical regions. The vegetative phase consists of myxamoebae which form filose subpseudopodia; flagellated cells are not formed. The life cycle involves a feeding stage, during which myxamoebae ingest food (mainly bacteria) and divide mitotically. When the food supply is exhausted, the amoebae stop growing and, after a period of starvation (pre-aggregation phase or ‘interphase’), the aggregation phase begins: numerous myxamoebae converge (chemotactically – see ACRASIN) and join together to form one to many multicellular, macroscopic pseudoplasmodia. In most species, the pseudoplasmodium can migrate over the surface of the substratum and can show tactic responses. Eventually, the pseudoplasmodium stops moving and differentiates to form a multicellular, multispored, stalked fruiting body, the sorocarp (a process known as culmination); the sorocarp stalk consists of a cellulosic ‘stalk tube’ which, when mature, is either hollow or filled with dead cells. The spores are dispersed by wind, rain, etc; on germination, each spore releases a myxamoeba, thus initiating a new cycle. (In some species myxamoebae may not always pass through this life cycle, forming instead MICROCYSTS and/or MACROCYSTS.) Genera: e.g. ACYTOSTELIUM, DICTYOSTELIUM, POLYSPHONDYLIUM. [Dictyostelids – natural history, life cycles, cultivation: Book ref. 144.] Dictyostelium A genus of slime moulds (class DICTYOSTELIOMYCETES) in which the sorocarp stalk tube is filled with a mesh of empty cell walls (cf. ACYTOSTELIUM) and bears a spherical sorus of spores at its apex. In e.g. D. discoideum the sorocarp consists of a single unbranched stalk that tapers from base to tip; the proximal end is flared into a basal attachment disc, and the distal end bears a single, more or less spherical, white to yellowish mass (sorus) of ellipsoidal to reniform spores (each typically ca. 2.5–3.5 × 6.0–9.0 µm). In some species the sorocarp may

divisions, maximum cell size must eventually be re-established; this may be achieved by the formation of resting spores or auxospores. Resting spores generally have thick ornamented walls; on germination, the protoplast expands to maximum cell size prior to wall formation. Auxospores are usually or always formed as a result of fusion of gametes, after which the zygote protoplast escapes from the parent wall, expands, and then synthesizes a wall which is initially organic; a siliceous wall is then synthesized. (See also DIATOMACEOUS EARTH.) diatoxanthin See CAROTENOIDS. diatretyne nitrile See POLYACETYLENES. Diatrypales See ASCOMYCOTINA. diauxie The phenomenon in which, when provided with two sources of carbon, an organism preferentially metabolizes one source (completely) before starting to metabolize the other; the two phases of growth are commonly separated by a lag phase in which the organism produces enzyme(s) necessary for the utilization of the second source of carbon. (See also CATABOLITE REPRESSION.) diauxy Syn. DIAUXIE. diazaborines A range of antibacterial agents [JB (1989) 171 6555–6565] which apparently inhibit fatty acid biosynthesis by inhibiting the enzyme enoyl-acyl carrier protein reductase (ENR). diazomycin A See DON. 6-diazo-5-oxo-L-norleucine See DON. diazotroph Any organism capable of NITROGEN FIXATION. dibromoaplysiatoxin See LYNGBYA. dibromomethylisopropyl-p-benzoquinone An inhibitor of PHOTOSYNTHESIS. dibromopropamidine An aromatic diamidine used as an antiseptic; it is active mainly against asporogenous Gram-positive bacteria. DIC DISSEMINATED INTRAVASCULAR COAGULATION. dicarboximides A group of agricultural ANTIFUNGAL AGENTS which are effective against Botrytis cinerea; they are used on a wide range of crops, functioning primarily as surface protectants. Dicarboximides include e.g. iprodione and vinclozolin. Dice–Leraas diagrams Diagrams that are used for identifying and describing trypanosomes on the basis of their measurements (e.g. length, distances between organelles). Dicellomyces See BRACHYBASIDIALES. dicentric (of a eukaryotic chromosome) Having two CENTROMERES. dichlofluanid A sulphur-containing ANTIFUNGAL AGENT used e.g. for the control of Botrytis cinerea in plants, and in antifungal washes for the prevention of mould in buildings. dichlone (2,3-dichloro-1,4-naphthoquinone) A QUINONE ANTIFUNGAL AGENT used as a seed dressing (e.g., for the seeds of legumes or cotton) and as a foliar spray; it is effective against a range of diseases, including apple scab, damping off, etc. Dichlone is toxic to certain plants, and is also effective in controlling BLOOMS of certain cyanobacteria. dichloramine T See CHLORINE. dichloroisocyanurate (DCCA) (as an antimicrobial agent) Sodium or potassium dichloroisocyanurate, available in powder or tablet form, hydrolyses in water to form hypochlorous acid (see HYPOCHLORITES). When dry, DCCA salts are stable at room temperature. dichlorophane (dichlorophene) See BISPHENOLS. 3-(3,4-dichlorophenyl)-1,1-dimethylurea See DCMU. Dichothrix See RIVULARIACEAE. 234

Didinium be sparingly and irregularly branched (cf. POLYSPHONDYLIUM); in D. polycephalum several sorocarps occur in a coremium-like cluster in which the stalks are fused over much of their length, becoming free at their distal, spore-bearing ends. Sorocarps of Dictyostelium spp vary in size from e.g. ca. 0.2–0.6 mm in D. deminutivum to 30 mm or more in D. giganteum; those of D. discoideum may reach a maximum height of ca. 4.0–4.5 mm, but are usually smaller. [Species descriptions and key: Book ref. 144, pp. 246–367.] During the feeding stage of the life cycle, Dictyostelium myxamoebae feed mainly on bacteria, but sometimes ingest other myxamoebae of the same species (‘cannibalism’); D. caveatum is unusual in that it feeds extensively on the myxamoebae of other slime moulds as well as on bacteria. [Self/non-self recognition in D. caveatum: JCB (1986) 102 298–305.] D. discoideum is the best-known species, being widely used in studies on differentiation and cell-cell interactions. It is easily cultured in the laboratory (e.g. on hay infusion agar or SM MEDIUM, with Escherichia coli or Klebsiella pneumoniae as food); some strains can be grown in cell-free media. (The main natural habitat of D. discoideum is apparently deciduous forest soils and leaf-litter.) The vegetative amoebae are commonly ca. 13–16 × 9–11 µm; they are haploid and uninucleate, and contain one or more contractile vacuoles, food vacuoles, etc. They are attracted to their prey by CHEMOTAXIS, chemoattractants apparently including e.g. folic acid released by the bacteria. When food is exhausted, cells enter the pre-aggregation phase (see DICTYOSTELIOMYCETES) during which the myxamoebae discharge their food vacuoles, become smaller, show altered staining properties, and lose the ability to respond chemotactically to folic acid but acquire the ability to be attracted by cyclic AMP (cAMP). Each cell contains six chromosomes, the largest being chromosome 2 (about 25% of the genome). [Sequence and analysis of chromosome 2: Nature (2002) 418 79–85.] In D. discoideum the aggregation phase begins when a subset of myxamoebae begins to secrete cAMP (an ACRASIN) in slow, rhythmic pulses. The cAMP diffuses out from these cells and binds to cell-surface cAMP receptors on nearby myxamoebae. Binding of cAMP to the receptors triggers several responses in the cell: e.g., it (transiently) stimulates adenylate cyclase activity within the cell, resulting in greatly increased production and release of cAMP from the cell, and it triggers migration of the cell towards the source of the cAMP. Thus, the pulses of cAMP are progressively amplified and relayed from the initial subset of cAMP-producing cells throughout the population, resulting in the formation of converging streams of cells which move in regular steps with intervening ‘rest’ periods. In order to maintain the cAMP gradient and to prevent swamping of the receptors by excess cAMP, the concentration of extracellular cAMP is strictly controlled by regulation of the relative proportions of (at least) two proteins: a cAMP phosphodiesterase (which occurs in both soluble extracellular and membrane-bound forms, and which hydrolyses cAMP), and a glycoprotein phosphodiesterase inhibitor (which binds to and inactivates the soluble – but not the bound – form of the enzyme). The aggregated cells adhere to one another, eventually forming a pseudoplasmodium. The multicellular, elongated pseudoplasmodium (called a ‘slug’ or ‘grex’) consists of a mass of cells enclosed within a slime sheath which is composed of cellulose microfibrils embedded in a protein- and carbohydrate-containing matrix. The slug varies in size (e.g. ca. 0.5–2.0 mm long) depending on the number of cells it contains. It migrates over the surface of the

substratum, exhibiting e.g. aerotaxis, phototaxis and thermotaxis. The slime sheath does not move relative to the substratum, and may provide traction against which the cells within can move; thus, as the slug moves forwards, a slime trail of collapsed sheath material remains behind. New sheath material is synthesized along the length of the slug, so that the sheath is thinnest at the anterior end, becoming progressively thicker towards the posterior. A migrating slug can split into two smaller slugs, or two slugs can merge to form a larger slug; the size (but not the proportions) of the sorocarp which eventually develops depends on the size of the slug at culmination. The fates of the cells during culmination are apparently determined at the slug migration stage (i.e., before culmination begins): the cells making up the anterior third of the slug are prestalk cells, destined to form the sorocarp stalk, while the cells of the posterior two-thirds are prespore cells. [Patterns of cell differentiation within the slug: Book ref. 67, pp. 255–274.] The culmination process begins when the slug stops moving and reorientates such that the leading (anterior) tip is raised vertically above the rest of the cell mass, forming a nipple-like apical projection. A short cellulosic ‘stalk tube initial’ is secreted by cells near the apex; the entire cell mass then flattens, bringing the tube down through the cell mass to the substratum. Prestalk cells within the lower end of the tube enlarge, become vacuolated and compacted, and eventually die; the stalk lengthens upwards – the remaining prestalk cells progressively undergoing vacuolation and death to result eventually in the characteristic mesh of cellulose cell walls which fills the cellulose stalk tube. Meanwhile, the mass of prespore cells is gradually elevated on the growing stalk, becoming progressively differentiated into spores from the periphery to the centre of the mass. Differentiation is complete when all the cells have become either stalk cells or spores. The sorocarp is usually orientated such that the sorus is at the maximum distance from the substratum or from adjacent objects (including other sorocarps); this orientation is believed to be due to a tropism regulated by an (unidentified) gas or vapour produced by the developing sorocarp. The spores have thick cellulosic walls and are resistant to e.g. desiccation. Germination generally occurs only in the presence of an adequate supply of amino acids. Spores in masses fail to germinate owing to the presence of an autoinhibitor apparently produced during culmination. In D. discoideum macrocysts may be formed, but microcysts have not been observed. Dictyota See PHAEOPHYTA. Dictyuchus See SAPROLEGNIALES. dicyandiamide (DCD; Didin) Cyanoguanidine, a NITRIFICATION INHIBITOR. [Mineralization of DCD in acid soils: SBB (1985) 17 253–254.] N,N′ -dicyclohexylcarbodiimide See DCCD. didanosine See NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS. didemnins Cyclic depsipeptide ANTIVIRAL AGENTS isolated from Caribbean tunicates (sea-squirts); they are probably too cytotoxic for therapeutic use. dideoxy fingerprinting See TUBERCULOSIS (antibiotic resistance testing). dideoxy sequencing See DNA SEQUENCING. dideoxyribonucleotide See NUCLEOTIDE (figure legend). dideoxythymidine triphosphate See DDTTP. Didesmis See GYMNOSTOMATIA. Didin See DICYANDIAMIDE. Didinium A genus of freshwater ciliates (subclass GYMNOSTOMATIA). Cells: radially symmetrical, ovoid or barrel-shaped, ca. 235

Didymella site, the 3′ -AAA . . . tail on polyadenylated mRNA molecules. The task is made manageable by converting only some of the (many) mRNAs from each population; selectivity is achieved with a primer such as 5′ -TT . . . TTGG-3′ which permits conversion of only those mRNAs in which a cytosine (C) residue occurs in the appropriate position after the 3′ -AAA . . . tail. cDNAs from each of the populations are then fingerprinted by subjecting them to ARBITRARILY PRIMED PCR and separating the products by gel electrophoresis. When fingerprints from different populations are compared, any band(s) of interest – such as band(s) present in one fingerprint but not in other(s) – can be further examined by removal from the gel and amplification by the same arbitrary primer; the amplified fragments may be e.g. sequenced and/or used to probe a library. [Differential display methodology: NAR (1998) 26 5537– 5543; review: Biotechniques (2002) 33 338–346.] differential host (plant pathol.) A plant host which, on the basis of disease symptoms, serves to distinguish between various strains or races of a given plant pathogen. differential interference-contrast microscopy See MICROSCOPY (d). differential medium See MEDIUM. diffluent Readily dissolving or breaking up in water. Difflugia A genus of testate amoebae (order ARCELLINIDA) in which the test is reinforced with sand grains, diatom frustules, sponge spicules etc which are initially ingested by the cell. D. urceolata is multinucleate and has a rounded test (ca. 200–230 × 150–200 µm) with a pointed top and a rim around the ventral aperture through which several narrow, round-ended pseudopodia emerge. Difflugia spp occur in ponds, swamps, bogs, soil etc. diffusely adherent E. coli See ENTEROADHERENT E. COLI. diffusion-coupled gradostat See GRADOSTAT. diffusion test (1) In ANTIBIOTIC-sensitivity testing: any test which involves the diffusion of antibiotic(s) through agar. See e.g. DISC DIFFUSION TEST and AGAR DIFFUSION TEST. (2) (for membrane filters) A test used to determine the physical integrity of a membrane filter (see FILTRATION). If a wetted membrane is subjected to a pressure lower than its bubble point pressure (see BUBBLE POINT TEST), some air can pass through the pores by simple diffusion; the amount of air transmitted in this way can be significant in filters of large surface area. In the diffusion test a wetted filter is subjected to pressure at ca. 80% of its bubble point pressure, and the volume of air transmitted is determined; the integrity of the filter is assessed by comparing this volume with that expected from an intact filter. DL-a-difluoromethylornithine See SLEEPING SICKNESS. difolatan Syn. CAPTAFOL. DIG Abbreviation for DIGOXIGENIN. digenetic Refers to a parasite which carries out part of its life cycle in each of two different host species. (cf. HETEROXENOUS.) di George syndrome (congenital thymic aplasia) The condition, resulting from an undeveloped thymus gland, which is characterized by a lack of T LYMPHOCYTES; those with this syndrome are susceptible to a range of infections, especially by intracellular pathogens. The condition has been treated by transplantation of fetal thymus gland (using tissue from a fetus at Lk0 , t is positive. (When Lk = Lk0 , t = 0, and the molecule is relaxed.) In general, naturally occurring supercoiled DNA is negatively supercoiled (cf. REVERSE GYRASE). The superhelical density, s, of a given molecule is the number of superhelical turns per turn of the helix in relaxed DNA, i.e., s = 10.4t/N. The equation t = Lk − Lk0 assumes that the pitch of the double helix, and hence the number of turns in the helix, remains constant (at the value for the relaxed molecule, Lk0 ), so that any supercoils are accommodated entirely by writhe. However, the strain of supercoiling may force a change in pitch, and hence a change in the number of turns in the double helix – the actual number of turns, the twist (Tw ), being related to the pitch (p) of the helix by the expression T w = N/p; by convention, Tw is positive for a right-handed helix. Pitch, and hence twist, can also be altered by the insertion of an INTERCALATING AGENT. Twist differs from the linking number in that, in a given cccDNA molecule, the amount of twist can vary depending on the amount of writhe; the linking number is invariable and is the sum of twist and writhe. Thus, W r = Lk − T w, and, since Lk is constant for a given molecule, any change in writhe must be accompanied by an equal and opposite change in twist, and vice versa; when T w = Lk0 , W r = t, and when W r = 0, T w = Lk. [PNAS (1976) 73 2639–2643.] The positive free energy associated with negative supercoiling has a number of important consequences for the biological behaviour of DNA. It facilitates the formation of certain secondary structures (e.g. HAIRPINS, CRUCIFORMS, localized regions 243

DNA cloning isolates of the human immunodeficiency virus (HIV-1) has been investigated in this way with the object of linking particular mutations with resistance to protease inhibitors [Nature Medicine (1996) 2 753–759]. Chip technology can also be used for examining the differential expression of genes: with an array of immobilized, singlestranded cDNAs (which bind mRNAs of expressed genes), fluorophore-labelled probes (with binding sites elsewhere on the mRNA molecules) can be used to detect those genes which are active under specific conditions. Chips can be made by (i) immobilizing pre-existing molecules, or (ii) ‘on-chip synthesis’ – in which high-speed robotic devices can synthesize a vast range of nucleotide combinations on a single chip. One problem with microarrays is that (single-stranded) DNA probes have a tendency for intra-strand base-pairing – which may obscure target sequences. A possible solution may be the use of microarrays containing PNA probes because PNA–DNA hybridization can occur in the absence of salts (that is, under conditions which inhibit intra-strand base-pairing in ssDNA). Among the growing number of published uses, high-density arrays have been used to identify species of Mycobacterium and (simultaneously) to test for resistance to rifampicin [JCM (1999) 37 49–55]. The need to include a sufficiently comprehensive range of probes for a given investigation has been demonstrated in another study in which non-clade-B strains of HIV-1 were examined for resistance to antiretroviral agents using an assay system designed for clade B isolates of HIV-1; the assay was unsatisfactory for non-clade-B isolates – indicating the need to ensure that future assays can accomodate newly emergent strains of HIV-1 [JCM (1999) 37 2533–2537]. [DNA chips (reviews): Nature Biotech. (1998) 16 27–31 & 40–44; TIBtech. (1999) 17 127–134. Biomedical discovery with DNA arrays (review): Cell (2000) 102 9–15.] DNA cloning See CLONING. DNA delay mutant A mutant of BACTERIOPHAGE T4 which, on infection of a host cell, shows delayed synthesis of T4 DNA (particularly in Escherichia coli B strains) and a reduced burst size. The mutation occurs in genes 39, 52 or 60 – genes encoding subunits of the T4 TOPOISOMERASE; a DNA delay mutant requires a functional host GYRASE for replication, the gyrase presumably replacing T4 topoisomerase in an essential function in the initiation of early DNA replication. DNA-dependent RNA polymerase See RNA POLYMERASE. DNA–DNA hybridization See DNA HOMOLOGY. DNA fingerprinting (chromosomal fingerprinting; also: restriction enzyme analysis, restriction endonuclease analysis, REA) A method used for TYPING. Essentially, chromosomal DNA, isolated from a culture of the given strain, is first cleaved by a RESTRICTION ENDONUCLEASE; the fragments (of many different lengths) are then separated by gel electrophoresis into a series of bands – which are stained. The pattern of bands, reflecting the cutting sites of the given RE in the chromosome, is the fingerprint of the strain. Strains which differ e.g. through loss or gain of a restriction site (perhaps through a point mutation) will give different fingerprints; similarly, insertion or deletion mutations (or e.g. insertion/excision of phage DNA) will alter the length of particular fragments and will also give rise to changes in the fingerprint. Hence, strains can be typed on the basis of their fingerprints. One problem with this method is that it may yield too many fragments – giving a complex fingerprint which is difficult to

interpret. One solution to the problem is to use a ‘rare-cutting’ RE (see table in RESTRICTION ENDONUCLEASE); this gives fewer, larger fragments that can be analysed e.g. by PFGE. Alternatively, the original procedure can be carried out with additional use of a labelled probe that reveals only those (few) fragments to which the probe binds; an example of this approach is RIBOTYPING (q.v.). [Evidence from DNA fingerprinting of endoscopic crossinfection in post-endoscopic acute gastritis (Helicobacter pylori ): JCM (2000) 38 2381–2382.] (See also FINGERPRINTING.) dna genes In Escherichia coli : those genes whose products are involved in at least some types of DNA REPLICATION. See separate entries for genes dnaA, dnaB, dnaC (= dnaD), nrdA (= dnaF), dnaI, dnaJ, dnaK, dnaP and dnaT. For dnaE, dnaN, dnaQ, dnaX and dnaZ (= dnaH) see DNA POLYMERASE. For dnaG see PRIMASE. For dnaW see adk gene. DNA glycosylase See ADAPTIVE RESPONSE and URACIL-DNA GLYCOSYLASE. DNA gyrase Syn. GYRASE. DNA helicases Syn. HELICASES. DNA homology The degree of similarity (‘relatedness’) between base sequences in different DNA molecules (or in different parts of the same DNA molecule); two DNA molecules which are 100% homologous have identical sequences of nucleotides. In microbial TAXONOMY the degree of homology between samples of chromosomal DNA from different organisms can be used to indicate the taxonomic relationship of the organisms. The homology between two samples of dsDNA can be assessed by various indirect methods (as well as by sequencing each sample and making a direct comparison of the nucleotides); two approaches are outlined below. In DNA–DNA hybridization, single-stranded (heat-denatured) chromosomal DNA from one test strain (strain A) is bound to a membrane (e.g. nitrocellulose). Chromosomal DNA from another test strain (strain B) is fragmented (for example, by ULTRASONICATION) and the fragments denatured by heat to singlestranded pieces. Similar, single-stranded fragments are also made from labelled DNA of strain A. Under appropriate conditions, the unlabelled, single-stranded DNA from strain A (which is bound to the membrane) is then exposed to the singlestranded fragments from strains A and B; the concentration of B fragments is very much higher than that of the A fragments. This allows the fragments to hybridize, by base-pairing, with complementary sequences in the bound DNA. The fragments from strains A and B compete for sequences on the bound DNA. However, the concentration of B fragments is very much higher than that of A fragments; consequently, if strains A and B are very similar, few (if any) of the (labelled ) A fragments will hybridize. On the other hand, if strains A and B are very different many of the A fragments will hybridize. Thus, the similarity between strains A and B is indicated by the number of A fragments which hybridize; this can be determined by measuring the label on the A fragments after all unbound fragments have been washed away. Such an assay requires controls; in one control, the assay is carried out with only labelled A fragments – this indicating the maximum amount of binding by A fragments. Results are meaningful only if the A fragments hybridize stably; the stability of binding can be assessed by monitoring the dissociation of A fragments from the bound DNA as the temperature is gradually raised. Homology may also be assessed by comparing the thermal stability of HETERODUPLEXes formed from two samples of DNA 244

DNA polymerase with the thermal stability of the corresponding homoduplexes. This involves determining the mid-point temperature [Tm ] of the thermal melting curve of both the homoduplexes and heteroduplexes (see THERMAL MELTING PROFILE). The homology of DNAs from strains A and B are then assessed by comparing the Tm of the A homoduplexes with that of A–B heteroduplexes – the difference between the two values of Tm [= 1Tm ] indicating the degree of base pair mis-matching in the heteroduplex. [Methods for determining the homology of nucleic acids: Book ref. 138, pp 33–74.] DNA ligase A LIGASE which can make a phosphodiester bond between the 3′ -OH end of one ssDNA strand and the (physically juxtaposed) 5′ -phosphate end of the same or another ssDNA strand; thus, e.g., a DNA ligase can repair a NICK in one strand of a dsDNA molecule, the ends being held in position by basepairing with the intact strand. (See also e.g. DNA REPLICATION.) DNA looping (transcriptional control) See OPERATOR. DNA methylation Methylation of certain bases in DNA: a normal process which occurs in many or most organisms. In prokaryotes, methylation typically occurs at the N-6 position of adenine and/or at the C-5 position of cytosine, while in most eukaryotes methylation occurs mainly at the C-5 position of cytosine; the bases which are methylated generally occur in a specific sequence of nucleotides – e.g. the second cytosine residue in the sequence CC(A/T)GG is methylated in Escherichia coli strain C. (See also DAM GENE and FROG VIRUS 3.) Methylation serves various functions: see e.g. RESTRICTION–MODIFICATION SYSTEM. It also promotes a certain type of SPONTANEOUS MUTATION. (See also MISMATCH REPAIR.) [DNA methylation: molecular biology and biological significance: Book ref. 222.] DNA modification A physiological process in which bases in DNA are substituted with methyl or other groups – commonly shortly after synthesis of the DNA (see e.g. DNA METHYLATION; cf. BACTERIOPHAGE MU and BACTERIOPHAGE T4). Modification may occur as part of a RESTRICTION–MODIFICATION SYSTEM or may be involved e.g. in the regulation of gene expression (cf. DAM GENE). DNA photolyase See PHOTOREACTIVATION. DNA polymerase A type of enzyme which forms a polymer of deoxyriboNUCLEOTIDES by condensing deoxyribonucleoside triphosphates (dNTPs) with the elimination of pyrophosphate. A DNA polymerase adds nucleotides to the 3′ -OH end of a preexisting strand of DNA or an RNA primer; the order in which the nucleotides are added is dictated by the nucleotide sequence of a template strand of DNA (see DNA REPLICATION) or, in some cases, RNA (see REVERSE TRANSCRIPTASE). DNA polymerases function processively (see PROCESSIVE ENZYME). Prokaryotic DNA polymerases. The bacterium Escherichia coli encodes three main DNA polymerases which are designated I, II and III (see also DNA POLYMERASE IV and DNA POLYMERASE V). All three main polymerases have exonuclease activity as well as polymerase activity; all can remove nucleotides sequentially from the 3′ end of a strand, and polymerases I and III can also cleave nucleotides from the 5′ end. (See also KLENOW FRAGMENT.) The 3′ -to-5′ exonuclease activity of a DNA polymerase is required for proof-reading during DNA REPLICATION. Polymerase I (Kornberg enzyme, product of gene polA) is active in DNA repair (see EXCISION REPAIR); it is also involved in the removal of RNA primers during DNA replication, and is needed for the replication of certain plasmids (e.g. ColE1). Polymerase I can act as an RNA-dependent DNA polymerase (i.e. a reverse transcriptase) but it exhibits poor processivity in

this capacity and requires longer incubation times compared with a reverse transcriptase [EMBO (1993) 12 387–396]. Polymerase II (polB product) is induced in the SOS SYSTEM (q.v.). Polymerase III is the main replicative enzyme in E. coli and is responsible for replication of the chromosome and of phage DNA etc. ‘DNA polymerase III’ refers to a core enzyme consisting of three different subunits: (i) subunit a (product of dnaE /polC ), which is involved in polymerization; (ii) subunit e (product of dnaQ/mutD), which has 3′ -to-5′ exonuclease activity and is apparently involved in proof-reading [PNAS (1983) 80 7085–7089] (see also MUTATOR GENE); and (iii) q (of unknown function). The core enzyme of polymerase III can catalyse limited DNA synthesis on single-stranded gaps in dsDNA, but for full efficiency, accuracy and processivity on longer templates it requires a number of additional subunits which include: (i) the b subunit (dnaN product; ?‘Factor I’), which apparently contributes to processivity; (ii) the g subunit (dnaZ product), which apparently also contributes to processivity; (iii) the d subunit (dnaX product; ?‘Factor III’), which apparently enhances processivity; and (iv) the t subunit (product of the dnaX-Z region), which acts as a link between two core enzymes. The core enzyme together with the full range of subunits is called DNA polymerase III holoenzyme. (DNA polymerase III∗ refers to the holoenzyme minus the b subunit. DNA polymerase III′ refers to a complex of core enzyme plus the t subunit.) In a current model of DNA replication, the holoenzyme functions as a dimer – the enzymes being physically linked via their t subunits; during replication, one enzyme forms the leading strand while the other forms the lagging strand, i.e. they work in opposite directions. In other bacteria, DNA polymerases appear to be essentially similar to those in E. coli. In the Archaea, DNA polymerases may be significantly different (see e.g. APHIDICOLIN). In some prokaryotes (those that inhabit high-temperature environments), the DNA polymerases are thermostable, and this feature is exploited in various techniques used for the amplification of nucleic acids in vitro (e.g. PCR); these enzymes include: (a) Taq DNA polymerase. An enzyme (from the bacterium Thermus aquaticus) which has been widely used in PCR (particularly during the early years); this enzyme lacks 3′ -to5′ exonuclease activity and (therefore) has no proof-reading capacity. (b) Stoffel fragment. A modified, recombinant form of the Taq polymerase (the C-terminal region of the protein) which is more thermostable than the parent enzyme; it lacks 5′ -to-3′ (in addition to 3′ -to-5′ ) exonuclease activity. This enzyme is active in a wide range of concentrations of magnesium ions, and has been found useful e.g. in those forms of PCR which use arbitrary primers. (c) UlTma DNA polymerase (Perkin-Elmer). This recombinant form of the DNA polymerase of Thermotoga maritima has 3′ -to-5′ exonuclease activity and can repair 3′ mismatches during PCR – such proof-reading ability making the enzyme useful for high-fidelity copying. (d) Pfu DNA polymerase (Stratagene). This highly thermostable enzyme from Pyrococcus furiosus retains 95% activity after 1 hour at 98° C; it has excellent proof-reading ability. Eukaryotic DNA polymerases. Eukaryotes also have a number of DNA polymerases, including (in most eukaryotic cells) polymerases a, b and g. Each type of polymerase appears to 245

DNA polymerase I be associated with a particular function – for example, the g polymerase carries out DNA replication in mitochondria. Some viruses (e.g. bacteriophage T4) encode their own DNA polymerases; others (e.g. phages fd, fX174, G4) use host enzymes. DNA polymerase I (Kornberg enzyme) In Escherichia coli : an enzyme associated e.g. with EXCISION REPAIR and with the removal of RNA primers during DNA replication. (See also DNA POLYMERASE.) DNA polymerase II In Escherichia coli : a polymerase induced in the SOS SYSTEM. (See also DNA POLYMERASE.) DNA polymerase III In Escherichia coli : the major DNA polymerase; it is involved in chromosomal replication and e.g. synthesis of phage DNA. For further details see entry DNA POLYMERASE. DNA polymerase IV In Escherichia coli : the product of gene dinB (induced in the SOS SYSTEM), a protein which has DNA polymerase activity and which appears to be involved in mutagenesis; DinB has no proof-reading activity. DNA polymerase V In Escherichia coli : a protein complex, consisting of two UmuD′ proteins and one UmuC protein, which has DNA polymerase activity and which may carry out some instances of DNA repair (translesion synthesis) during induction of the SOS SYSTEM. DNA polymorphism See POLYMORPHISM (sense 3). DNA primase Syn. PRIMASE. DNA repair Any physiological process in which damaged DNA within a cell is recognized and repaired; damage in this context generally means any alteration or distortion of the normal double-helical structure of dsDNA resulting e.g. from the presence of abnormal bases or base pairs, nicks or gaps in one strand, covalent linkages between bases etc. (but not from replacement of one normal base pair with another: cf. MUTATION). Repair may involve e.g. direct reversal of the damage (e.g. Ada protein in ADAPTIVE RESPONSE) or removal of the damaged region followed by its replacement with normal DNA (e.g. EXCISION REPAIR). Repair systems may be constitutive or inducible. See e.g. ADAPTIVE RESPONSE, BASE EXCISION REPAIR, EXCISION REPAIR, MISMATCH REPAIR, PHOTOREACTIVATION, RECOMBINATION REPAIR and SOS SYSTEM. DNA replication The process in which a copy (i.e. a replica) of a double-stranded DNA molecule is synthesized. In vivo, circular, dsDNA molecules may be replicated by the CAIRNS’ MECHANISMS or the ROLLING CIRCLE MECHANISM; the following refers mainly to the replication of circular dsDNA molecules by the Cairns’ mechanism (replication of linear dsDNA is also considered briefly). (For replication of DNA in vitro see e.g. PCR and SDA.) During replication, a new strand of DNA is synthesized on each of the two pre-existing strands, each pre-existing strand being used as a pattern or template; a template dictates the sequence of nucleotides in a new strand, thus conserving the genetic information encoded in the template strand. Essentially, molecules of deoxyribonucleoside triphosphate (dNTPs) basepair with complementary nucleotides in each template strand and are sequentially polymerized (with elimination of pyrophosphate) by a DNA POLYMERASE. Note that each newly synthesized strand is complementary to – not a copy of – the template strand on which it is synthesized; thus, each of the two new daughter duplexes produced from a given parent duplex consists of one parent strand and one newly synthesized strand. (This type of replication is called semiconservative replication because only one strand in each daughter duplex has been newly synthesized.)

Initiation of DNA replication occurs at one or more special sites, called origins (designated ori ); any DNA molecule which lacks an origin cannot be replicated in vivo. (See also REPLICON.) Initiation of replication involves the recognition of an ori site by various initiation factors and enzymes. An essential prerequisite for replication is separation of the two strands of dsDNA (so-called ‘melting’) in the ori region (see CELL CYCLE (b)). As no known DNA polymerase can initiate synthesis of a new strand of DNA on a template, initiation of DNA replication (by the Cairns’ mechanism) requires the provision of a ‘starter’ sequence of nucleotides (a primer ) which the DNA polymerase can elongate (in the 5′ -to-3′ direction) to form a new strand of DNA; DNA synthesis is usually primed by a short strand of RNA which is transcribed on the DNA template strand in the ori region. Chain elongation (i.e. ongoing strand synthesis) involves ongoing separation (unwinding) of the two strands of the parental duplex. Termination of DNA synthesis usually occurs when the entire duplex has been replicated (cf. ROLLING CIRCLE MECHANISM); it involves dissocation of the replicating machinery, joining of the two ends of each daughter strand (in the case of circular dsDNA molecules), and separation of the two circular daughter molecules (decatenation). Newly synthesized strands usually undergo modification before the next round of replication can begin (see RESTRICTION–MODIFICATION SYSTEM). Replication of the chromosome in Escherichia coli. The way in which a round of replication is initiated (i.e. triggered) is not known, but various factors appear to be relevant; regulation of the initiation of DNA replication in E. coli is discussed in the entry CELL CYCLE. Once triggered, replication of the ccc dsDNA CHROMOSOME of E. coli occurs by the Cairns’ mechanism: replication begins at the origin – oriC (see ORIC) – and proceeds bidirectionally, both template strands being replicated more or less simultaneously. Thus, two migrating, Y-shaped replication forks (in which the stem of the Y is the parental duplex, and the arms the daughter duplexes) move in opposite directions around the chromosome (see figure). Because the strands of the parent duplex are antiparallel, and because both new strands are synthesized more or less simultaneously in the direction of movement of a replication fork, one daughter strand is synthesized in the 5′ -to-3′ direction while the other is synthesized from the 3′ direction. The strand synthesized in the 5′ -to-3′ direction (the leading strand – see figure) is synthesized continually, but the other strand (lagging strand) cannot be synthesized continually because no known DNA polymerase can synthesize DNA in the 3′ -to-5′ direction. The lagging strand is actually synthesized as a series of fragments (Okazaki fragments – see figure), each fragment being synthesized in the 5′ -to-3′ direction from a separate RNA primer. Primers are subsequently excised and replaced with DNA (by extension from the preceding fragment) and the ends are joined together by a DNA LIGASE. Chromosomal replication is a complex process requiring a number of different proteins. These proteins include the dnaA gene product (see DNAA GENE); a dimer of DNA polymerase III (see DNA POLYMERASE); GYRASE; topoisomerase I (see TOPOISOMERASE); HU PROTEIN; the DNAB GENE product (a helicase); PRIMASE and RNA POLYMERASE. At least some of these proteins are components of an initiation complex (earlier name: 246

DNA replication

5′

3′

primer 'leading' strand DNA duplex

3′

5′ 3′

2nd primer

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Okazaki fragment 1st primer

5′

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3′ 5′

DNA REPLICATION (Cairns-type): disposition of template and newly synthesized strands at a replication fork (diagrammatic; see entry). In a circular DNA duplex the strands have separated, locally, in the ori region. Only one half of this region is shown; in this half, the strands of the duplex will continue to separate in a left → right direction (i.e. the replication fork is moving to the right). On one template strand (top) an RNA primer (zigzag line) has been synthesized (see text); ongoing addition of deoxyribonucleotides to the 3′ end of this primer will form the ‘leading’ strand of DNA. Synthesis of the leading strand is continuous in the 5′ -to-3′ direction. On the other template strand (below), the 1st primer has been synthesized (by a primase), and this (RNA) primer has been extended as a strand of DNA by sequential addition of deoxyribonucleotides from the 3′ end. This new strand of DNA may form the first Okazaki fragment of the lagging strand; alternatively, it may act as a primer for leading strand synthesis in the other replication fork (not shown). Following synthesis of the 1st primer, the replication fork has moved further to the right – opening up the duplex to the extent shown in the diagram. The 2nd primer has been synthesized and has been extended as a strand of DNA (Okazaki fragment) as far as the 5′ end of the first primer. As the replication fork moves even further to the right additional template will become available, and the 3rd, 4th, 5th . . . etc. primers synthesized on this template will (like the 2nd primer) be extended as Okazaki fragments; the sequence of Okazaki fragments will be joined together (forming the lagging strand) when the (RNA) primers are replaced by DNA. Modified from Bacteria, 5th edition, Figure 7.8(a), page 116, Paul Singleton (1999) copyright John Wiley & Sons Ltd, Chichester, UK (ISBN 0471-98880-4) with permission from the publisher.

In a current model for DNA replication, a processive complex of proteins (‘replisome’) is associated with each replication fork. The complex includes a DNA polymerase III dimer (the two enzymes physically linked via their t subunits and orientated in opposite directions) – one enzyme synthesizing the leading strand while the other synthesizes the lagging strand. The complex also contains a PRIMOSOME which, in turn, includes a helicase and the DnaG protein (a primase); the helicase is described as a hexamer (a ring-shaped structure of six DnaB proteins) which unwinds the duplex [Cell (1996) 86 177–180]. In this model, a section of lagging-strand template (liberated by ongoing leading-strand synthesis) forms a loop at the replication fork. This allows primer synthesis for the lagging strand (by primase) followed by extension of the primer by DNA polymerase III; when a newly synthesized fragment approaches the 5′ -end of the previous fragment, the new (doublestranded) section is released by the complex, and the process is repeated on the next region of exposed lagging-strand template. Thus, the complex synthesizes both leading and lagging strands concurrently as it moves along with the replication fork.

‘orisome’). (During strand synthesis, parts of the parent DNA molecule – around the replication forks – necessarily exist in a single-stranded state, and these ssDNA sequences are stabilized by SINGLE-STRAND BINDING PROTEINS.) A short RNA primer, synthesized on one of the template strands, is elongated by DNA polymerase III in the 5′ -to-3′ direction to form the leading strand (see figure); synthesis of the primer may be mediated by RNA polymerase (RNA polymerase is needed for initiation of DNA replication). Exposure of the other template strand permits synthesis of the lagging strand. Primers for the lagging strand are synthesized by a PRIMASE (dnaG gene product) that forms part of a PRIMOSOME. Each primer is elongated in the 5′ -to-3′ direction to form an Okazaki fragment (∼1000–2000 nt in length) that extends to the 5′ end of the previous primer. (Primers are subsequently removed and replaced by DNA; this involves the enzyme DNA polymerase I.) As the first replication fork moves away, the first fragment of the lagging strand may act as a primer for leading strand synthesis in the opposite direction. At 37° C a replication fork moves at about 1000 nt per second. 247

DNA restriction The physical link between the two enzymes in the DNA polymerase III dimer is apparently needed for co-ordination of synthesis of the leading and lagging strands. It appears that coupling is also needed between the helicase and the polymerases – loss of such coupling being associated with a drastic reduction in efficiency of the helicase [Cell (1996) 84 643–650]. Moving in opposite directions, the two replications forks meet at the ter site on the chromosome, 180° from oriC. During replication, the DNA polymerase appears to recognize only the overall shape of a base-pair, i.e. the same active site of the enzyme must serve for all four possible basepair combinations. The accuracy of DNA synthesis therefore depends initially on base-pairing specificity between incoming nucleotides and template DNA. This might be expected to result in a relatively high frequency of errors because tautomerism in the bases can interfere with the accuracy of base-pairing. However, the overall error rate in E. coli DNA replication has been estimated to be ca. one mistake in 108 –1010 nucleotides polymerized – a much higher level of accuracy than can be accounted for by base-pairing and polymerase specificities. This level of accuracy is achieved by ‘proof-reading’ and ‘editing’ systems which recognize and correct errors in a newly synthesized strand. The 3′ -to-5′ nuclease activity of DNA polymerase III holoenzyme serves a proof-reading function, removing mispaired nucleotides from the growing (3′ ) end of the chain before continuing chain elongation. Errors which escape this system may be detected and corrected subsequently by the post-replicative MISMATCH REPAIR system. In growing cells, chromosomal replication must be coordinated with cell division in order that daughter cells each receive the full genetic complement; the rate of DNA replication in E. coli is increased during faster growth by the initiation of additional rounds of synthesis (see HELMSTETTER–COOPER MODEL). Conditions which inhibit DNA replication may cause inhibition of cell division (see SOS SYSTEM). Replication of linear genomes. In some bacteria a linear chromosome is replicated bidirectionally from an internal origin of replication. This raises the question of how the replication machinery avoids leaving the 3′ end of the template strand (in each daughter duplex) as single-stranded DNA. In one of several models, DNA synthesized on the new strand (at the fully duplexed end) displaces the 5′ terminal nucleotide sequence of the template strand – which is then transferred to (complementary) single-stranded DNA on the other daughter duplex (thus filling the single-stranded gap). [Replication of linear DNA molecules: TIG (1996) 12 192–196.] In some viruses, replication of the linear dsDNA genome involves so-called protein priming – in which a nucleotide, bound covalently to a (virus-encoded) ‘terminal protein’, forms the 5′ terminus of a new strand; this system is found e.g. in BACTERIOPHAGE f29 [protein priming in phage f29: EMBO (1997) 16 2519–2527] and in members of the ADENOVIRIDAE. Chromosomal replication in eukaryotes. Replication of eukaryotic CHROMOSOMES occurs during the S phase of the cell cycle. DNA synthesis is initiated at many separate sites along the chromosome, and replication forks proceed bidirectionally until they meet and fuse. Each DNA molecule is replicated only once in a cell cycle. [Eukaryotic DNA replication (minireview): Cell (1987) 48 7–8.] Plasmid and phage replication. Mechanisms of replication in PLASMIDS and (DNA) phages may differ significantly from chromosome replication in the corresponding host cell, but in

most or all cases at least some of the components involved in host chromosomal replication are required. In plasmid ColE1, replication is of the Cairns’ type – but it occurs unidirectionally from the origin; in the F PLASMID replication is bidirectional (as in the E. coli chromosome). Many of the small circular plasmids in Gram-positive bacteria replicate by means of a ROLLING CIRCLE MECHANISM [replication control in rolling circle plasmids: TIM (1997) 5 440–446]. Plasmid replication, and the partitioning to daughter cells, seems likely to involve some kind of association between the plasmid and the cytoplasmic membrane of the host cell [Mol. Microbiol. (1997) 23 1–10]. Replication of the (linear) genome of bacteriophage f29 was mentioned above. In certain phages the rolling circle mechanism is involved in replication (see e.g. SSDNA PHAGE, BACTERIOPHAGE l, BACTERIOPHAGE fX174). [The enzymology of DNA replication (historical perspective): JB (2000) 182 3613–3618.] DNA restriction See RESTRICTION–MODIFICATION SYSTEM. DNA sequencing Any procedure for determining the sequence of nucleotides in a sample of DNA. Sequencing is important in taxonomy, identification and characterization. In the ‘chemical’ (Maxam–Gilbert) method, end-labelled copies of an unknown sequence are cleaved by base-specific reagents; analysis follows electrophoresis of the fragments. The dideoxy (Sanger’s) method is described in the figure on page 249. (See also PYROSEQUENCING.) Automated DNA sequencing is often based on the dideoxy method. Primers are labelled with fluorescent dyes, a different dye being used for each of the four reactions. The products from all four reactions are combined and then subjected to electrophoresis from a single well in a polyacrylamide gel. On excitation by an argon laser, fragments from each reaction mixture can be distinguished from those of other reaction mixtures by their dye-specific emission characteristics; emissions from the fragments of all four reaction mixtures are detected automatically and stored e.g. in digital form. Sequencing provides definitive information on a given sample of nucleic acid. For duplex DNA, greater accuracy is obtained if both strands of the duplex are sequenced. RNA can be retrotranscribed into cDNA; the (single-stranded) cDNA is then amplified, and the amplified product is sequenced. The sequence of nucleotides in the RNA sample is then deduced. Amplified DNA copies of an RNA sample may be obtained by reverse-transcriptase PCR (rtPCR). DNA splicing See CLONING (of DNA). DNA Stat See BLOOD DNA ISOLATION KITS. DNA synthesis See DNA REPLICATION. DNA topoisomerase Syn. TOPOISOMERASE. DNA toroid A highly compacted genomic DNA, found e.g. in Deinococcus radiodurans and ENDOSPORES, which may account at least partly for resistance to DNA-damaging agents (e.g. radiation). Toroidal structure may facilitate repair of doublestranded breaks in a RecA- and template-independent way [JB (2004) 186 5973–5977]. DNA tumour viruses Oncogenic DNA-containing animal viruses; they include members of the ADENOVIRIDAE, Hepadnaviridae (see e.g. HEPATITIS B VIRUS), Herpesviridae (subfamily GAMMAHERPESVIRINAE), and PAPOVAVIRIDAE. DNA unwinding protein Any protein capable of unwinding and separating the strands of double-helical DNA. (See HELICASES; cf. SINGLE-STRAND BINDING PROTEIN.) 248

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TCTGACGTAAGC

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T C T G A C G T A A G C

DNA SEQUENCING: determining the nucleotide sequence of a cloned DNA fragment by the dideoxy method (Sanger’s chain-termination method) (diagrammatic). Initially, the fragment to be sequenced is obtained in single-stranded form (e.g. by cloning in a phage M13 vector). Regardless of the cloning method used, the unknown sequence will be flanked on its 3′ side by single-stranded DNA of known sequence derived from the vector molecule; this permits the design of a labelled primer which can bind at a site next to the unknown sequence such that the first nucleotide to be added to the primer will pair with the first 3′ nucleotide of the unknown sequence. In the diagram, the ‘unknown sequence’ is TCTGACGTAAGC; a primer (short line), which carries a label (black disc), has bound at a site flanking the 3′ end of the unknown sequence. DNA synthesis in vitro is normally carried out with a reaction mixture that includes (i) templates (in this case, single-stranded fragments containing the unknown sequence); (ii) primers; (iii) the four types of deoxyribonucleoside triphosphate (dATP, dCTP, dGTP and dTTP); and (iv) DNA polymerase. When base-paired to the template strand, the primer is extended (5′ -to-3′ ) by the sequential addition of nucleotides as dictated by the template. In sequencing, there are four separate reaction mixtures (G, C, T, A), each containing all the constituents mentioned above (including millions of copies of the unknown sequence, and of the primer). In addition, each mixture contains a given dideoxyribonucleoside triphosphate (ddNTP); thus, the G mixture contains dideoxyguanosine triphosphate (ddG), the C mixture ddC, the T mixture ddT, and the A mixture ddA. When a dideoxyribonucleotide is added to a growing strand of DNA it prevents addition of the subsequent nucleotide because dideoxyribonucleotides lack the 3′ -OH group necessary for making the next phosphodiester bond. Thus, primer extension will stop (= chain termination) at any location where a dideoxyribonucleotide has been incorporated. In each reaction mixture the concentration of ddNTP is such that, in most growing strands, synthesis will be stopped, at some stage, by the incorporation of a dideoxyribonucleotide; because a ddNTP may pair with any complementary base in the template, chain termination can occur at different sites on different copies of the template strand – so that product strands of different lengths will be formed. For example, with ddG (see diagram) the three products are of different lengths because, during extension of the primers, ddG has paired with cytosine residues at three different locations in the template; note that, in this case, the length of a given product strand is related to the location of a particular cytosine residue in the unknown sequence. Analogous comments apply to reaction mixtures containing the other ddNTPs. At the end of the reaction, product strands are separated from templates by formamide. Each reaction mixture is then subjected to electrophoresis in a separate lane of a polyacrylamide gel. Short product strands move further than longer ones, in a given time; products that differ in length by only one nucleotide can be distinguished, the shorter product moving just a little further. The gel contains urea; this inhibits base-pairing between product strands and templates. It also inhibits intra-strand base-pairing in the product strands. This is essential: to deduce the sites of a particular base in the template it is necessary to compare the lengths of all product strands in the given reaction, and this requires proportionality between strand length and electrophoretic mobility; were intra-strand base-pairing to occur it could alter electrophoretic mobility – in which case a product’s length would not necessarily be indicated by the position of its band in the gel. (Continued on page 250.)

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DNA uptake site challenges of producing pure plasmid DNA: TlBtech. (2000) 18 296–305.] [Plasmids for Therapy and Vaccination: Book ref. 225.] (See also GENE GUN.) DnaA boxes See CELL CYCLE (b). dnaA gene A DNA GENE whose product is necessary for the initiation of DNA REPLICATION in bacteria; in archaeans the Orc1 and CdC6 proteins carry out the same function. DnaA proteins bind to 9-bp sequences (‘DnaA boxes’) in the oriC region during initiation (see CELL CYCLE (b)) and this is followed by localized strand separation. Defective (mutant) DnaA proteins have been reported [Mol. Microbiol. (2000) 35 454–462]. DnaA was earlier reported to be needed for the replication of certain plasmids (e.g. pSC101) but is now seen to be specific to the replication of chromosomal DNA. In eukaryotes, the DnaA function is carried out by six proteins (Orc1–6). [Initiators of DNA replication: FEMS Reviews (2003) 26 533–554.] DNAase DEOXYRIBONUCLEASE. dnaB gene A DNA GENE whose product is necessary for many cases of primer formation; in a current model of DNA REPLICATION in Escherichia coli, a hexamer of DnaB proteins functions as a HELICASE – forming part of the PRIMOSOME and unwinding the parent duplex as the primosome migrates with the replication fork. It appears that ATP binding is necessary for the binding of DnaB to ssDNA, while ATP hydrolysis permits its release. In the absence of single-strand binding protein (SSBP), DnaB–ATP can bind to many sites on ssDNA, and interaction with primase leads to the formation of a short RNA primer at each site (general priming); general priming is inhibited by SSBP. Specific priming occurs in the presence of SSBP and depends on the presence of other proteins of the PRIMOSOME. dnaC gene (dnaD gene) A DNA GENE whose product is required for PRIMOSOME formation. dnaD gene Syn. dnaC gene (q.v.). dnaE gene Syn. polC gene (see DNA POLYMERASE). dnaF gene Syn. nrdA gene (q.v.). dnaG gene See PRIMASE. dnaH gene Syn. dnaZ gene (see DNA POLYMERASE). dnaI gene A DNA GENE whose function is required for initiation of DNA REPLICATION at the replication origin. dnaJ gene A DNA GENE which is closely linked to the dnaK gene (q.v.) and which, like dnaK, is necessary for viability of Escherichia coli at high temperatures and apparently for phage l DNA replication. dnaK gene A DNA GENE whose function is essential for the viability of Escherichia coli at high temperatures, and which is also reported to be required for phage l DNA replication. The product of dnaK was identified as protein B66.0, a HEAT-SHOCK PROTEIN. [Properties of DnaK: JBC (1984) 259 8820–8825.]

DNA uptake site (in Haemophilus) See TRANSFORMATION (1). DNA vaccine Any parenterally administered VACCINE consisting of DNA. A DNA vaccine consists e.g. of copies of a PLASMID that encodes specific antigen(s); the encoded antigen(s) are synthesized in vivo (i.e. within the recipient of the vaccine) and may then induce both humoral (antibody) and cell-mediated responses. A DNA vaccine may have prophylactic and/or therapeutic uses. The possibility of using DNA vaccines against the major diseases (malaria, tuberculosis etc.) has attracted much interest. It is known that a DNA vaccine encoding e.g. the 65 kDa heat-shock protein (Hsp65) of Mycobacterium tuberculosis can protect mice against infection by this pathogen; the vaccine appears to stimulate an antigen-specific subset of Th1 T cells which (i) have cytotoxic activity against infected cells, and (ii) secrete interferon-g (IFN-g). More recently, it has been shown that a DNA vaccine encoding Hsp65 can act therapeutically in mice during an experimentally established infection with Mycobacterium tuberculosis [Nature (1999) 400 269–271]. In this study, virulent cells of M. tuberculosis H37Rv were injected intravenously and the infection allowed to develop for 8 weeks. DNA vaccine was then administered in four intramuscular doses at 2-week intervals; each dose of vaccine consisted of 50 µg plasmid DNA in 50 µl saline. Different types of vaccine were used in different groups of animals; the vaccine encoding Hsp65 was found to be significantly more effective than other vaccines encoding different mycobacterial antigens (Hsp70 and ESAT-6). The therapeutic effect of the Hsp65 vaccine (manifested by a marked decrease in the numbers of live tubercle bacilli in lung and spleen) was associated with a switch from a Th-2-dominated to a Th-1-dominated response in the mice. Interestingly, non-methylated CpG regions in the DNA itself can induce secretion of INTERLEUKIN-12 (IL-12) from antigenpresenting cells (such as macrophages). IL-12 is known to promote the development of the Th-1 phenotype in T cells exposed to antigen. Because IL-12 is one of the factors essential for effective immunity to M. tuberculosis in mice, a plasmid encoding IL-12 (rather than a mycobacterial antigen) was tested in the same study [Nature (1999) 400 269–271]; this vaccine was found to cause the maximum reduction in tubercle bacilli by 11 weeks, i.e. its performance exceeded that of the mycobacterial antigens. A DNA vaccine has also been used against Ebola virus: see FILOVIRIDAE. Any future large-scale development/use of DNA vaccines is dependent on appropriate technology for preparing pure plasmid DNA (e.g. free of contaminating chromosomal DNA) in sufficient quantity. [Biochemical engineering approaches to the

DNA SEQUENCING (continued) Bands in the gel are revealed e.g. by staining or chemiluminescence; if the primers carry a radioactive label, the gel is examined by autoradiography following electrophoresis. The locations of bands indicate the relative lengths of product strands – shorter products having moved further down the gel (from top to bottom in the diagram). Note that the first unknown 3′ nucleotide (C) is identified by (i) the shortest product strand (which has moved the furthest), and (ii) the fact that this product is from the ddG mixture – indicating a base that pairs with G, i.e. C. Similarly, the next unknown (G) is the next shortest product strand which came from the ddC mixture, thus indicating G. The entire unknown sequence can be deduced in this way. The figure also shows part of an autoradiograph of a sequencing gel (courtesy of Joop Gaken, Molecular Medicine Unit, King’s College, London). Figure reproduced from Bacteria, 5th edition, Figure 8.23, pages 222–223, Paul Singleton (1999) copyright John Wiley & Sons Ltd, UK (ISBN 0471-98880-4) with permission from the publisher.

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dot-blot Domestos See HYPOCHLORITES. dominance (genetics) In a diploid (or merodiploid) heterozygous cell or organism: the tendency of certain (dominant) alleles to be expressed in preference to their corresponding (recessive) alleles. (cf. EPISTASIS.) The complete dominance of one allele over another occurs in only some cases; in such cases the phenotype of the heterozygote Aa is identical to that of the homozygote, AA (A being dominant). When partial dominance is exhibited the Aa phenotype is intermediate between the AA and aa phenotypes. dominant allele See DOMINANCE. Domiphen bromide See QUATERNARY AMMONIUM COMPOUNDS. DON (1) (6-diazo-5-oxo-L-norleucine; CO2 H.CHNH2 .(CH2 )2 . CO.CH=N+ =N− ) An ANTIBIOTIC and antitumour agent obtained from Streptomyces sp; its mode of action resembles that of AZASERINE. Other antitumour DON derivatives are produced by Streptomyces spp: e.g. diazomycin A (N-acetyl-DON) and alazopeptin (apparently comprising one alanine and two DON residues). (cf. HADACIDIN.) (2) Deoxynivalenol – see TRICHOTHECENES. donation (mol. biol.) See CONJUGATION (1b) (i). donor Any cell or organism which donates genetic information to another cell or organism (the recipient): see CONJUGATION, TRANSDUCTION and TRANSFORMATION. donor conjugal DNA synthesis See CONJUGATION (1b) (i). donor site (of a ribosome) See PROTEIN SYNTHESIS. donor splice site See SPLIT GENE (a). donor-suicide model (for transposition) See e.g. Tn10. Donovan bodies See GRANULOMA INGUINALE. donovanosis Syn. GRANULOMA INGUINALE. L-dopa See MELANIN. Dorisa See EIMERIORINA. Dorisella See EIMERIORINA. dormancy (hypobiosis) The state of an organism or spore which exhibits minimal physical and chemical change over an extended period of time; when no physical or chemical change can be detected the state is sometimes referred to as cryptobiosis. (See also ENDOSPORE (sense 1(a)) and SPORE.) dorsal zone of membranelles See DZM. Dorset’s egg A MEDIUM used e.g. for the maintenance of Mycobacterium spp; it consists of a saline suspension of homogenized whole hens’ eggs which has been inspissated in sloped bijou or universal bottles. dorsiventral Having two unlike (upper and lower) surfaces. dosa A traditional fermented food in India; it is prepared from milled rice and black gram (cf. IDLI). [Microbiology of dosa: Food Mic. (1986) 3 45–53.] dosage (of genes) See GENE DOSAGE. dot-blot A PROBE-based method for detecting or quantifying a specific sequence of nucleotides in a given sample. A drop of the sample is added to a suitable membrane and treated so that any nucleic acids present in the sample bind to the membrane in single-stranded form. The membrane is then exposed to probes (which are complementary to the target sequence) under conditions permitting probe–target hybridization; when unbound probes are removed by washing, the presence of bound probes indicates the presence of the required target sequence. If, for example, the probe had been tagged with DIGOXIGENIN, the bound probe is detected by treating the membrane with a conjugate consisting of anti-digoxigenin (antibody to digoxigenin) covalently linked to an enzyme (such as alkaline phosphatase); the binding of conjugate to digoxigenin is determined by adding a colourgenerating substrate for the enzyme after all unbound conjugate has been removed by washing.

dnaL gene An uncharacterized DNA GENE. dnaM gene An uncharacterized DNA GENE. dnaN gene See DNA POLYMERASE. dnaP gene A DNA GENE whose function is required for initiation of DNA REPLICATION at the replication origin. dnaQ gene See DNA POLYMERASE. DNase DEOXYRIBONUCLEASE. dnaT gene A DNA GENE whose product may interact with DnaC protein in vivo; dnaT mutants cannot destabilize the replication complex at chain termination. dnaW gene Syn. adk gene (q.v.). dnaX gene See DNA POLYMERASE. dnaZ gene See DNA POLYMERASE. dNTP DeoxyriboNUCLEOSIDE-5′ -triphosphate. Dobiella See EIMERIORINA. Dobrava-Belgrade virus See HANTAVIRUS. DOC Dissolved organic carbon. (cf. POC.) docking protein See SIGNAL HYPOTHESIS. D¨oderlein’s bacilli Aciduric, Gram-positive bacilli, probably Lactobacillus sp(p), observed by D¨oderlein (1892) in human vaginal secretions. dodine (dodine acetate; n-dodecylguanidine acetate) An agricultural (non-systemic) ANTIFUNGAL AGENT used e.g. for the control of apple scab – against which it has eradicant as well as protective action. Dodine has the properties of a cationic surfactant. dog (parvovirus infection) See CANINE PARVOVIRUS. dog lichen Peltigera canina. dolichol A polyprenol consisting of 14–24 a-saturated isoprene units; phosphorylated dolichols function in eukaryotes as membrane-bound sugar carriers, assisting the transfer of hydrophilic sugar residues from soluble nucleotide precursors through membranes (e.g. of the rough endoplasmic reticulum and Golgi apparatus) to polymers such as polysaccharides, glycoproteins etc. (see e.g. PALADE PATHWAY). (cf. BACTOPRENOL.) Dolichomastix See MICROMONADOPHYCEAE. doliform (doliiform) Barrel-shaped. dolipore septum A type of SEPTUM present in the hyphae of most basidiomycetes (cf. AMBROSIOZYMA). The central portion of the septum is thickened and barrel-shaped, the septal pore forming a small tunnel (ca. 0.1 µm diam.) through this thickened region. A curved double membrane (the septal pore cap or parenthesome) typically occurs on each side of the septum, these structures appearing (in cross section) as brackets (parentheses) around the septa. The parenthesomes appear to be formed from the endoplasmic reticulum and may be perforate or imperforate; they may serve as screens, regulating the passage of cellular structures between adjacent cells. Parenthesomes are lacking e.g. in Filobasidiella. dollar spot A disease of turf grasses (particularly red fescue, Festuca rubra) caused by Sclerotinia homeocarpa; yellowishbrown patches, up to ca. 8 cm across, develop on the turf in mild, wet weather. domain (immunol.) Any one of the several compact, globular sections of a heavy chain or a light chain in an IMMUNOGLOBULIN molecule; each domain consists of a part of the polypeptide chain which forms a loop (closed by an intra-chain disulphide bond) and which is extensively folded. In IgG the heavy chain domains, in sequence, are designated VH (variable region), and CH 1, CH 2 and CH 3 (constant region); the light chain domains are designated VL and CL . (Domains are also written as e.g. CH1, CH2 etc, or as CH1 , CH2 etc.) domain (taxon.) A category ranked above kingdom [origin of term: PNAS (1990) 87 4576–4579] – see e.g. ARCHAEA and BACTERIA. 251

dot genes downstream box In certain prokaryotic and phage genes: a sequence of nucleotides, downstream from the start site, which has been regarded as a translation enhancer. The ribosomal 16S rRNA may contain a complementary region (called the anti-downstream box ), although suggestions that this may bind to the downstream box have been disputed [JB (2001) 183 3499–3505]. downstream promoter element In some RNA polymerase II PROMOTERS: a region downstream of the start site with a role apparently similar to that of the TATA box. downy mildews Plant diseases caused by certain members of the PERONOSPORALES (e.g. BREMIA, PERONOSPORA, PLASMOPARA); downy mildews are characterized by the formation of superficial hyphal growth in which, typically, individual spore-bearing structures can be distinguished under low magnification. (cf. POWDERY MILDEWS.) Downy mildews can be controlled e.g. with copper-based antifungals or ZINEB. doxycycline See TETRACYCLINES. Dp Pattern difference. In the comparison of two strains by NUMERICAL TAXONOMY: a coefficient which indicates the degree of dissimilarity corrected for any difference(s) due solely to inter-strain differences in metabolic vigour. (cf. entry Sp .) DP Degree of polymerization: the number of monomeric units per molecule of a polymer. DPD N,N-diethyl-p-phenylenediamine (see WATER SUPPLIES). DPN Diphosphopyridine nucleotide: see NAD. DPT A MIXED VACCINE containing diphtheria toxoid, pertussis vaccine and tetanus toxoid. DPX A neutral, synthetic MOUNTANT of refractive index ca. 1.53 when dry; it consists of Distrene and a plasticizer (tritolyl phosphate) dissolved in x ylol. DR DIRECT REPEAT. Dr adhesins A category that includes both fimbrial and nonfimbrial adhesins, members of which are found e.g. on UPEC strains of Escherichia coli; the Dr adhesins bind to CD55 (at a site corresponding to the Dra blood group antigen). draft tube In a LOOP FERMENTER: a wide, vertical tube typically situated coaxially within the column so as to leave an annular space between itself and the wall of the fermenter; when the fermenter is operating, the draft tube is completely submerged in the culture. Culture is made to flow up (or down) the draft tube in order to generate a circulatory flow in the column – culture flowing down (or up) the annulus. DraI See RESTRICTION ENDONUCLEASE (table). Draparnaldia See CHAETOPHORA. draughtsman colony (checker colony) The form of COLONY typically (though not invariably) produced by Streptococcus pneumoniae growing on blood agar: round and raised, with steep sides and a flat top, i.e., resembling one of the pieces used in a game of draughts (= checkers); after overnight growth under a raised partial pressure of CO2 the colonies are each ca. 1 mm in diameter and surrounded by a zone of a-haemolysis. Very young colonies of S. pneumoniae are typically convex (domed); the flattened colony form apparently results from autolysis of the constituent cells on continued incubation, and further incubation may result in the development of a concavity in the upper surface of the colony. draw tube In some microscopes: a tube coaxial with the body tube (see MICROSCOPY) used to adjust the tube length. drd plasmid A mutant CONJUGATIVE PLASMID in which the TRANSFER OPERON is permanently DEREPRESSED. Drechslera A genus of fungi of the HYPHOMYCETES; teleomorphs occur in the genera Cochliobolus and Pyrenophora.

Alternatively, a radioactive probe can be used. For quantification, serial dilutions of the sample are examined as described above; the quantity of target present in the sample can then be assessed by noting the strength of label (i.e. colour, radioactivity etc.) in comparison with that of controls of known concentration. dot genes (of Legionella pneumophila) See end of section (a) in PHAGOCYTOSIS. Dothidea See DOTHIDEALES. Dothideales The largest order of fungi in the subdivision ASCOMYCOTINA; the organisms include saprotrophs, plant parasites and lichenized fungi. Ascocarp: ascolocular (see ASCOCARP and ASCOSTROMA), ostiolate or closed. Asci: bitunicate, cylindrical to spheroidal. Some species exhibit one or more asexual (conidial) stages. Genera: e.g. ARTHOPYRENIA, Cochliobolus (see also DRECHSLERA), Cucurbitaria (syn. Phialospora), DIDYMELLA, Dothidea, ELSINOE¨ , LEPTOSPHAERIA, MYCOSPHAERELLA, Myriangium (see also ASCOSPORE and ASCOSTROMA), Ophiobolus, PIEDRAIA, Pleospora (see also BLACKLEG sense 2), Pyrenophora (see also DRECHSLERA and NET BLOTCH), Sphaerulina (see also NORMANDINA), VENTURIA. (See also BLACK MILDEWS and SOOTY MOULDS.) DOTS Directly observed therapy, short-course: see TUBERCULOSIS. double diffusion (serol.) GEL DIFFUSION in which antigen and antibody both diffuse through the gel (cf. SINGLE DIFFUSION). In one procedure, this is achieved by placing antibody and antigen at opposite ends of a gel column; in the Oakley–Fulthorpe test (double diffusion, single DIMENSION) antibody is incorporated in a layer of gel, and this is separated by a layer of plain gel from the aqueous solution of antigen which is placed on top. (cf. OUCHTERLONY TEST.) double dimension (serol.) See DIMENSION. double fixation See ELECTRON MICROSCOPY (a). double helix See DNA. double lysogen See e.g. TRANSDUCTION. double-negative T cells See T LYMPHOCYTE. double recessive HOMOZYGOUS for a given recessive allele, or alleles. double refraction Syn. BIREFRINGENCE. double-strand break–repair model See RECOMBINATION Fig. 2. (See also RECOMBINATION REPAIR.) double thymidine blockade See SYNCHRONOUS CULTURE. double-vial See FREEZE-DRYING. doubling dilutions See SERIAL DILUTIONS. doubling time See GROWTH (a). Doulton filter See FILTRATION. dourine (mal du coit) A chronic or subacute, often fatal, sexually transmitted disease of equines caused by Trypanosoma equiperdum; it occurs in parts of Africa, America, Asia and Europe. Initial symptoms include oedematous, inflamed lesions of the genitalia, and transient skin lesions (plaques) up to 5 cm in diameter; later symptoms include anaemia and neurological involvement (e.g. paralysis). Quinapyramine and suramin have been used therapeutically. A carrier state occurs. down mutation (down-promoter mutation) A MUTATION in a PROMOTER which results in a decreased level of transcription from that promoter. (cf. UP MUTATION.) downcomer In a LOOP FERMENTER: the descending column of liquid or that part of the fermenter which contains it. (cf. RISER.) downstream (mol. biol.) In, or in relation to, the direction in which a nucleic acid strand or a polypeptide chain is synthesized; the converse of ‘downstream’ is referred to as ‘upstream’. (See e.g. PROMOTER.) 252

Dunaliella DTP Syn. DPT. dualtropic (polytropic) Refers to a recombinant retrovirus derived from an ecotropic virus and a xenotropic virus; the recombinant virus has an extended host range and can, like AMPHOTROPIC viruses, replicate in both homologous and heterologous cells. However, a dualtropic murine virus differs from an amphotropic murine virus in that it possesses env glycoprotein antigenic determinants in common with those of the parental ecotropic and xenotropic murine viruses, and may thus be neutralized by antiserum to the env glycoprotein of either or both of these viruses. [Book ref. 114, p. 73.] (See also MCF VIRUSES.) duck diseases See POULTRY DISEASES. duck embryo vaccine (DEV) See RABIES. duck hepatitis B virus (DHBV) A virus of the HEPADNAVIRIDAE which infects Pekin ducks (Anas domesticus) and other domestic ducks; strains of DHBV have also been detected in wild mallard [JGV (1986) 67 537–547]. DHBV can be transmitted vertically via the egg. Infected ducks commonly exhibit persistent viraemia and may develop chronic liver disease; integrated DHBV DNA has been detected in a hepatocellular carcinoma in a domestic duck [PNAS (1985) 82 5180–5184] (cf. HEPATITIS B VIRUS). duck infectious anaemia virus See AVIAN RETICULOENDOTHELIOSIS VIRUSES. duck plague Syn. DUCK VIRUS ENTERITIS. duck virus enteritis (duck plague) An acute, highly infectious disease of ducks, geese and swans; it is caused by anatid (or anserid) herpesvirus 1 (see HERPESVIRIDAE). Symptoms: loss of appetite, thirst, nasal and ocular discharge, neurological signs; multiple haemorrhages occur in internal organs. Transmission is believed to occur mainly via pond-water. duck virus hepatitis (DVH) An acute disease of young ducklings, caused by an ENTEROVIRUS; older ducks and other birds are not susceptible. Infection occurs by ingestion of food contaminated with faeces of infected birds. Incubation period: 24–48 hours. The disease progresses rapidly and death may occur within one or a few hours. On postmortem examination the liver is found to be enlarged and haemorrhagic. Vaccines are available for prevention; immune serum has been used in treatment. Dulbecco’s PBS Phosphate-buffered saline originally formulated to contain (g/l): NaCl (8.0), KCl (0.2), Na2 HPO4 (anhydrous) (1.15), CaCl2 .2H2 O (0.132), KH2 PO4 (0.2), and MgCl2 .6H2 O (0.1). dulcitol Syn. GALACTITOL. dulse See PALMARIA. Dunaliella A genus of unicellular, naked (wall-less), halotolerant, biflagellated green algae (division CHLOROPHYTA) which closely resemble CHLAMYDOMONAS spp except for their lack of cell wall. Dunaliella spp can grow in aquatic environments of a wide range of salinities, up to and including saturated brines, and are common e.g. in hypersaline environments (salt lakes etc) throughout the world – often forming extensive red or green blooms. The organisms have an exceptional osmoregulatory capacity, using glycerol as an osmoregulator (see OSMOREGULATION); the intracellular concentration of glycerol can be varied rapidly to compensate for changes in the osmotic strength of the surrounding medium. The glycerol can be formed either from stored starch or as a direct product of photosynthetic carbon fixation; a reduction in glycerol concentration apparently occurs by glycerol degradation. When certain species are subjected to hypo-osmotic shock, the cells swell, change shape (from elongated to spherical),

The organisms form septate mycelium and pigmented, septate, commonly cylindrical conidia; conidiogenesis is tretic (see CONIDIUM). Drechslera spp are typically graminicolous (cf. e.g. PHAEOHYPHOMYCOSIS). Species which have been transferred from HELMINTHOSPORIUM to this genus include e.g. D. gramineae, D. maydis, D. oryzae (causal agent of brown spot disease of rice), and D. victoriae (see also VICTORIN). Dreyer’s tube A small, conically-based glass test-tube with a flared rim and an internal diameter of ca. 5 mm; it is used in serology for the clear observation of reactions involving agglutination or precipitation. drift See GENETIC DRIFT and ANTIGENIC DRIFT. DRNA DISSIMILATORY REDUCTION OF NITRATE TO AMMONIA. drop plate method Syn. MILES AND MISRA’S METHOD. droplet infection INFECTION (sense 1) by inhalation of an AEROSOL of saliva, mucus etc. (contaminated with pathogens) from an infected individual. dropsy Syn. OEDEMA. (See also INFECTIOUS DROPSY.) Drosophila A virus See PICORNAVIRIDAE. Drosophila C virus See PICORNAVIRIDAE. Drosophila P virus See PICORNAVIRIDAE. Drosophila X virus (DXV) A virus which causes anoxia sensitivity and death in Drosophila melanogaster and which can be cultivated in Drosophila cell lines [JGV (1979) 42 241–254]. DXV closely resembles IPN VIRUS in morphology, genome etc. (See also SIGMA VIRUS.) drug resistance Syn. ANTIBIOTIC resistance. dry bubble See BUBBLE DISEASES. dry rot (1) (of timber) A BROWN ROT of structural (and other) timbers caused by the cellulolytic fungus Serpula lacrymans; only wood having a moisture content greater than about 20% (see TIMBER SPOILAGE) can be attacked initially, but water produced during metabolism can be transported via moisture-conducting rhizomorphs, enabling the fungus to spread to drier regions of wood (or across brickwork etc). Infected timbers often exhibit longitudinal and cross-grain cracking and a surface growth of whitish mycelium containing yellow and/or lilac patches; the leathery fruiting bodies bear a mass of rust-coloured spores. Control of dry rot involves removal of decayed wood and disinfection of remaining timbers by heat and/or the application of fungicides (see TIMBER PRESERVATION). Infections similar to dry rot may be caused e.g. by Poria spp. (cf. WET ROT.) (2) A storage rot of potato tubers caused e.g. by Fusarium coeruleum ( = F. solani var. coeruleum) and F. sulphureum. The tubers develop dark, sunken lesions which develop into mycelium-filled cavities; affected tubers lose water and shrink, becoming wrinkled and eventually drying into a hard mass. Under humid conditions, however, infection by SOFT ROT organisms may result in rapid decomposition of the tubers. (See also TECNAZENE.) dryad’s saddle Polyporus squamosus (q.v.). drying (1) (of foods) See FOOD PRESERVATION (c). (2) (of plates) See PLATE. (3) (of microorganisms) See DESICCATION. ds (of DNA or RNA) Double-stranded. dsb genes See PROTEIN SYNTHESIS (protein folding). ds(c)DNA Double-stranded circular DNA. DSI stain See DIETERLE SILVER STAIN. DSM Deutsche Sammlung von Mikroorganismen (culture collection of microorganisms), Grisebachstr. 8, D-3400 G¨ottingen, Germany. DTH Delayed-type hypersensitivity: see DELAYED HYPERSENSITIVITY. dTMP Deoxythymidine 5′ -monophosphate [see Appendix V(b)]. 253

Duncan disease 10 distinct dsRNA segments whereas healthy isolates contain 0–4 dsRNA segments, suggesting that specific dsRNA segments may be associated with the development of disease [PP (1986) 35 277–287]. (See also CHESTNUT BLIGHT and MYCOVIRUS.) Duttonella A subgenus of TRYPANOSOMA within the SALIVARIA; species include parasites and pathogens of a range of wild and domestic animals (see e.g. NAGANA). The trypomastigote form typically has a large, terminal kinetoplast and a free flagellum. T. (D.) vivax occurs in the vertebrate in the trypomastigote form (ca. 20–30 µm in length) which divides by longitudinal binary fission; it is transmitted cyclically by Glossina spp – in which epimastigotes and metacyclic forms develop solely in the proboscis. Mechanical transmission by other biting flies (e.g. Tabanus) occurs outside the tsetse belt. T. (D.) uniforme is similar to T. (D.) vivax, though somewhat smaller. Duval’s bacillus Shigella sonnei. Duvenhage virus See LYSSAVIRUS. DVH DUCK VIRUS HEPATITIS. dw Dry weight. dwarf bunt See COMMON BUNT. DWELL See ETRIDIAZOLE. dyad symmetry See e.g. PALINDROMIC SEQUENCE. dye A water-soluble, aromatic compound which has coloured anions and/or cations that can bind to particular substance(s); binding may be primarily ionic but may involve e.g. hydrogenbonding. (See also AUXOCHROME; CHROMOPHORE; LEUCO COMPOUND.) (In microbiology ‘dye’ is often used interchangeably with ‘stain’ to refer not only to dyes, as defined, but also to other substances – e.g. LYSOCHROMES – used for STAINING; ‘stain’ may also refer to a mixture of dyes and/or to the process of using a dye or stain.) An acid dye has a coloured anion which combines with cationic groups. A basic dye has a coloured cation which combines with anionic groups. A neutral dye is a compound of acid and basic dyes in which each ion contains a chromophore. (The pH of a solution of such dyes does not necessarily indicate whether the dye is acid, basic or neutral.) An amphoteric dye is either acidic or basic according to pH. Although dyes are commonly used for STAINING, some have additional uses: see e.g. ACRIDINES, ETHIDIUM BROMIDE, METHYLENE BLUE, TRIPHENYLMETHANE DYES; see also PH INDICATORS, RESAZURIN TEST. Dyes are classified according to the nature of their chromophores. Those based on a (para- or ortho-) quinonoid ring include the TRIPHENYLMETHANE DYES, xanthene dyes (e.g. EOSIN, pyronin), azine dyes (e.g. JANUS GREEN, NEUTRAL RED, NIGROSIN), azine-related dyes (oxazines, e.g. NILE BLUE A; thiazines, e.g. METHYLENE BLUE, thionin, toluidine blue), and HAEMATEIN. Dyes with a chromophore of one or more azo groups (−N=N−) include BISMARCK BROWN, CHLORAZOL BLACK E, CONGO RED and TRYPAN BLUE; Janus green also contains an azo group. Dyes with a nitro group as chromophore include 2,4,6-trinitrophenol (picric acid). dye-buoyant density centrifugation See ultracentrifugation in the entry CENTRIFUGATION. dye test Syn. TOXOPLASMA DYE TEST. Dynabeads Microscopic beads used in magnetic separation: a technique in which a particular type of cell or molecule is separated from a mixture (in the liquid phase) by allowing the required cells or molecules to bind to beads coated with a specific ligand – the beads then being segregated by use of a magnetic field. Dynabeads (Dynal, Skøyen, Oslo, Norway) are microscopic spheres that contain a mixture of iron oxides; they are superparamagnetic, i.e. they do not exhibit magnetic properties until

and lose motility. (In D. salina expansion of the cytoplasmic membrane during swelling is apparently achieved by fusion of the membrane with numerous small membranous vesicles present in the cytoplasm [JCB (1986) 102 289–297].) Some of the shocked cells lose buoyancy and sink; they may then continue to reproduce slowly or remain dormant, but they recover their motility when transferred to a medium of more favourable salinity. It has been suggested that this is a survival strategy whereby the organism can escape from the upper layers of (potentially damaging) low salinity resulting e.g. from rain or land drainage [JEMBE (1985) 91 183–197]. (See also SINGLE-CELL PROTEIN.) Duncan disease Syn. XLP SYNDROME. Duovirus Syn. ROTAVIRUS. duplex DNA Double-stranded DNA. duplex PCR See MULTIPLEX PCR. duplex winding number See DNA. Durham shelter (gravity slide sampler) An instrument used for sampling airborne particles, particularly pollen. (See also AIR). Essentially it is an adhesive-coated microscope slide mounted horizontally inside a ‘shelter’ consisting of two parallel metal discs joined together by three equidistant 10-cm struts; the upper disc acts as a rain shield. Particle deposition is greatly affected by e.g. the speed and direction of the wind and by turbulence, and the volume of air sampled is unknown. Durham tube A transparent glass tube (2–4 cm long, internal diam. ca. 3–4 mm), closed at one end, used to detect gas production by microorganisms during growth in a liquid medium. An inverted Durham tube is placed in a test-tube of liquid medium before sterilization; when the medium is autoclaved all the air is driven from the Durham tube which thus sinks to the bottom of the test-tube. On inoculation and incubation, any gas formed is trapped in the Durham tube. Durvillaea See PHAEOPHYTA. Dutch elm disease A disease of elm trees (Ulmus spp) caused by Ceratocystis ulmi. In the 1970s/1980s a new aggressive strain of C. ulmi caused massive epiphytotics, destroying millions of elms throughout Europe, SW Asia and North America. The disease is spread by bark beetles of the Scolytidae (commonly Scolytus spp) in a complex series of interactions [review: Book ref. 77, pp. 271–306]. Essentially, adult beetles, carrying C. ulmi propagules, emerge during the spring and summer and feed in the tops of healthy trees; the beetles feed in the crotches of young twigs, and some of the resulting wounds become contaminated with C. ulmi. The pathogen develops and spreads within the xylem vessels (‘pathogenic phase’) and infected twigs wilt and show characteristic streaks or spots; TYLOSES are formed, and the whole tree may die within months. The inner bark (phloem) of dying and dead trees becomes a suitable breeding ground for the scolytid beetles. Female beetles excavate extensive breeding galleries in the bark. C. ulmi colonizes these galleries (‘saprotrophic phase’) and sporulates abundantly (forming conidia, including synnematospores, and ascospores) during the autumn and winter when the larvae are developing. The new generation of adult beetles, carrying spores of C. ulmi, emerges the following year to feed in the twigs of healthy trees, thus completing the cycle. Various ‘diseased’ strains of C. ulmi, characterized by abnormal or reduced growth and impaired reproductive fitness, have been isolated. The disease is apparently caused by an infectious agent, called a ‘d factor’ (for disease factor), which is spread between mycelia by hyphal fusion during the bark stage of the fungus; it has been found that certain diseased isolates contain 254

dysentery placed in a magnetic field. The beads can be coated with any of a variety of ligands – the particular type used depending on the required cell or molecule. For example, if beads are coated with the oligonucleotide T-T-T-T-T-T-T they will bind the poly-A tails of mRNA molecules; this approach can be used to separate mRNAs from total RNA. Essentially, the beads are well dispersed within the sample by thorough mixing; the required cells or molecules bind to the beads – which are then drawn to one side of the vessel by a magnetic field. Unwanted material is discarded, and the required cells/molecules can be washed etc. prior to use. (Note that permanently magnetic beads would not be suitable: they would clump together rather than disperse within the sample.) Beads coated with specific antibodies are useful for isolating particular pathogens – E. coli O157, Salmonella spp, Listeria monocytogenes etc. – from food or other specimens; the bead–pathogen complex can be plated on a suitable medium. This approach can also be used to isolate a specific type of eukaryotic cell from a mixture of cells. This method is called immunomagnetic separation (IMS). Examples of use include: enrichment of Mycobacterium paratuberculosis in milk [AEM (1998) 64 3153–3158]; detection of E. coli O157 in meat [LAM (1998) 26 199–204]; preparation of human glomerular endothelial cells for use in tests with E. coli verocytotoxin [Kidney International (1997) 51 1245–1256]; detection of specific mycobacterial DNA prior to PCR (‘sequence capture’ PCR) [JCM (1996) 34 1209–1256]. dynein See FLAGELLUM (b). dysentery A disease characterized by inflammation of the intestine (particularly the colon), abdominal pain, and frequent passage of fluid stools that may contain blood, mucus and/or pus. ‘Dysentery’ (rather than DIARRHOEA) is the term generally used to refer to a diarrhoeal condition in which (i) blood/mucus is typically present in the stool, and (ii) the intestinal epithelium is actively invaded by the causative organism (as is the case with e.g. Shigella dysenteriae, enteroinvasive E. coli and Entamoeba histolytica). (1) (med.) (a) Bacillary dysentery. The classical (severe) form of dysentery is caused by Shigella dysenteriae serotype 1 (found mainly in tropical countries); somewhat less severe disease is caused by S. sonnei (a common causal agent in temperate zones), S. boydii (mostly tropical) and S. flexneri. As well as the shigellosis, caused by Shigella spp, bacillary dysentery can be caused e.g. by EIEC. Dysentery caused by S. dysenteriae type 1 is transmitted via the faecal–oral route – commonly via food or water contaminated with faeces from patients with dysentery (or from a carrier of the pathogen). Incubation period: 1–6 days. Onset is abrupt, with fever followed by diarrhoea and abdominal cramps. S. dysenteriae proliferates in the gut lumen and invades the epithelium of the terminal ileum and colon. While dysentery due to S. sonnei and S. boydii is typically self-limiting (lasting days), that caused by S. dysenteriae may cause ulceration of the intestinal mucosa and may last for weeks, leading to exhaustion and anaemia; mortality may be high in untreated cases. In animal studies, Shigella is taken up via the so-called ‘M cells’ in Peyer’s patches [M cells in infection (review): TIM (1998) 6 359–365]; from this location the bacteria can spread from cell to cell within the epithelial layer. Such spreading (an essential feature of dysentery) depends on the presence of a (plasmid-encoded) outer membrane protein: IcsA (= VirG). (IcsA is the a-domain of an autotransporter: see type IV secretory systems in PROTEIN SECRETION. An analogous

protein occurs in EIEC.) IcsA promotes actin-based motility: i.e. it induces polymerization of actin filaments at one pole of the cell – forming a growing ‘tail’ of actin which propels the bacterium (through the host cell cytoplasm) in a direction opposite to that of the developing tail. The tail remains stationary within the host cell: ongoing deposition of actin causes bacterial motility. The motile bacterium pushes into the wall of the adjacent cell, either forming a pocket or becoming enclosed within a vacuole (bounded by a double membrane); Shigella lyses the membranes, thus entering the adjacent cell. Mutants lacking a functional IcsA do not spread, and do not cause dysentery. Shigella taken up by M cells may be engulfed by macrophages which occur beneath the M cells. Shigella can kill macrophages (see APOPTOSIS), and in the resulting inflammatory response PMNs may migrate between epithelial cells to reach the gut lumen; such migration is likely to expose basolateral surfaces of epithelial cells to invasion by Shigella [TIM (1997) 5 201–204]. Shigella can induce uptake by the so-called ‘trigger mechanism’, invasion apparently occurring via the basolateral surfaces of epithelial cells; the bacterial adhesin(s) are unknown, but epithelial cell receptors may include integrins (which occur on basolateral surfaces). Invasion involves a type III secretory system (see PROTEIN SECRETION) encoded by the plasmid-borne mxi-spa genes. The same plasmid also encodes IpaA; this protein is translocated to the epithelial cell where it induces certain changes (e.g. actin polymerization) needed for uptake. During uptake (macropinocytosis), the bacterium is engulfed by extrusions of host cell membrane which are supported by actin microfilaments. The bacterium thus induces its own uptake; moreover, the host cell’s GTPase ‘Rho’ also appears to be required. Following uptake (into a vacuole), Shigella lyses the membrane and escapes into the host cell’s cytoplasm; such lysis may involve the (plasmid-encoded) IpaB protein. Cell-to-cell translocation within the epithelial layer can then occur as described above. [Invasion of host cells by Shigella and subsequent inflammation: FEMS Reviews (2001) 25 3–14.] Shigella dysenteriae serotype 1 produces SHIGA TOXIN (q.v.); the role of this toxin in dysentery in not fully understood, but it may be at least partly responsible for the vascular damage and bloody stools. Lab. diagnosis. Culture from stool, or rectal swab, followed by serological typing; colicin and/or phage typing may also be useful. Treatment. Antiobiotics (when indicated, and in accordance with results from susceptibility tests); fluid and electrolyte replacement. (See also ORAL REHYDRATION SOLUTION.) (b) Amoebic dysentery (amoebiasis) is caused by Entamoeba histolytica (see ENTAMOEBA). Infection follows ingestion of cysts from the faeces of patients or carriers. Following excystment, the organisms localize in the large intestine and attack the mucosa; establishment of infection apparently requires the presence of normal gut bacteria (see GASTOINTESTINAL TRACT FLORA). Symptoms range from mild, intermittent diarrhoea to severe, and occasionally fatal, dysentery with blood and mucus in the stools. (Trophozoites produce cyto/enterotoxin(s) [Inf. Immun. (1985) 48 211–218].) Chronic relapsing cases, particularly in endemic regions, may be associated with the development of tumour-like granulomatous masses (called amoebomas) in the large intestine. Severe amoebic dysentery may be associated with amoebic hepatitis (apparently not due to amoebic invasion of the liver). The parasite may also cause abscesses, usually in the liver but also in the lungs, brain etc.; the presence of viable 255

dysgonic (2) (vet.) See e.g. LAMB DYSENTERY, SWINE DYSENTERY, WINTER (cf. SCOURS.) dysgonic See EUGONIC. dyskinetoplasty In e.g. certain naturally-occurring strains of Trypanosoma evansi : the absence of a normal KINETOPLAST – the mitochondrion containing, instead, a small, spherical, electrondense body, the ‘kinetoplast remnant’, which is not visible in Giemsa-stained preparations. Dyskinetoplastic strains of T. evansi and other trypanosomes can be obtained by exposure to e.g. Berenil. dysphotic zone See PHOTIC ZONE. dyspnoea (dyspnea) Difficult or laboured breathing. Dysteria See HYPOSTOMATIA. DZM Dorsal zone of membranelles: a SYNCILIUM (or syncilia) occurring in the anteriodorsal region of some ciliates, e.g. Diplodinium, Epidinium.

amoebae in patients with high titres of antibodies may be at least partly explained by the ability of amoebae to shed aggregates of absorbed antibodies (‘caps’ – see CAPPING sense 3) [JID (1986) 153 927–932]. Lab. diagnosis involves e.g. demonstration of trophozoites and/or cysts in stools or lesions. (See also FLOTATION.) Chemotherapy: see AMOEBICIDE. (c) Balantidial dysentery (balantidiasis) is a severe, sometimes fatal, dysentery caused by Balantidium coli (see BALANTIDIUM). Infection follows ingestion of cysts in food or water contaminated with infected swine faeces. Excystment occurs in the gut; trophozoites cause extensive ulceration of the colon mucosa. Lab. diagnosis: identification of trophozoites or cysts in faeces. Chemotherapy: e.g. diiodoHYDROXYQUINOLINE.

DYSENTERY.

1. Words in SMALL CAPITALS are cross-references to separate entries. 2. Keys to journal title abbreviations and Book ref. numbers are given at the end of the Dictionary. 3. The Greek alphabet is given in Appendix VI. 4. For further information see ‘Notes for the User’ at the front of the Dictionary.

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Dictionary of Microbiology and Molecular Biology, Third Edition Paul Singleton and Diana Sainsbury © 2006 John Wiley & Sons Ltd. ISBN: 0-470-03545-5

E E (1) See REDOX POTENTIAL. (2) Glutamic acid (see AMINO ACIDS). E-cadherin See CADHERINS. E. coli An abbreviation which usually refers to the bacterium Escherichia coli (see entry ESCHERICHIA) but which is also used e.g. for the protozoan Entamoeba coli. (This illustrates the need to ensure that the name of a genus is spelt out in full – on first usage – before using an abbreviated form.) ∗ E precursor cells (immunol.) Cells on whose surface COMPLEMENT FIXATION has occurred, at 4° C, but which do not lyse unless the temperature is raised; lysis can be further inhibited, even at higher temperatures, by EDTA or zinc or uranyl salts. E protein See F PLASMID. E-selectin Syn. CD62E. E site (of a ribosome) See PROTEIN SYNTHESIS. E test A diffusion test for determining the MIC of a given bacterial strain with respect to particular antibiotic(s). One side of a plastic strip (placed in contact with the inoculated plate) carries a given antibiotic, the concentration of which decreases uniformly from one end of the strip; the other side of the strip is graduated with the concentration of antibiotic. Following incubation, the MIC is read by noting the lowest concentration of antibiotic (on the scale) which corresponds to inhibition of growth. Several strips, each with a different antibiotic, can be used simultaneously on a standard-sized plate. The E test has been used for various bacteria, including Pseudomonas aeruginosa [JCM (1991) 29 533–538] and [Helicobacter pylori [JCM (1997) 35 1842–1846]. [Mycobacterium tuberculosis: JCM (2002) 40 2282–2284.] E0 (E0 ) See REDOX POTENTIAL. E′0 See REDOX POTENTIAL. (E1 E2 )-type H+ -ATPase See PROTON ATPASE. e14 element See RECOMBINATIONAL REGULATION. E5531 See ENDOTOXIC SHOCK. EA Erythrocyte–antibody (see e.g. HAEMOLYTIC SYSTEM). (cf. EAC.) EAC Erythrocyte–antibody–complement. EAC 142 . . . indicates that COMPLEMENT components 142 . . . have been fixed. (cf. EA.) eae gene See PATHOGENICITY ISLAND. EAEC (1) ENTEROADHERENT E. COLI [RMM (1995) 6 196–206]. (2) Enteroaggregative E. coli (see EAGGEC) [MR (1996) 60 167–215 (p. 186)]. EAF plasmid See PATHOGENICITY ISLAND and BUNDLIN. EAggEC Enteroaggregative Escherichia coli: strains of E. coli associated with persistent diarrhoea – usually (though not exclusively) in children in the developing countries. (See also ENTEROADHERENT E. COLI.) The organisms form toxins and adhesins, but the mechanism of pathogenesis is unknown. EAggEC may be particularly important as pathogens for undernourished/immunosuppressed patients. [Enteroaggregative and diffusely adherent E. coli: RMM (1995) 6 196–206.] Strains of O111:H12 in Brazil were reported to have the properties of EAggEC [FEMS (1997) 146 123–128]. (See also EAEC and EAST 1.) Eagle’s medium Any of a number of growth or maintenance media (used in TISSUE CULTURE) consisting basically of EARLE’S BSS or HANKS’ BSS supplemented with e.g. amino acid(s), vitamin(s), antibiotic(s), serum etc. ear microflora The microflora of the human ear (external auditory canal) commonly includes e.g. strains of Staphylococcus,

Corynebacterium, Mycobacterium and various yeasts. (See also BODY MICROFLORA.)

Earle’s BSS Earle’s BALANCED SALT SOLUTION; it contains (g/l): NaCl (6.8), KCl (0.4), MgSO4 .7H2 O (0.2), NaH2 PO4 .2H2 O (0.158), CaCl2 .2H2 O (0.264), NaHCO3 (2.2), glucose (1.0), and phenol red (0.01); pH: 7.6–7.8. early blight (of potato) A POTATO DISEASE caused by Alternaria solani. Small dark spots appear on leaves, each spot having concentric rings of necrotic tissue which give a characteristic ‘target’ appearance; tubers may exhibit a superficial brown, dry, corky rot. early genes See VIRUS. earth balls See SCLERODERMATALES. earth stars See LYCOPERDALES. earth tongues Fruiting bodies of species of e.g. Geoglossum or Trichoglossum. East Coast fever An East African tick-borne disease of cattle caused by species of THEILERIA; T. parva and T. lawrencei cause a febrile disease which is usually fatal, while T. mutans typically causes non-febrile anaemia which may be fatal. After the tick vector has ingested blood from an infected bovine host, sexual stages of Theileria appear in the tick’s gut; zygotes develop in the gut, and each forms a motile kinete which migrates to the tick’s salivary glands and undergoes schizogony to form infective sporozoites. The tick can then infect a fresh bovine host. In the new (vertebrate) host the parasite grows in fixed and/or circulating lymphoid cells and forms macroschizonts (‘Koch’s blue bodies’; ‘blue bodies’): schizonts, 10–20 µm in size, whose cytoplasm stains blue with Giemsa’s stain. Subsequently, intra-erythrocytic forms (‘piroplasms’) of T. parva (or T. mutans) become common, but may be scanty/undetectable in T. lawrencei. T. parva and T. lawrencei infections usually kill after 15 days. [Life cycles of Babesia and Theileria: AP (1984) 23 37–103. Anti-T. parva vaccine: Annals New York Acad Sci (2000) 916 464–473.] EAST 1 A heat-stable toxin secreted e.g. by EAGGEC, many strains of EHEC O157:H7, and by Yersinia enterocolitica; it is an analogue of the endocrine hormone guanylin (which stimulates fluid outflow from the intestinal mucosa by activating guanylyl cyclase). eastern equine encephalomyelitis (EEE; eastern equine encephalitis; eastern encephalitis) An acute ENCEPHALITIS (or encephalomyelitis) of man and horses, caused by an ALPHAVIRUS; it occurs in eastern North America, the Caribbean, and parts of Central and South America. EEE virus can also cause disease in domestic birds (pigeons, pheasants). The virus occurs in wild birds, in which transmission occurs mainly via Culiseta melanura; other mosquitoes (e.g. Aedes spp) may be responsible for the sporadic transmission of EEE to animals and man. In man, the mortality rate may be ca. 25–70% or higher. Epizootics in horses may be controlled by vaccination. Eaton’s agent Mycoplasma pneumoniae. EB ELEMENTARY BODY. EB virus EPSTEIN–BARR VIRUS. EBERs (EBV) See EPSTEIN–BARR VIRUS. ebna genes (EBV) See EPSTEIN–BARR VIRUS. Ebola virus See FILOVIRIDAE. EBV EPSTEIN–BARR VIRUS. 257

EC EC (1) Energy charge (See ADENYLATE ENERGY CHARGE). (2) Enzyme Commission (see ENZYME). ECA ENTEROBACTERIAL COMMON ANTIGEN. ecad A distinct population, within a given species, which has adapted phenotypically to its environment. (cf. ECOTYPE.) ecchymosis See PURPURA. Eccrinales See TRICHOMYCETES. ecdysis The shedding of an outer layer: e.g., the exoskeleton of an invertebrate, or the theca in certain DINOFLAGELLATES. Echinamoeba See AMOEBIDA. echinocandin B See ACULEACIN A. echinomycin See QUINOXALINE ANTIBIOTICS. Echinosporangium See MUCORALES. Echinosteliales See MYXOMYCETES. Echinosteliopsidales See MYXOMYCETES. Echinosteliopsis See MYXOMYCETES. Echinostelium A genus of slime moulds (class MYXOMYCETES) which form protoplasmodia and small, stalked sporangia (ca. 1–2% (w/v) forms a gel on cooling below ca. 28–35° C; gels of ca. 4–12% are used e.g. to test the ability of certain microorganisms to liquefy (i.e., hydrolyse) gelatin (see GELATINASE). (See also FRAZIER’S MEDIUM.) gelatinase A GELATIN-hydrolysing enzyme. Gelatin can be hydrolysed (to soluble oligopeptides) by clostridial COLLAGENASES and by any of a range of extracellular proteolytic enzymes produced e.g. by various bacteria and fungi. The activity of many gelatinases requires, or is stimulated by, calcium ions. Gelbstoff Collectively, the various dissolved and colloidal organic substances which occur e.g. in lakes and coastal waters and which may absorb significant amounts of light – particularly at the blue end of the spectrum.

Geleia See KARYORELICTID GYMNOSTOMES. Gelidium See RHODOPHYTA. gellan gum An extracellular polysaccharide produced by ‘Pseudomonas elodea’. Gellan gum is a linear polymer containing residues of glucose, rhamnose and glucuronic acid which may be mainly (1 → 4)-b-linked; the polymer may be O-acetylated. In water containing monovalent or divalent cations, gellan gums form gels on heating and cooling; the nature of the gel depends on the degree of acetylation – the more de-acetylated the polymer the firmer and more brittle the gel. A clarified, de-acetylated form of gellan gum (Gelrite; Keloc, San Diego, USA) can be used as a substitute for AGAR in bacteriological media; the setting temperature varies from 35° C to >50° C, depending on the concentrations of Gelrite and cations. The gels can be re-melted under standard autoclaving conditions. Gelrite gels containing 0.1% calcium chloride are not prone to SYNERESIS at high temperatures (unlike agar gels) and may thus be suitable for use in media for thermophiles. Gelrite may also be used e.g. as a substitute for agarose in gel electrophoresis (Gelrite gels are clearer than agar gels). Gelrite has been investigated for use as a gelling agent, in place of agar, in transport media used for PCR-based studies. This investigation was prompted by the finding that agar inhibits PCR in a concentration-dependent manner [JCM (1998) 36 275–276], an observation suggesting that detection of pathogens by PCR can be inhibited by the use of an agar-containing transport medium (such as STUART’S TRANSPORT MEDIUM). These studies yielded superior results from gellan gum, inhibition of PCR occurring with agar [JMM (2001) 50 108–109]. In industry, the polymer may be useful e.g. as a substitute for pectins or gelatin in jams, jellies etc. or as a matrix for the IMMOBILIZATION of cells or enzymes. [Book ref. 62, pp 231–253.] Gelman filter See FILTRATION. Gelrite See GELLAN GUM. gelsolin See ACTIN. Gemella A genus of Gram-type-positive bacteria of the family Streptococcaceae; the organisms occur e.g. in the mammalian respiratory tract. Cells: cocci (diam. 100 times more effective against rabbit RBCs than human RBCs. It appears to bind to the cell membrane, causing release of K+ – possibly due to the formation of transmembrane pores by amphiphilic hexamers of the haemolysin. a-Haemolysin can be lethal for man and animals; depending on animal species, it can be leucocidal (= the Neisser–Wechsberg LEUCOCIDIN), can aggregate and lyse blood platelets, and has a range of toxic effects e.g. on the nervous and vascular systems (e.g. it increases vascular permeability). When injected subcutaneously it can have dermonecrotic effects which may be due to direct necrotizing activity or to prolonged vasospasm. a-Haemolysin has been shown to play a major role in the pathogenesis of gangrenous mastitis in sheep and cattle. b-Haemolysin (b-toxin) is a SPHINGOMYELINASE C specific for sphingomyelin (or lysolecithin); it is inactivated at 60° C, requires Mg2+ for activity, and is inhibited e.g. by Zn2+ and chelating agents. It can hydrolyse the sphingomyelin in sphingomyelin-rich RBCs (e.g. those from sheep or ox) without causing haemolysis; however, lysis can subsequently be induced by chilling (see HOT–COLD LYSIS) or by the addition of the CAMP factor (see CAMP TEST). b-Haemolysin is most frequently produced by staphylococci isolated from animals other than man. Reports that it can be lethal are controversial. It is not dermonecrotic (although it may cause necrosis in lactating mammary gland), but it can show toxic effects on the cardiovascular

system and can lyse platelets and guinea-pig macrophages (but not human PMNs). Its role in pathogenesis, if any, is unknown. g-Haemolysin (g-toxin) consists of two protein components which appear to act synergistically in bringing about haemolysis. Rabbit RBCs are more susceptible than human or sheep RBCs; horse RBCs are insensitive. g-Haemolysin can also increase membrane permeability in cultured fibroblasts, and may have some leucocidal activity. It is inactivated at 60° C and by certain acidic polymers – including agar, heparin, and dextran sulphate (but not e.g. agarose, hyaluronic acid or chondroitin sulphate), by various lipids (e.g. cholesterol, fatty acids), and by EDTA and citrate. d-Haemolysin (d-toxin) is a heat-stable, hydrophobic, strongly surface active peptide containing 26 amino acid residues. It can lyse RBCs from many (possibly all) species; it is also active on a wide range of natural and synthetic membranes, lysing e.g. leucocytes, all kinds of mammalian cells in culture, certain bacteria, mitochondria, protoplasts, liposomes, etc. At relatively high concentrations, it probably exerts its effect by non-specific solubilization of membrane lipids and/or proteins; at low concentrations it may act by forming transmembrane pores and/or by activating endogenous phospholipase A2 . It is inhibited by various phospholipids and serum lipoproteins, and is poorly antigenic. Different d-haemolysins are produced by different biotypes of S. aureus. [Reviews: Book ref. 44, pp. 619–744.] (f) Streptococcus haemolysins. See e.g. STREPTOLYSIN O and STREPTOLYSIN S. (g) Vibrio parahaemolyticus haemolysin. See KANAGAWA PHENOMENON. haemolysis The lysis of erythrocytes (red blood cells). Haemolysis may occur in any of the following ways. (a) By the action of a COMPLEMENT-dependent or -independent HAEMOLYSIN. (b) By a complement-fixing union between an antibody and an erythrocyte-bound particulate antigen (passive haemolysis). (c) By REACTIVE LYSIS. (d) By osmotic lysis in a hypotonic medium. (e) By viral activity: certain viruses (e.g. the mumps virus) can lyse the erythrocytes of certain species. The ability of certain microorganisms to cause haemolysis can be detected e.g. by growing the organisms on a suitable BLOOD AGAR; an extracellular haemolysin causes the development of a differentiated zone around each colony. Some types of haemolysin bring about a glass-clear, colourless zone. Such clear haemolysis is often called ‘b-haemolysis’; however, ‘b-haemolysis’ can be a misleading term since clear haemolysis can be caused e.g. by the a-haemolysin of staphylococci or by the a- or b-haemolysins of Escherichia coli. A zone in which the blood is greenish, but still opaque, is often called ‘a-haemolysis’; such greening can be caused by various types of haemolysin. The absence of haemolysis is sometimes called (confusingly) ‘g-haemolysis’. haemolytic immune body (HIB; amboceptor) Antibody to the surface antigens of erythrocytes. (See also HAEMOLYTIC SYSTEM.) haemolytic system In a COMPLEMENT-FIXATION TEST: a suspension of sensitized erythrocytes, i.e. erythrocytes (commonly sheep erythrocytes) which have been exposed to a subagglutinating dose of antibodies homologous to their surface antigens. The system exhibits no HAEMOLYSIS in the absence of COMPLEMENT, and almost complete haemolysis (ca. 90% of the erythrocytes lysed) when exposed to the maximum concentration of complement used in a CFT; with amounts of complement between these extremes, the proportion of erythrocytes which lyse is dependent on the amount of free (i.e. unfixed) complement. Thus, the 352

Haemophilus haemolytic system indicates the amount of complement (if any) remaining unfixed in each dilution at the end of the first stage in a CFT. (See also EAC.) haemolytic uraemic syndrome (HUS) A potentially fatal disease (of children and adults) involving renal impairment/acute renal failure (see also TNF). An early stage of (bloody) diarrhoea is common, though not invariably present. Most cases with prodromal diarrhoea appear to be caused by O157 strains of Escherichia coli (see EHEC) or by Shigella dysenteriae. The major symptoms of HUS are toxin-dependent; attempts are being made to sequester toxins in the gut (see SYNSORB Pk ). Complications may include e.g. CNS involvement. Antibiotics have not been found useful, and may be actually harmful. Non-diarrhoeal HUS is sometimes associated with EHEC but may be induced by certain drugs (e.g. mitomycin C, quinine), and there are several other distinct causes. haemophagocytic syndrome (HS) A syndrome which is characterized by fever and e.g. (commonly) cytopenia, coagulopathy, hepatosplenomegaly and haemophagocytosis – i.e. phagocytosis of haemopoietic cells by HISTIOCYTES. Primary HS is associated with inherited conditions. Secondary HS may be associated with certain infections, malignancy or non-malignant conditions (e.g. autoimmune disease), or may be drug-associated (phenytoin). Infection-associated HS (IAHS) includes virus-associated HS (VAHS) and bacterium-associated HS (BAHS). The pathogenesis of HS is not understood but it appears to involve unregulated T lymphocytes, monocytes, macrophages and cytokines; elevated levels of e.g. IFN-g (interferon-g) and IL-18 (interleukin-18) have been found in serum, and an imbalance in Th1/Th2 cells has also been reported. Some 60% of cases have been reported to occur in patients with preexisting immunodeficiency, suggesting that immune status may be important as a predisposing factor. Diagnosis includes demonstrating phagocytosis of erythrocytes (red blood cells), leukocytes and platelets by examination of bone marrow. Microorganisms associated with HS include: Epstein–Barr virus (apparently responsible for most cases of VAHS) and other herpesviruses (e.g. cytomegalovirus, HHV6 and HHV8); species of Borrelia, Brucella, Mycobacterium, Rickettsia, Staphylococcus and Streptococcus; Cryptococcus; and Leishmania donovani. [Haemophagocytic syndrome associated with infections: BCH (2000) 13 163–178.] Haemophilus A genus of Gram-negative bacteria of the PASTEURELLACEAE. Cells: pleomorphic coccobacilli, rods (often ca. 0.4 × 1–2 µm) or – especially under suboptimal growth conditions – filaments. Some strains have capsules. Fimbriae occur in haemagglutinating strains (H. parasuis, H. paragallinarum, strains of H. aegyptius). Optimum growth temperature: 35–37° C. Growth may require the X FACTOR and/or the V FACTOR (see PORPHYRIN TEST and SATELLITE PHENOMENON). Media for primary isolation include e.g. CHOCOLATE AGAR, FILDES’ ENRICHMENT AGAR, or LEVINTHAL’S MEDIUM; some species (e.g. H. ducreyi, H. parasuis) require serum. Growth in some species (e.g. H. aphrophilus, H. paragallinarum) requires, or is enhanced by, incubation with 5–10% CO2 . Colonies on rich media are usually non-pigmented or slightly yellowish, 0.5–2.0 mm diameter (48 hours/37° C); those of capsulated strains are more mucoid and may appear iridescent in obliquely transmitted light. Most species produce acetic, lactic and succinic acids (usually without gas) from glucose. Most strains do not ferment lactose. NO3 − is reduced to NO2 − ; NO2 − may also be reduced. GC%: 37–44. Type species: H. influenzae.

Haemophilus spp are parasitic on the mucous membranes (particularly of the respiratory tract) in man and other animals. Some species are pathogenic; others can be opportunist pathogens, causing e.g. dental abscesses, ENDOCARDITIS etc. Some strains form IgA1 proteases (q.v.). Plasmid-mediated antibiotic resistance has become common in some species (e.g. H. influenzae). H. actinomycetemcomitans. See ACTINOBACILLUS. H. aegyptius. Causes e.g. PINK-EYE, mainly in hot climates. Requires X FACTOR (q.v.) and V factor. Indole −ve; urease +ve; non-haemolytic; usually forms acid (no gas) from glucose but not from xylose; catalase +ve. H. ducreyi. Causes CHANCROID. Requires X factor but not V factor. Indole −ve; urease −ve; non-capsulated; some strains weakly haemolytic; sugars are generally not metabolized (acid from glucose may be delayed +ve); peptidases are produced; catalase −ve. H. influenzae. Parasitic and pathogenic in man. Requires V and X factors; non-haemolytic; acid (no gas) from glucose and xylose; catalase +ve. Eight biotypes (I–VIII) are distinguished e.g. on indole, urease and ODC reactions. Some strains have

Haemophilus influenzae: differentiation of biotypes Biotype I II III IV V VI VII VIII a

Indole

Urease

ODCa

+ + − − + − + −

+ + + + − − − −

+ − − + + + − −

Ornithine decarboxylase test (see

DECARBOXYLASE TESTS).

capsules, and six serotypes are distinguished on the basis of capsular antigens (polysaccharides, at least some of which contain ribosyl groups). Strains of serotype b (usually biotype I) may cause acute diseases such as CELLULITIS, EPIGLOTITIS, MENINGITIS (in children), and PNEUMONIA (caused also by other serotypes). Antisera to serotype b cross-react with antigens from a wide range of bacteria – e.g. staphylococci, streptococci, Bacillus spp. Non-capsulated strains (usually biotypes II or III) occur as commensals (e.g. in the nasopharynx) but can occasionally cause chronic conditions such as BRONCHITIS, CONJUNCTIVITIS, OTITIS MEDIA and SINUSITIS. [Conjugate vaccine against H. influenzae type b (for protection against e.g. meningitis and epiglottitis); RMM (1996) 7 231–241.] H. paragallinarum (including strains formerly called H. gallinarum). Causes coryza in fowl. Requires V factor but not X factor. Indole −ve; urease −ve; non-haemolytic; acid (no gas) from glucose and (some strains) xylose; catalase −ve. H. parainfluenzae. Commensal in man, occasionally implicated in e.g. endocarditis. Requires V factor but not X factor. Indole −ve; urease −ve (biotype I) or +ve (biotypes II and III); non-haemolytic; acid (±gas; biotype III: no gas) from glucose but not from xylose; catalase +ve/−ve. H. parasuis (including most strains formerly called H. suis or H. influenzae-suis). Causes GLASSER’S DISEASE in pigs. Requires 353

haemoproteins V factor but not X factor. Indole −ve; urease −ve; nonhaemolytic; acid (no gas) from glucose but not from xylose; catalase +ve. H. piscium. A fish pathogen (see ULCER DISEASE) now regarded as an atypical strain of Aeromonas salmonicida. H. vaginalis: see GARDNERELLA. Other species: H. aphrophilus, H. avium, H. haemoglobinophilus, H. haemolyticus, H. paracuniculus, H. parahaemolyticus, H. paraphrohaemolyticus, H. paraphrophilus, H. pleuropneumoniae, H. segnis. Species incertae sedis: ‘H. somnus’, ‘H. agni’ and ‘H. equigenitalis’, pathogenic in cattle, sheep and horses, respectively. [Book ref. 22, pp. 558–569.] haemoproteins See HAEM. Haemoproteus A genus of protozoa of the HAEMOSPORORINA. Species are parasitic in e.g. birds; the vectors are hippoboscid flies. haemorrhagic colitis COLITIS associated with bloody diarrhoea; when caused by EHEC it usually occurs without fever. haemorrhagic enteritis of turkeys An acute disease of turkeys (particularly turkey poults 6–12 weeks of age) caused by an AVIADENOVIRUS. Symptoms: depression, loss of appetite, bloody faeces; haemorrhages also occur in the muscles and internal organs. The disease may be fatal. [Book ref. 116, pp. 537–539.] (cf. MARBLE SPLEEN DISEASE.) haemorrhagic fever with renal syndrome See HANTAVIRUS. haemorrhagic fevers See VIRAL HAEMORRHAGIC FEVERS. haemorrhagic nephrosonephritis Syn. KOREAN HAEMORRHAGIC FEVER. haemorrhagic septicaemia (1) (in fish) See INFECTIOUS DROPSY and EGTVED DISEASE. (2) (barbone) An acute, often fatal, septicaemic CATTLE DISEASE which appears to be a primary PASTEURELLOSIS caused by strains of Pasteurella multocida. Onset is sudden, with fever, profuse salivation, and petechial haemorrhages in submucosal tissues; death may occur within ca. 1 day. A carrier state occurs. A vaccine is available. haemorrhagic syndrome See TRICHOTHECENES. Haemosporina See HAEMOSPORORINA. Haemospororina A suborder of protozoa (order EUCOCCIDIORIDA) previously classified as the suborder Haemosporina (sic) of the order Eucoccida [JP (1964) 11 7–20] or Eucoccidiida [JP (1980) 27 37–58]. In this suborder the organisms lack a conoid, syzygy does not occur, and motile zygotes are formed (cf. ADELEORINA, EIMERIORINA); some species form pigment from host cell haemoglobin (cf. PIROPLASMASINA). The organisms are heteroxenous, the asexual phase taking place in a vertebrate host and the sexual phase occurring in a blood-sucking insect. Genera: e.g. HAEMOPROTEUS, LEUCOCYTOZOON, PLASMODIUM. haemotropic (haematotropic; hemotropic; hematotropic) Having an affinity for the blood. (Used e.g. of blood parasites such as Plasmodium.) haemozoin (malarial pigment) A brown or black pigment which occurs in the intraerythrocytic schizont of Plasmodium spp (see PLASMODIUM and MALARIA). Haemozoin derives from the erythrocyte’s haemoglobin; the parasite ingests haemoglobin, uses the protein part, and (normally) detoxifies the remaining ferriprotoporphyrin IX (FP) by polymerizing it to haemozoin. (Unless detoxified by polymerization, FP can lyse the parasite’s membranes.) Haemozoin remains behind in the parasitized erythrocyte following release of merozoites.

Quinoline-type antimalarial agents (see AMINOQUINOLINES, appear to act by blocking the parasite’s ‘haem polymerase’ activity, thus killing the parasite by inhibiting detoxification of FP [Acta Tropica (1994) 56 157–171]. In order to facilitate studies on (i) the mechanism by which Plasmodium detoxifies FP, and (ii) the mode of action of quinoline-type antimalarials, the crystal structure has been determined for a synthetic compound, b-haematin, which is chemically identical to haemozoin [Nature (2000) 404 307–310]. Hafnia A genus of (usually non-capsulated) Gram-negative bacteria of the ENTEROBACTERIACEAE (q.v.). Most strains are motile at 25–30° C, but many are non-motile at 35° C. MR and VP reactions are variable at 35–37° C but MR −ve, VP +ve at 22–25° C. Lactose −ve (but Lac plasmids may occur); lysine and ornithine decarboxylases +ve; arginine dihydrolase −ve. Growth occurs e.g. on DCA and in KCN media. One species: H. alvei (formerly e.g. Enterobacter alvei or E. hafniae); many biotypes. H. alvei occurs in man, animals and birds, and in soil, sewage and water. H. alvei has been associated with diarrhoeal disease [JCM (1994) 32 2335–2337]; strains of H. alvei can produce A/E lesions (see entry EPEC). H. alvei has also been associated with liver abscesses, septicaemia, peritonitis and pneumonia [characterization of H. alvei isolates from human clinical extra-intestinal specimens: JMM (2001) 50 208–214]. (cf. KOSERELLA and OBESUMBACTERIUM.) hag gene In enterobacteria: the structural gene for FLAGELLIN. HAI test HAEMAGGLUTINATION-INHIBITION TEST. haidai See LAMINARIA. hair cell A narrow, elongated, apparently non-pigmented cell present at the ends of trichomes in certain filamentous CYANOBACTERIA. In ‘rivularian’ species (e.g. GLOEOTRICHIA), at least, hair cells seem to be formed under conditions of phosphorus or fixed nitrogen limitation; their function, if any, is unknown. hairpin In a single strand of DNA or RNA: a double-stranded region formed by base-pairing between sequences in the strand which are complementary and opposite in polarity (e.g., 5′ . . . GGCATG. . . . CATGCC . . . 3′ ). (cf. CRUCIFORM; see also STEMAND-LOOP STRUCTURE.) hairy-cell leukaemia (1) A T cell LEUKAEMIA (see HTLV-II in HTLV). (2) A B cell leukaemia. Both diseases are rare, and in each the cells have fine, hair-like projections. hairy leukoplakia (oral hairy leukoplakia) In e.g. HIV-infected individuals: whitish areas, typically found on the sides of the tongue, associated with replication of the EPSTEIN–BARR VIRUS; it may resemble oral candidiasis but, unlike candidiasis, it cannot be removed. A high proportion of patients with hairy leukoplakia subsequently develop AIDS. Hairy leukoplakia has been treated with e.g. high-dose ACYCLOVIR but it tends to recur on cessation of treatment. [Opportunistic oral infections in patients infected with HIV-1: RMM (1996) 7 151–163 (hairy leukoplakia: 157–158).] hairy root A disease which can affect various dicotyledonous plants; it is characterized by the proliferation of adventitious roots from the site of a wound infected with Agrobacterium rhizogenes (see AGROBACTERIUM). Pathogenesis appears to be analogous to that in CROWN GALL, involving the transfer, integration, and expression in plant host cells of a segment of an Ri (root-inducing) plasmid. (Ri and Ti plasmids belong to different incompatibility groups.) Conjugal transfer of Ri plasmids appears to occur constitutively at rather high frequencies, and induction of conjugal transfer by opines or other compounds has not been observed. Two types of Ri plasmid are known: the agropine type and the mannopine type; some of the catabolic QUININE)

354

Halomonas functions of the agropine strains are carried not by the Ri plasmid but by another plasmid which can cointegrate with it [MGG (1983) 190 204–214]. [Book ref. 55, pp. 271–286.] hairy shaker disease Syn. BORDER DISEASE. halazone See CHLORINE. half-a-Gram stain A non-specific staining procedure used e.g. for detecting cells of Legionella in smears of sputum or aspirates etc. The slide is flooded for 0.5–1 min with a solution of crystal violet, drained, and flooded with Gram’s iodine solution for 1–2 min. The slide is then rinsed well in tap-water and dried in air. (cf. GRAM STAIN.) half-chiasma See RECOMBINATION. half-reduction potential See REDOX POTENTIAL. Halicystis See DERBESIA. Halidrys See PHAEOPHYTA. Halimeda A genus of siphonaceous, mainly tropical or subtropical green seaweeds (division CHLOROPHYTA). The thallus is segmented and calcified, and contains both chloroplasts and amyloplasts. The cell wall contains a xylan (see XYLANS) as the main structural component, and is more or less heavily calcified with aragonite. When mature, the entire thallus is converted to gametangia, after which it dies. Related holocarpic, usually calcified algae include species of CAULERPA, PENICILLUS and UDOTEA. Haliscomenobacter A genus of Gram-negative, rod-shaped bacteria which occur e.g. in activated sludge. Individual cells are apparently non-motile; they commonly occur in sheathed trichomes. The organisms can utilize a range of carbon and nitrogen sources; PHB is not formed. H. hydrossis has a GC% of ca. 49. [Book ref. 45, pp. 425–440 (436–439).] hallucinogenic mushrooms Certain agarics whose fruiting bodies contain hallucinogenic compounds; they include certain species of Conocybe, Psilocybe (e.g. P. mexicana, P. semilanceata) and Stropharia. At least some of these fungi contain psilocybin and/or psilocin, hallucinogenic tryptamine derivatives related to serotonin. Some species of Lycoperdon also contain hallucinogenic substance(s). halo blight A typically seed-borne disease of beans (Phaseolus) caused by Pseudomonas phaseolicola. Small, translucent lesions on leaves later darken, each becoming surrounded by a yellowish ‘halo’; leaves later exhibit interveinal yellowing, and brownish spots may develop on pods. halo spot A CEREAL DISEASE, caused by Selenophoma donacis (Septoria oxyspora) which can affect e.g. barley, wheat and rye. Small, pale lesions, each with a purplish-brown margin, occur mainly on the leaves, and rows of dark-coloured pycnidia develop in line with the veins. (Halo spot is called ‘eyespot’ in some parts of the world: cf. EYESPOT sense 2.) halobacteria (1) Strains or species of Halobacterium. (2) Members of the family Halobacteriaceae. Halobacteriaceae A family of extremely halophilic archaeans which occur e.g. in salt lakes, evaporated brines, and salted fish (in which they can cause spoilage). Cells: rods, cocci or discs, containing orange, red or mauve carotenoid pigments (predominantly bacterioruberins). Division occurs by binary fission. The Gram reaction is negative. (See also CELL WALL, GAS VACUOLE and S LAYER.) Growth requires a minimum concentration of 1.5 M NaCl, good growth typically needing 3–4 M NaCl; cells accumulate electrolyte (mainly KCl) to an intracellular concentration at least equivalent to that in the environment. High concentrations of electrolyte are required to maintain the structural integrity of e.g. the cytoplasmic membrane and the ribosomes; in dilute solutions

some species lyse (owing to weakening of the cell envelope rather than to an osmotic effect per se). The organisms are chemoorganotrophs which use amino acids and/or carbohydrates as principal sources of carbon, and which typically grow aerobically; metabolism is respiratory (oxidative). The organisms form menaquinones rather than ubiquinones. Under microaerobic or anaerobic conditions some strains can use light energy (see PURPLE MEMBRANE; see also PHOTOTAXIS). Two genera: HALOBACTERIUM (the type genus) and HALOCOCCUS. Halobacterium A genus of catalase-positive, oxidase-positive archaeans of the HALOBACTERIACEAE. The cells are lophotrichously flagellated (or non-motile) frequently pleomorphic rods or filaments, or discs; they often contain gas vacuoles (which are plasmid-encoded in at least some strains), and they lyse in dilute solutions (e.g. NaCl ∼ca. 0.8–1.5 M). Binary fission occurs by constriction. Most strains can be cultured in e.g. well-aerated tryptone – yeast extract – salt media. Optimum growth temperature: 40–50° C. Some strains form a PURPLE MEMBRANE under microaerobic or anaerobic conditions. The DNA in Halobacterium spp is often composed of a major component (ca. 60–90% of the total DNA) with a GC% of ca. 66–68, and a minor component (‘satellite DNA’ or plasmid DNA) with a GC% of ca. 57–60. Type species: H. salinarium. H. halobium. See H. salinarium. H. pharaonis. Motile, alkalophilic (optimum pH: 8.5) rods which do not use sugars; substrates include e.g. formate, fumarate, pyruvate. Growth occurs optimally in 3.5 M NaCl. H. saccharovorum. Motile rods which form acid (mainly acetic acid) from sugars. Growth occurs optimally in 3.5–4.5 M NaCl. H. salinarium (= H. halobium). Motile, typically rod-shaped cells which grow aerobically or (strains with a purple membrane) anaerobically in the light. Amino acids are used for carbon and energy, although growth may be stimulated by carbohydrates (without acid formation). Growth occurs optimally in 4–5 M NaCl. H. vallismortis. Motile, very pleomorphic rods which use sugars, often with the formation of acid. Facultatively anaerobic. Growth occurs optimally in 4.3 M NaCl. H. volcanii. Mainly discoid or cup-shaped cells which are (apparently) non-flagellated but which are sometimes capable of a rotatory movement. Sugars are used for carbon and energy. Growth occurs optimally in 1.5–2.5 M NaCl. halocarbon See FREON. halocins See BACTERIOCINS. Halococcus A genus of catalase-positive and oxidase-positive archaeans of the HALOBACTERIACEAE. The cells are non-motile, orange- or red-pigmented cocci (diameter ca. 0.8–1.5 µm) which occur in pairs or in regular or irregular groups. At least 2.5 M NaCl is needed for growth; growth occurs optimally in 3.5–4.5 M NaCl. The organisms are much more resistant than are Halobacterium spp to hypotonic solutions. Amino acids are used for carbon and energy. Optimum growth temperature: 30–37° C. GC%: ca. 61–66. Type species: H. morrhuae [Book ref. 22, pp. 266–267]. halofantrine See MALARIA. halogens (as antimicrobial compounds) See entries CHLORINE, FLUORIDES, IODINE. Halomonas A genus (incertae sedis) of aerobic, facultatively anaerobic, chemoorganotrophic, halotolerant, Gram-negative 355

halonitrosoureas bacteria which occur e.g. in salterns and (presumably) in salt lakes etc. Cells: non-pigmented or yellow-pigmented, polarly or laterally flagellated rods, 0.6–0.8 × 1.6–1.9 µm, sometimes pleomorphic or filamentous. Metabolism may be respiratory (oxidative), with O2 or nitrate (anaerobic respiration) as terminal electron acceptor, or fermentative; anaerobic growth, without nitrate, can occur with glucose but not with other carbohydrates. Carbon sources include a wide range of alcohols, amino acids, organic acids and sugars. Salt (NaCl) tolerance: 0.1–32.5% w/v. Catalase +ve. Oxidase +ve. GC%: ca. 60. Type species: H. elongata. [Book ref. 22, pp. 340–343.] halonitrosoureas See N-NITROSO COMPOUNDS. halo-opsin See OPSIN. halophile An organism which grows optimally only in the presence of electrolyte (commonly NaCl) at concentrations above ca. 0.2 M, and which typically grows poorly, or not at all, in low concentrations of electrolyte; examples include e.g. species of ACTINOPOLYSPORA, DACTYLOCOCCOPSIS, HALOBACTERIUM, HALOCOCCUS, PARACOCCUS and VIBRIO. (cf. HALOTOLERANT.) A number of authors have accepted the following categories: slightly halophilic (optimum growth in the presence of 0.2–0.5 M electrolyte); moderately halophilic (optimum growth in 0.5–2.5 M electrolyte); extremely halophilic (optimum growth in >2.5 M electrolyte). [Halophilic and halotolerant organisms: Book ref. 157, pp. 171–214, and Book ref. 191, pp. 55–81.] Halopteris See PHAEOPHYTA. halorhodopsin A RETINAL-containing protein pigment (MWt ca. 25000) which occurs in the PURPLE MEMBRANE of Halobacterium salinarium and which is involved in transmembrane ion translocation. Maximum absorption appears to occur at ca. 580 nm, the absorption characteristics being stabilized by anions (primarily Cl− ). On illumination, halorhodopsin undergoes cyclical changes in its absorption characteristics with a periodicity of ca. 5–10 msec; several photointermediates appear to be involved. Halorhodopsin undergoes bleaching when illuminated in the presence of hydroxylamine. Some strains of Halobacterium salinarium (e.g. JW-5, W-296), which cannot synthesize retinal, produce bacterio-opsin but are repressed in the synthesis of haloopsin. Halothrix See PHAEOPHYTA. halotolerant Refers to the ability of a non-HALOPHILE to grow in the presence of high concentrations of electrolyte (e.g. up to ca. 2.5 M); examples of halotolerant organisms include e.g. HALOMONAS and strains of Staphylococcus. Halteria A genus of freshwater ciliates (order OLIGOTRICHIDA). Cells: roughly spherical, with very conspicuous oral ciliature and a number of groups of ‘cirri’ or ‘bristles’ forming an equatorial band. H. grandinella is ca. 25–50 µm in diam., has a ‘bouncing’ type of movement, and occurs e.g. in ponds and organically polluted waters (see SAPROBITY SYSTEM) where it feeds on bacteria; the organism is fairly tolerant of low O2 levels, but is sensitive to NH3 and H2 S. ham See CURING (1); MEAT SPOILAGE; SOFT CORE HAM. hamanatto (black beans) An oriental food made by fermenting whole soybeans with strains of Aspergillus oryzae. Beans are steamed, coated with wheat flour, inoculated with A. oryzae, and incubated 1–2 days. Brine and spices are added and incubation is continued 6–12 months; the beans are then dried. hamathecium A term which refers, collectively, to the various types of structure which may occur between and around the asci in an ascocarp: see e.g. PARAPHYSIS, PARAPHYSOID, PSEUDOPARAPHYSIS and PERIPHYSES.

Hamigera See TALAROMYCES. Hammondia hammondi Syn. Isospora datusi. hamycin A heptaene POLYENE ANTIBIOTIC produced by Streptomyces pimprina; it is effective against only a limited range of fungi, but is particularly effective against Candida albicans. hand, foot and mouth disease An acute, highly infectious, self-limiting disease (mainly of children) characterized by the development of vesicular-ulcerative lesions in the mouth with similar lesions scattered on the soles of the feet and on the palms of the hands. The causal agent is usually coxsackievirus A16, but A4, A5, A9, A10, B2 and B5 have also been implicated. (cf. FOOT AND MOUTH DISEASE.) hanging drop A direct, visual procedure used for determining the MOTILITY of microorganisms in a fluid medium. A COVERGLASS is placed flat on the bench, and a drop of fluid (e.g. from a broth CULTURE) is transferred (e.g. by a LOOP) from the culture to the centre of the cover-glass. A plasticine ring (diam. ca. 1.5 cm, ca. 4 mm thick) is gently pressed onto one face of a SLIDE; the ring (attached to the slide) is then gently pressed onto the cover-glass so that the ring becomes sandwiched between the (parallel) faces of slide and cover-glass. The whole is then inverted, so that the drop hangs freely beneath the cover-glass, and can be examined under the microscope. This method avoids microcurrents which could give a false impression of motility. Hanks’ BSS Hanks’ BALANCED SALT SOLUTION; it contains (g/l): NaCl (8.0), KCl (0.4), CaCl2 .2H2 O (0.185), MgSO4 .7H2 O (0.1), MgCl2 .6H2 O (0.1), Na2 HPO4 .H2 O (0.06), KH2 PO4 (0.06), NaHCO3 (0.35), glucose (1.0), and phenol red (0.01); pH: 7.0–7.2. Hanseniaspora A genus of fungi (family SACCHAROMYCETACEAE). The genus contains the teleomorphs of KLOECKERA spp. Ascospores may be bowler-hat-shaped, 1–4 per ascus, and released at maturity, or they may be spherical, with or without an equatorial ridge, smooth or warty, and not released at maturity. [Book ref. 100, pp. 154–164.] Hansen’s bacillus Mycobacterium leprae. Hansen’s disease Syn. LEPROSY. Hansenula A genus of yeasts (family SACCHAROMYCETACEAE) in which the cells are generally spheroidal, ellipsoidal or elongate; vegetative reproduction occurs by multilateral budding. Pseudomycelium or true mycelium may be formed. Asci are generally dehiscent, occasionally persistent. Ascospores: hemispheroidal, Saturn-shaped, or bowler-hat-shaped. Species may be homothallic or heterothallic. Most species can ferment glucose, some can also ferment other sugars, and some (e.g. H. canadensis) are non-fermentative. NO3 − is assimilated. Thirty species are recognized, including e.g. H. anomala (anamorph: Candida pelliculosa), H. canadensis (conspecific with H. wingei ), H. capsulata, H. jadinii (anamorph: Candida utilis), H. polymorpha (see also METHYLOTROPHY), H. wickerhamii. Species have been isolated from tree exudates, soil, insect larvae and frass, etc. [Book ref. 100, pp. 165–213.] Hantaan virus See HANTAVIRUS. Hantavirus A genus of viruses of the family BUNYAVIRIDAE [taxonomic proposal: Virol. (1983) 131 482–491]. The enveloped, spherical virions each contain a negative-sense ssRNA genome consisting of three fragments. Approximately half of the >20 known species are associated with human disease – either (i) the hantavirus pulmonary syndrome (HPS), or (ii) haemorrhagic fever with renal syndrome (HFRS). Unlike other members of the Bunyaviridae (which are maintained in arthropods) hantaviruses are found in populations of 356

HBB Haptophyceae Syn. PRYMNESIOPHYCEAE. hard cider (American) Syn. CIDER. hard gill See WATERY STIPE. hard-pad A form of CANINE DISTEMPER which begins with tenderness and keratinization of the feet, usually followed by CNS involvement and death. hard swell See SWELL. hare fibroma virus See LEPORIPOXVIRUS. Harpellales See TRICHOMYCETES. harpin (plant. pathol.) Any of certain types of glycine-rich protein, encoded by plant-pathogenic bacteria, which (at least in culture) can be secreted via a type III PROTEIN SECRETION system and which are able to elicit a heat-stable HYPERSENSITIVITY reaction in the leaves of tobacco and certain other plants [see e.g. JB (1997) 179 5655–5662]. (See also AVIRULENCE GENE.) Harpochytriales See CHYTRIDIOMYCETES. Harposporium See HYPHOMYCETES and NEMATOPHAGOUS FUNGI. Hartig net See MYCORRHIZA. Hartmannella A genus of amoebae which are similar to ACANTHAMOEBA spp except that they do not produce acanthopodia from the (usually well-defined) hyaline cap of the pseudopodium. Hartmannula See HYPOSTOMATIA. hartrot (bronze leaf wilt; Coronie wilt) A disease of the coconut palm (Cocos nucifera) caused by a species of PHYTOMONAS which invades the phloem. Symptoms: yellowing and falling of leaves and blackening of inflorescences; unripe, internally blackened coconuts fall prematurely. Trees may die within three months of the initial signs. hart’s truffle See TRUFFLES. Harvey murine sarcoma virus (Ha-MSV) A replication-defective, v-onc+ , fibroblast-transforming MURINE SARCOMA VIRUS which was isolated from BALB/c mice inoculated neonatally with rat-passaged MOLONEY MURINE LEUKAEMIA VIRUS (MoMuLV). Ha-MSV carries the oncogene v-ras (v-Ha-ras) and apparently arose by recombination between Mo-MuLV and a rat cellular ras sequence (Ha-ras: see RAS). Infection of newborn rodents with Ha-MSV results in anaemia, splenomegaly (resulting from proliferation of erythroblasts) and erythroleukaemia, as well as sarcomas. (cf. KIRSTEN MURINE SARCOMA VIRUS.) HAT medium See HYBRIDOMA. haustorium A specialized hyphal structure formed e.g. by certain plant-parasitic fungi (e.g. Erysiphe, Peronospora) in order to obtain nutrients from the host plant; it develops within a host cell after a small hyphal branch has penetrated the host cell wall, but it remains external to the host cell’s cytoplasmic membrane. A haustorium may be spherical, club-shaped or elongated (branched or unbranched) according to the species of fungus which forms it. (Haustoria are also formed by the mycobionts of certain lichens.) Haverhill fever See RAT-BITE FEVER. Hawii virus See SMALL ROUND STRUCTURED VIRUSES. hay fever See TYPE I REACTION. Hayflick medium A medium used for the culture of Mycoplasma. spp. It consists of heart infusion broth supplemented with membrane-filtered horse serum (which provides sterols), fresh yeast extract solution, calf thymus DNA solution, thallium acetate and benzylpenicillin; the pH is adjusted to 6.8–7.8 according to strain. The solid medium is made by using a purified agar (e.g. Noble agar) as gelling agent. HBB (2-(a-hydroxybenzyl)-benzimidazole) An ANTIVIRAL AGENT which selectively inhibits the replication of a number of picornaviruses in cell cultures; it inhibits the initiation of viral

(persistently infected) rodents – including rats (Seoul virus), mice (Sin Nombre virus, Dobrava-Belgrade virus, Hantaan virus) and voles (Puumala virus); human infection appears to occur mainly by inhalation of aerosols of the infected urine, faeces etc. of rodents. Species of Hantavirus include: Hantaan virus (HFRS; see also KOREAN HAEMORRHAGIC FEVER), Seoul virus (HFRS), Puumala virus (HFRS), Dobrava-Belgrade virus (HFRS), Sin Nombre virus (HPS), Andes virus (HPS), Black Creek Canal Virus (HPS) and Laguna Negra virus (HPS). [Hantaviruses (persistence in rodent reservoirs): TIM (2000) 8 61–67. Hantaviruses (review): JMM (2000) 49 587–599.] Haploangium See MYXOBACTERALES. haploid Having a PLOIDY of one. (cf. DIPLOID, POLYPLOID.) haploidization (mycol.) See PARASEXUAL PROCESSES. haplokinety (1) The infraciliary base (only) of a stichodyad PARORAL MEMBRANE. (2) A stichodyad paroral membrane. haplomycosis Syn. ADIASPIROMYCOSIS. haplont (1) (noun) An organism in whose life cycle only the zygote is diploid. (cf. DIPLONT.) (2) The haploid form of an organism, e.g. a gametophyte (see ALTERNATION OF GENERATIONS). (3) (haplontic) (adj.) Refers to either (1) or (2) above. haplophase In organisms which reproduce sexually: the haploid phase of the life cycle. In many higher fungi haplophase and DIPLOPHASE are separated by DIKARYOPHASE. Haplospora See PHAEOPHYTA. Haplosporangium See ADIASPIROMYCOSIS. Haplosporidium A genus of protozoa (class STELLATOSPOREA) which are parasitic in various aquatic invertebrates (including annelids and molluscs). The spores are operculate and characteristically bear filamentous extensions which arise from the outer spore coat and are typically coiled around the spore. [Spore ultrastructure in H. lusitanicum: J. Parasitol. (1984) 70 358–371.] The vegetative stage is plasmodial. haplosporosomes See STELLATOSPOREA. hapten A substance which can elicit an immune response only when combined with another molecule or particle (carrier ); if administered on its own it fails e.g. to stimulate antibody production (but cf. autocoupling hapten, below). The free hapten can, however, combine with antibodies raised against the hapten–carrier complex; such combination may or may not result in the precipitation of the hapten–antibody complex. A substance which acts as a hapten in one species may act as a complete antigen in another – e.g. the pneumococcal capsular polysaccharides are haptenic in the rabbit but antigenic in man. A hapten may be artificially bound to a protein in order to increase the immunological specificity of that protein. Autocoupling haptens bind spontaneously to tissue carriers in vivo, thus becoming antigenic. (See also ALLERGEN.) hapteron See CYATHUS. haptocyst An EXTRUSOME in the tentacles of suctorian ciliates. haptonema A thread-like appendage present on unicellular algae of the PRYMNESIOPHYCEAE. Structurally, a haptonema bears some resemblance to a eukaryotic FLAGELLUM but contains fewer microtubules (which are arranged differently from those in a flagellum) and has a sheath composed of several concentric membranes, the innermost enclosing the microtubules. Haptonemata range from relatively short (e.g. in Prymnesium parvum) to very long (>80 µm in Chrysochromulina spp); most haptonemata (but not that of Prymnesium) can coil and uncoil: e.g., in Chrysochromulina spp the haptonema remains coiled while the organism is swimming and becomes extended when the cell comes to rest. The haptonema is believed to function as an attachment organelle. 357

HBcAg GroES, GroEL and DnaK seem to prevent misfolding or aggregation of unfolded proteins, while the Lon protease degrades abnormal proteins. The heat-shock genes constitute a REGULON composed of several unlinked operons (for example: promoter–dnaK –dnaJ and promoter–groES –groEL). The heat-shock regulon is under the control of a positive transcriptional activator encoded by gene rpoH (previously called htpR). RpoH (MWt ca. 32000) is a SIGMA FACTOR (s32 ) which interacts with RNA POLYMERASE, producing a holoenzyme (Es32 ) that promotes transcription from heat-shock promoters more efficiently than does Es70 . (Transcription of the rpoH gene itself requires Es70 [JB (1986) 166 380–384].) Following heat shock, the increased levels of RpoH are due mainly to increased translation of the protein – rather to increased transcription of rpoH. The heat-induced translation from rpoH mRNA involves an effect of temperature on a secondary structure formed in the mRNA by base-pairing between a site immediately downstream of the start codon (a downstream box ) and another region in the coding sequence. This secondary structure normally inhibits translation, but on temperature upshift it is destabilized so that translation can occur; thus, the mRNA acts as a thermosensor (an RNA thermometer ) for expression of s32 [GD (1999) 13 633–636]. Although synthesized under normal conditions, s32 has a short half-life (about 1 min); it appears that, within the cell, s32 forms complexes with DnaK, DnaJ and GrpE and is subsequently degraded by the FtsH protease. During heat shock DnaK binds preferentially to denatured proteins – leaving RpoH free to function as a sigma factor [EMBO (1996) 15 607–617]. The heat-shock response in other bacteria. In some bacteria the mechanism for regulating the heat-shock response differs from that in E. coli. In some cases there is a regulatory sequence upstream of heat-shock genes; this inverted repeat sequence, termed CIRCE (controlling inverted repeat of chaperone expression), occurs e.g. in strains of Bacillus and Clostridium and is also found in some Gram-negative bacteria. In Bradyrhizobium japonicum the control mechanism includes at least two distinct regulatory systems involving CIRCE and a s32 -like sigma factor [JB (1996) 178 5337–5346]. More recently it has been reported that control of the heatshock response involves negative regulation by repressor proteins (in conjunction with cis-acting DNA sequences) which inhibit transcription of the HSP genes under normal physiological conditions [Mol. Microbiol. (1999) 31 1–8]. (See also SOS SYSTEM.) Strains of E. coli mutant in the rpoH gene have been useful in the OVERPRODUCTION of recombinant proteins. heated lid cycler See THERMOCYCLER. heavy chain A class-specific polypeptide IMMUNOGLOBULIN component (MWt ca. 50000–70000, depending on Ig class). The various types of heavy chain are designated alpha, gamma, delta, epsilon and mu – corresponding to Ig classes IgA, IgG, IgD, IgE and IgM, respectively. In IgM, different C-terminal sequences occur in the heavy chains of the membrane-associated and pentameric forms. Certain Ig classes can be divided into subclasses on the basis of minor differences in their heavy chains. heavy metals (and their compounds) (as antimicrobial agents) Although trace amounts of certain heavy metal ions are essential for the growth of microorganisms, higher concentrations may exhibit antimicrobial activity. Heavy metal ions bind to certain groups (particularly thiol groups) and appear to exert antimicrobial activity largely by inactivating proteins, nucleic acids and

RNA synthesis. HBB-resistant mutants emerge rapidly; HBBdependent mutants have also been isolated. HBcAg See HEPATITIS B VIRUS and HEPATITIS B. HBeAg See HEPATITIS B VIRUS and HEPATITIS B. HBsAg See HEPATITIS B VIRUS and HEPATITIS B. HBV HEPATITIS B VIRUS. HCAM Syn. CD44. HCC HEPATOCELLULAR CARCINOMA. HCMV Human cytomegalovirus: see BETAHERPESVIRINAE. HCV HEPATITIS C VIRUS. HCVs (human caliciviruses) See SMALL ROUND STRUCTURED VIRUSES. HD protein Helix-destabilizing protein (see SINGLE-STRAND BINDING PROTEIN). HD50 (CH50 ; C′ H50 ) Haemolytic dose (50%): the quantity of COMPLEMENT needed to lyse 50% of a standardized suspension of sensitized erythrocytes. In a COMPLEMENT-FIXATION TEST the HD50 may be used as the unit in place of MHD (q.v.); this gives a more accurate end-point (since the graph ‘%lysis of cells versus quantity of complement’ is sigmoidal). HDAg See DELTA VIRUS. HDCV Human diploid cell vaccine (see RABIES). hDNA Hybrid DNA. (See e.g. CLONING.) H-DNA See TRIPLEX DNA. HE-cellulose (HEC) Hydroxyethylcellulose: a neutral cellulose derivative sometimes used in preference to CM-CELLULOSE in CELLULASE assays. HE markers See TRANSFORMATION (1). headful mechanism A mechanism of genome packaging during virion assembly: packaging is initiated by insertion into a prohead (or provirion) of one end of a concatemeric form of the genome (which, at or before insertion, may be cut at a particular sequence); incorporation of the genome then continues until the head is full. Thus, termination of packaging is determined only by the length of the nucleic acid packaged, and not by a specific sequence in the nucleic acid. (See e.g. BACTERIOPHAGE MU and BACTERIOPHAGE P22; cf. e.g. BACTERIOPHAGE l.) Heaf test A form of TUBERCULIN TEST. PPD is spread over a small area of skin and is then pressed into the skin with a ‘Heaf gun’: an instrument which punctures the skin with several small needles. heart rot See TREE DISEASES. heartwater See COWDRIA. heat-fixed smear See FIXATION. heat-shock proteins (HSPs) Proteins which are synthesized at greatly (but transiently) increased levels in an organism in response to a sudden rise in temperature or to certain other types of stress (e.g. ultraviolet radiation, virus infection, ethanol, or the intracellular accumulation of abnormal proteins); HSPs may be necessary for survival of the organism at higher temperatures, and they are produced at the expense of ‘normal’ proteins. Such a heat-shock response has been observed in a wide range of species – from bacteria and yeasts to plants and animals; at least some HSPs have been highly conserved through evolution, but the response is regulated differently in different organisms. In Escherichia coli there are at least 17 HSPs which include the products of genes dnaJ, dnaK, groEL, groES, rpoD, lysU and lon. Synthesis of these proteins reaches a peak ca. 5–10 min after a rise in temperature (for example, 30 → 42° C), and subsequently declines to a new steady state which is greater than that at the lower temperature. Some HSPs apparently cope with stress-induced damage – for example, the molecular chaperones 358

Helicobacter Helicases I and III both act processively and move in the 5′ -to3′ direction along the strand to which they are bound. Helicase I is encoded by the traI gene of the F plasmid [PNAS (1983) 80 4659–4663]; it seems to be responsible for nicking at oriT in the F plasmid [JBC (1991) 266 16232–16237], and may be involved in unwinding the plasmid DNA for transfer during CONJUGATION (sense 1b). Helicase III cannot replace either the Rep protein or helicase II. Some bacteriophages encode their own helicases; for example, the dda gene product of phage T4 is a helicase, while the gp4 of phage T7 is a protein with both helicase and PRIMASE activities. The DnaB helicase, which is active e.g. in DNA replication, is a ring-shaped hexamer of DnaB proteins [see e.g. Cell (1996) 86 177–180]. Helicobacter A genus of asporogenous Gram-negative bacteria classified within the e (epsilon) subdivision (= rRNA superfamily VI) of the taxon Proteobacteria (which also includes the family CAMPYLOBACTERACEAE). The cells are typically curved/helical rods with one or more sheathed flagella (unsheathed e.g. in H. pullorum). Currently there are ∼20 named species, many of which have been isolated from the intestines (and often liver) of animals (e.g. dogs, sheep, pigs, rodents, chickens). However, attention has been focused primarily on the species H. pylori owing to its association with e.g. gastritis and peptic-ulcer disease in humans. H. pylori was formerly classified within the genus Campylobacter, but was re-classified [IJSB (1989) 39 397–405]. Cells: curved/helical, ca. 0.5–0.9 µm wide and up to ∼3 µm in length; motile (several flagella). Genome: circular, approx. 1700 kb; GC%: average 39, but significant differences occur in specific regions – one such region including the cag PATHOGENICITY ISLAND [H. pylori strain 26695 (complete genome): Nature (1997) 388 539–547]. Chemoorganoheterotrophic. Microaerophilic. Culture on enriched media (e.g. blood, chocolate agar) needs high humidity (freshly poured, undried plates) and a gaseous phase of e.g. oxygen/carbon dioxide/nitrogen (5%/10%/85%); grey, translucent colonies (60–70 minutes [Microbiology (2003) 149 1001–1010]. Reproduced from Bacteria, 5th edition, Figure 3.2, pages 44–45, Paul Singleton (1999) copyright John Wiley & Sons Ltd, UK (ISBN 0471-98880-4) with permission from the publisher.

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hepatitis B virus Lab. diagnosis involves detection of HBV antigens in the serum. HBsAg (see HEPATITIS B VIRUS) appears in the serum during the incubation period and persists through the symptomatic phase of the disease. It usually begins to disappear ca. 2–3 months after the onset of symptoms; if it persists for >6 months, the patient has become a carrier and may develop chronic liver disease. Anti-HBsAg antibodies appear only late in convalescence; the high levels of HBsAg present in the blood may induce immune tolerance to this antigen. HBeAg appears in the serum just before symptoms begin; its appearance is associated with high infectivity and the presence of whole (infectious) virions (‘Dane particles’) in the blood. HBcAg does not appear in the serum, but anti-HBcAg antibodies can be detected as symptoms begin. Anti-HBcAg IgM antibodies disappear late in the convalescence phase, but anti-HBcAg IgG antibodies may persist for years (possibly for life), and detection of the latter is a useful indicator of previous infection. [Screening blood samples for HBV by PCR: Lancet (1999) 353 359–363.] Treatment. There is no specific treatment for the clinical disease. Antiserum may be used for pre- or post-exposure prophylaxis. Vaccines containing HBsAg are available [PM (1984) 75 199–211]. hepatitis B virus (HBV) A virus of the HEPADNAVIRIDAE (q.v.) which causes HEPATITIS B in man, and which is also apparently a causal agent of human hepatocellular carcinoma (HCC). (HBV can also infect chimpanzees, but does not cause chronic hepatitis or HCC in these animals.) (cf. WOODCHUCK HEPATITIS VIRUS.) On infection of a new host (see HEPATITIS B), the HBV virion attaches to the surface of a hepatocyte and penetrates the cell by endocytosis or by fusion of the viral envelope with the host cell plasma membrane. HBV surface (envelope) antigen (HBsAg) and core antigen (HBcAg) become associated with the plasma membrane of the infected cell, and subsequently large amounts of HBsAg are released into the circulation in the form of non-infectious (DNA-free), spherical or tubular lipoprotein particles (ca. 22 nm diam.). HBsAg (formerly known e.g. as ‘Australia antigen’, Au antigen, or hepatitis-associated antigen, HAA) is a dimer of two molecules, linked by disulphide bonds, of the envelope ‘major protein’ (see HEPADNAVIRIDAE). HBcAg is the major capsid polypeptide (P22C ). The soluble e antigen (HBeAg) is a product of proteolytic cleavage of HBcAg. The appearance in the serum of infected individuals of antibodies to these antigens provides a useful means of monitoring disease development (see HEPATITIS B). HBV strains can be serotyped on the basis of their HBsAg. HBsAg contains a group-specific determinant (designated a), common to all subtypes, together with subtype-specific determinants (designated d, y, w and r ); strains typically contain either d or y with either w or r. The four principal serotypes, which differ in geographical distribution, are adw, adr, ayw and ayr. The subtype determinants are useful epidemiological markers. In ca. 5–10% of individuals infected with HBV, HBsAg persists in the circulation for >6 months, and a carrier state is established which may persist for life. The carrier state may be asymptomatic (latent infection) or symptomatic (with e.g. chronic active hepatitis, cirrhosis, and/or HCC), and is most likely to develop in e.g. perinatally-infected or immunodeficient individuals. In HBV carriers, viral DNA may integrate at one or more (apparently random) sites in the host cell genome; the integrated sequences may be complete genomes or subgenomic fragments, and in HCC cells they are often extensively rearranged, with e.g. multiple deletions, inversions, duplications, etc. Rearrangements also occur in the flanking cellular sequences.

to the methods used for its isolation; that used as an ANTICOAGULANT (heparin inhibits thrombin activity) has a MWt of ca. 25000. In addition to anticoagulant activity, heparin can e.g. modify (limit) delayed hypersensitivity reactions in mice and guinea pigs (mechanism unknown), stimulate phagocytosis, inhibit the alternative pathway of complement fixation (by enhancing the activity of Factor H), and inhibit eosinophilmediated ADCC. Heparin is cleaved by heparinases, and its activity can be neutralized by e.g. protamines. hepatitis Inflammation of the liver. Hepatitis is often caused by viruses (e.g. HEPATITIS A, HEPATITIS B, HEPATITIS C); hepatitis D and hepatitis E viruses are less-common causal agents. The significance of infection with hepatitis G virus is currently uncertain [transfusion-associated hepatitis G virus infection: NEJM (1997) 336 747–754; RMM (1998) 9 207–215]. Hepatitis may also occur as a symptom of non-viral infectious diseases (see e.g. amoebic DYSENTERY). [Diagnostic perspective of viral hepatitis: RMM (1997) 8 197–207.] hepatitis A (infectious hepatitis; epidemic hepatitis; short-incubation hepatitis) A viral HEPATITIS caused by the hepatitis A virus (HAV, = ENTEROVIRUS type 72); it tends to occur in epidemics among children and young adults, particularly in closed institutions (e.g. mental hospitals). Man is probably the only natural host, but certain other primates (e.g. chimpanzees) can be infected. A carrier state is not known. Infection occurs mainly by consumption of water, milk or food contaminated with human faeces – e.g. shellfish harvested from sewage-polluted waters. HAV replicates in hepatocytes and is presumed to reach the intestine (and hence faeces) via the bile duct. The peak excretion of virus occurs during the latter half of the incubation period (2–6 weeks). Symptoms: fatigue, anorexia, low-grade fever, some abdominal pain, and sometimes jaundice. The disease is usually self-limiting within a few weeks; rarely, a severe, fulminant, often fatal hepatitis develops. Lab. diagnosis: demonstration of HAV in faeces; serological tests for anti-HAV IgM antibodies in serum. hepatitis B (serum hepatitis; homologous serum jaundice; longincubation hepatitis) A viral HEPATITIS caused by the HEPATITIS B VIRUS (HBV). Incubation period: 2–6 months (but occasionally as short as 2 weeks). Infection occurs by direct inoculation or by contamination of mucous membranes. The virus is present in the blood and body fluids (saliva, semen, mucus, wound exudates etc) of an infected person. Transmission may thus occur by the transfusion of blood or blood products from infected donors; by tattooing, ear-piercing, vaccination, renal dialysis, etc, using contaminated needles; by sexual contact; or (in infants) during birth. (Intrauterine infection is uncommon since HBV does not normally cross the placenta.) HBV reaches the liver via the blood and replicates in the hepatocytes. The disease may be mild or subclinical, and a carrier state is recognized (see HEPATITIS B VIRUS). In clinical cases, onset is gradual with jaundice and e.g. nausea, malaise, pains in muscles and joints, with or without fever; occasionally acute hepatic failure occurs. (See also DELTA VIRUS.) Pathogenesis appears to involve the host’s immune response to viral antigens in the plasma membranes of infected hepatocytes. The condition may be self-limiting, or chronic liver disease may develop; chronic infection is associated with an increased risk of hepatocellular carcinoma (HCC: see HEPATITIS B VIRUS) and possibly other tumours, including KAPOSI’S SARCOMA [JAMA (1984) 251 1007–1008]. HCC is a major cause of death in regions where HBV is endemic and neonatal infection is common (e.g. in regions of China and tropical Africa). 363

hepatitis C [Duplications of flanking cellular sequences and model for HBV DNA integration: PNAS (1985) 82 4458–4462.] Integrated viral DNA may continue to be expressed, resulting in the continued synthesis of e.g. HBsAg; however, in HCC cells virus replication and gene expression appear generally to be absent. Integrated HBV DNA has been found in the majority of HCC cells examined, and integration is generally assumed to precede carcinogenesis; however, the relationship between viral DNA integration and the induction of HCC is unknown. HCC generally does not develop for many years after the establishment of the carrier state; in at least some cases additional factors – such as genetic predisposition, immunological factors, or exposure to chemical co-carcinogens (e.g. AFLATOXINS) – may be involved. [Biology and epidemiology of HBV: Book ref. 110, pp. 43– 65; molecular biology of HBV: Nature (1985) 317 489–495.] hepatitis C A viral HEPATITIS caused by the HEPATITIS C VIRUS (HCV); most cases of hepatitis formerly referred to as NANB (non-A-non-B) hepatitis are now believed to have been hepatitis C. In nature, hepatitis C is limited to humans (chimpanzees can be infected experimentally). The route of transmission of HCV is commonly parenteral (including blood transfusion); sexual and perinatal transmission also occur. The incubation period (4–12 weeks) may be followed by nonspecific symptoms that resolve within weeks or months. Infection is often asymptomatic; jaundice is uncommon. HCV RNA is detectable in serum (e.g. by rtPCR) before seroconversion. In a high proportion of patients infection becomes chronic (indicated e.g. by the continuing presence of HCV RNA in serum); usually asymptomatic, the chronic disease may nevertheless give rise to e.g. hepatocellular carcinoma or cirrhosis in a proportion of cases after 20–30 years. (Preliminary data have suggested that there is a cerebral effect (altered cerebral metabolism) in patients chronically infected with HCV [Lancet (2001) 358 38–39].) Lab. diagnosis: e.g. screening (with a third-generation ELISA) for specific antibodies; antigens used in the assay consist of synthetic peptides/recombinant proteins representing products which are encoded by particular regions of the HCV genome. Any specimen positive in this assay is re-tested by a supplemental assay such as the recombinant immunoblot assay (RIBA). In a RIBA test, a nitrocellulose strip is coated with peptides/recombinant proteins similar to those used in the ELISA, each type of peptide and protein forming a separate band on the strip. The strip is exposed to a sample of serum (permitting antibody–antigen binding) and then to an anti-human IgG–enzyme conjugate. After washing, bound antibodies are detected by adding the enzyme’s substrate and examining the strip for the (coloured) product of hydrolysis; the presence of particular antibodies in the serum is deduced from the development of colour at particular band(s) on the strip. Nucleic-acid-based tests are useful for the early detection of HCV – and also for following the efficacy of antiviral therapy. [Quantification of hepatitis C virus by bDNA assay: JCM (1997) 35 187–192; rtPCR-based screening for HCV in a blood bank: Lancet (1999) 353 359–363.] hepatitis C virus (HCV) A small, enveloped, positive-sense ssRNA virus which causes HEPATITIS C in man. A population or sample of HCV from a given source exists as a QUASISPECIES. HCV has not been cultured. The 5′ non-coding end of the HCV genome is followed (5′ → 3′ ) by sequences which encode: core protein, envelope proteins, membrane-binding function, helicase and protease, membranebinding function, RNA polymerase and a 3′ non-coding region. One of the envelope protein genes includes a hypervariable region designated HVR-1.

Six major genotypes and >60 subtypes of HCV have been distinguished. Treatment of hepatitis C is apparently influenced by the specific genotype involved and the level of viraemia; disease caused by genotype 2 or 3, in conjunction with low-level viraemia, is reportedly more likely to respond in a sustained fashion to treatment with IFN-a, while disease caused by genotype 1 or 4 is apparently more refractory. [Quantification of HCV in plasma samples: JCM (1997) 35 187–192.] In many cases HCV causes persistent infection. Persistence may be facilitated by the relatively poor immunogenicity of the virus and the low-level viraemia. Changes in viral antigens, due e.g. to mutations in HVR-1, may also contribute to persistence; however, genetic drift in HCV may be independent of the host’s (weak) immune pressure [JV (2000) 74 2541–2549]. (See also CD81.) hepatitis D, E See HEPATITIS. hepatitis D virus Syn. DELTA VIRUS. hepatitis delta virus Syn. DELTA VIRUS. hepatitis G virus See HEPATITIS. hepatitis X Hepatitis in dogs caused by ingestion of food contaminated with AFLATOXINS; the liver becomes necrotic and congested, with haemorrhagic oedema of the gall bladder mucosa. hepatocellular carcinoma (HCC) A CARCINOMA of liver cells. Primary HCC can be caused e.g. by HEPATITIS B VIRUS and WOODCHUCK HEPATITIS VIRUS. (See also HEPATITIS C.) hepatotoxin A TOXIN which acts on the liver. hepatotropism See TROPISM (sense 2). HEPES A zwitterionic pH buffer: N-2-hydroxyethylpiperazineN ′ -2-ethanesulphonic acid. HEPES is widely used e.g. in TISSUE CULTURES, and has also been used in bacterial cultures; it is readily soluble in water, and does not bind divalent cations such as Ca2+ , Mg2+ or Cu2+ . At 37° C the pKa of HEPES is ca. 7.3; at 25° C it is ca. 7.5. (cf. BICINE.) Herbert’s pits See TRACHOMA. herbicolin A An acyl peptide antibiotic produced by Erwinia herbicola. It can inhibit the growth of yeasts and filamentous fungi, and can kill sterol-requiring mollicutes [JAC (1985) 16 449–455]; it is inactive against other bacteria. herbivorous Refers to protozoa which feed on bacteria and/or algae. (cf. CARNIVOROUS.) herd immunity See EPIDEMIOLOGY. herd structure See EPIDEMIOLOGY. Heribaudiella See PHAEOPHYTA. Hericium A genus of fungi of the APHYLLOPHORALES. hermaphroditism The phenomenon in which an individual has both male and female sexual organs; such an individual may exhibit HOMOTHALLISM or HETEROTHALLISM. herpangina An acute (usually self-limiting) infectious PHARYNGITIS, occurring mainly in children and young adults, caused by coxsackieviruses A2–A6, A8 and A10. Small, vesicular, ulcerating lesions develop in the pharyngeal region, and there may be varying degrees of fever and/or prostration. herpes (1) Any disease caused by a herpesvirus (especially HERPES SIMPLEX but also e.g. HERPES ZOSTER) and characterized by the formation of small vesicular lesions on skin and mucous membranes. (2) Used increasingly as a synonym of genital herpes (see HERPES SIMPLEX). herpes genitalis See HERPES SIMPLEX. herpes gladiatorum See HERPES SIMPLEX. herpes labialis See HERPES SIMPLEX. herpes simplex An infectious disease, caused by herpes simplex virus (HSV) type 1 or 2 (see ALPHAHERPESVIRINAE), which 364

herpes zoster (typically) involves the formation of thin-walled vesicles that ulcerate, crust and heal; vesicles occur, often in clusters, on skin and/or mucous membranes. Transmission occurs mainly by person-to-person contact – e.g. sexual contact, kissing, contact sports such as wrestling (‘herpes gladiatorum’). Infection may occur at any of a range of body sites; in general, HSV type 2 is associated with genital (and hence neonatal) infections; HSV type 1 accounts for most of the other forms. Incubation period: 2–12 (average 6) days. The disease varies from subclinical to severe, and is occasionally fatal. HSV can remain latent in nerve cells near the site of infection; reactivation may occur spontaneously or in response to other infections, stress, immunosuppression etc. In general, recurrent episodes become progressively less severe and less frequent. In neonates and immunodeficient individuals HSV may become disseminated and may involve e.g. the liver, adrenal glands, brain etc. Cutaneous herpes. Skin lesions may occur on any part of the body, often in clusters which may coalesce. Other symptoms of primary infection may include pain, fever, oedema etc. HSV type 1 tends to be associated with skin lesions above the waist, type 2 with those below the waist. (See also ECZEMA and PARONYCHIA.) Encephalitis. HSV type 1 is a common cause of non-epidemic viral ENCEPHALITIS. Onset is acute, with headache, nausea, vomiting, fever, myalgia, mental deterioration, convulsions, coma etc.; the fatality rate is typically >50%. Neurological sequelae are common in survivors. (See also aseptic MENINGITIS.) Genital herpes (herpes genitalis) is a SEXUALLY TRANSMITTED DISEASE which usually involves HSV type 2. It may be mild and self-limiting. Lesions occur in the genital region and may spread to adjacent areas of skin (e.g. buttocks, thighs). Other symptoms may include e.g. fever, dysuria, pain, malaise. In women the cervix may be the main site of genital infection (herpetic cervicitis); this may be asymptomatic, or there may be ulceration with hyperplasia. (HSV type 2 infection in women is associated with an increased risk of abortion and of cervical cancer.) Genital infections may give rise to subclinical shedding of virus, with associated risk of transmission. Labial herpes (herpes labialis) is typically a recurrent lip lesion (cf. COLD SORE) which usually crusts and heals in 3–10 days. Labial herpes may be associated with lip cancer. Neonatal herpes is usually acquired (during birth) from a mother with genital herpes – hence HSV type 2 is commonly responsible. Herpetic vesicles or ulcers, or keratoconjunctivitis, may or may not be present. Fatality rates may be 50% or more in untreated cases; surviving infants commonly exhibit neurological and/or ocular sequelae. (See also TORCH DISEASES.) Ocular herpes. HSV infection of the eye is a recurrent, usually unilateral, keratitis, sometimes with conjunctivitis; corneal scarring can lead to blindness. The characteristic lesion is a dendritic (branching) corneal ulcer with can be readily stained with either FLUORESCEIN or ROSE BENGAL [photograph of stained lesion: Book ref. 224, pp 67–68]. Oral herpes (herpetic stomatitis) occurs as a manifestation of initial HSV infection in adults and children. Primary herpetic gingivostomatitis involves shallow vesicular and ulcerative lesions on the labial and buccal mucosa, and tongue, with GINGIVITIS, fever and regional lymphadenopathy. The lesions usually heal in 7–10 days. Reactivation rarely involves the oral mucosa (except in immunocompromised individuals, in whom the oral lesions may be atypical in appearance). (Oral lesions may also be due to infection with the varicella zoster virus (VZV); in

chickenpox, such lesions may appear before development of the characteristic skin lesions.) [Virology of the mouth (including HSV infections): RMM (1994) 5 209–216.] Lab. diagnosis. For infections other than encephalitis: scrapings from the edges of lesions, or biopsies from skin or liver, are examined microscopically for multinucleate giant cells with eosinophilic intranuclear inclusion bodies; HSV can be demonstrated e.g. by immunofluorescence techniques, ELISA etc. For encephalitis, laboratory diagnosis may be made e.g. by PCR-based examination of cerebrospinal fluid (CSF), thus avoiding the risks of brain biopsy [see e.g. JCM (1997) 35 691–696]. The PCR-based detection of HSV (types 1 and 2) may be facilitated by a commercial system involving the use of MOLECULAR BEACON PROBES that hybridize to amplicons of both HSV type 1 and HSV type 2 (HSVision ; Stratagene). (HSV type 2 is not a common cause of viral encephalitis; it may be a causal agent e.g. in immunocompromised individuals.) Chemotherapy. A number of antiviral agents (e.g. ACYCLOVIR, IDOXURIDINE, PENCICLOVIR, trifluorothymidine, VIDARABINE) are active against HSV and are useful in some cases; for example, vidarabine has been used in cases of HSV encephalitis, while acyclovir, or penciclovir, is used in creams for the topical treatment of lesions on skin and mucous membranes. In general, such agents are not effective in preventing recurrence or transmission. herpes simplex virus group See ALPHAHERPESVIRINAE. herpes zoster A human disease resulting from the reactivation of a latent human (alpha) herpesvirus 3, present in a dorsal nerve ganglion, subsequent to an attack of CHICKENPOX that may have occurred (many) years earlier. The virus replicates in the ganglion, and in adjacent nervous tissue, and is transported, within the axon, to nerve endings in the corresponding region of skin; viral replication is believed to account for pain experienced during the acute phase of the disease – the pain being accompanied by an eruption of characteristic clusters of vesicular lesions. (Lesions may develop in areas not served by the affected nerves; this is thought to be due to viral dissemination in the bloodstream.) (See also RAMSAY HUNT SYNDROME.) Reactivation of the virus may occur spontaneously or may be provoked e.g. by immunosuppression, certain drugs, or other diseases. Post-herpetic neuralgia (PHN) is prolonged pain which appears to be due to damage sustained by the peripheral nervous system as a result of viral replication. Some regard PHN as pain which persists following the disappearance of the rash, while others have defined PHN as e.g. pain which persists for at least 30 days from the onset of the rash. In an attempt to provide a usable definition (for clinical trials of antiviral agents), the concept of zoster-associated pain (ZAP) has been introduced; ZAP includes the continuum of acute and chronic pain. Chemotherapy. The use of antiviral agents in the acute phase of herpes zoster is generally beneficial, and is particularly important in immunocompromised patients in whom herpes zoster may become a life-threatening condition; in the latter patients, intravenous ACYCLOVIR is the first-choice therapy (which may decrease the risk of dissemination). For immunocompetent patients with moderate to severe pain during the acute phase, systemic antiviral therapy should reduce the duration of the rash and pain if given immediately after the onset of the rash (within a maximum of 72 hours after onset); useful drugs: ACYCLOVIR, FAMCICLOVIR, VALACICLOVIR (each of which can be administered orally). Acyclovir should be given intravenously if severe complication (e.g. encephalitis) develop. [Treatment of zoster: RMM (1995) 6 165–174.] 365

Herpesviridae Herpesviridae A large family of enveloped VIRUSes containing a linear dsDNA genome. All herpesviruses are structurally similar: the virion (ca. 120–200 nm diam.) contains a core, i.e. a DNA–protein complex, within an icosahedral capsid (ca. 100–110 nm diam.; 12 pentameric and 150 hexameric capsomers) [capsid protein (structure): EMBO (2003) 22 757–765]; the nucleocapsid is enclosed by a lipoprotein envelope (bearing glycoprotein projections at the surface) – the (apparently) amorphous region (tegument) between capsid and envelope containing virus-encoded proteins. Virions are readily inactivated by lipid solvents, lipases or heat. Herpesviruses have been isolated from a wide range of animals, including mammals, birds, reptiles, amphibians and fish; some of the viruses have a narrow host range. Many herpesviruses can cause disease in their primary host(s). Many (possibly all) can remain latent in the host’s tissues, often for the lifetime of the host. The transmission of herpesviruses commonly occurs by direct contact between mucosal surfaces – but some can be transmitted via body fluids, such as milk, or via the placenta etc. (See also DNA TUMOUR VIRUSES.) The herpesvirus genome ranges from ∼125 to ∼240 kb in length and it characteristically contains repeated terminal and/or internal sequences which can take part in recombinational events (and which may therefore allow the development of variant forms of the genome). In the large genome (e.g. ∼80 genes in EPSTEIN–BARR VIRUS), most of the genes encode structural or regulatory functions; relatively few genes are expressed during viral latency. Interestingly, in some human herpesviruses the genome contains sequences that are partially homologous to certain CYTOKINES and/or cytokine receptors. Herpesviruses may be typed (fingerprinted) by techniques such as RFLP for epidemiological and other purposes [e.g. molecular epidemiology of herpes simplex virus type 1: RMM (1998) 9 217–224]. Replication cycle. Initially, the virion attaches to a host cell and the viral envelope then fuses with the cell membrane (see ENVELOPE). The nucleocapsid is transported across the cytoplasm to the nuclear membrane where the DNA is released into the nucleus via a nuclear pore. Within the nucleus, the viral immediate–early genes are transcribed, and the transcripts enter the cytoplasm for synthesis of viral polypeptides. Products of the immediate–early genes include proteins that serve regulatory functions and which are necessary for the expression of early genes (encoding e.g. a DNA polymerase) and late genes (encoding e.g. components of the capsid). Viral DNA is replicated, and the nucleocapsids are assembled, in the nucleus, with various structural proteins that enter the nucleus from the cytoplasm. Nucleocapsids can leave the nucleus in two ways. They can bud through the inner lamella of the nuclear membrane, thus acquiring an envelope; in this case, the mature virions are transported to the cell surface within membrane-bounded vacuoles and are then released to the exterior. Alternatively, nucleocapsids may enter the cytoplasm in an immature form which, only later, acquires an envelope by budding into a cytoplasmic vacuole. Classification and nomenclature. Some of the (many) known herpesviruses have been allocated to one of three subfamilies: ALPHAHERPESVIRINAE, BETAHERPESVIRINAE and GAMMAHERPESVIRINAE [Book ref. 23, pp 47–51] – mainly on the basis of biological characteristics. The naming of individual herpesviruses has been complicated by the widespread use of common names which are based on a

variety of criteria – such as the disease caused by the virus (e.g. Marek’s disease virus, herpes simplex virus); CPEs induced by the virus (e.g. cytomegalovirus); host species (e.g. Herpesvirus saimiri ); names of pioneer workers (e.g. Epstein–Barr virus, Luck´e virus). It has been recommended [Book ref. 139, pp 1–23] that the name of a herpesvirus should usually be based on the family or subfamily to which its primary host belongs (subfamily for bovine and primate viruses, family in other cases) – viruses isolated from humans being prefixed by ‘human’; the name may, where applicable, indicate the subfamily of herpesviruses to which the virus belongs (alpha, beta or gamma), and is followed by a number – numbers being allocated sequentially as new viruses are discovered. Thus, e.g. Marek’s disease virus becomes gallid herpesvirus 1; herpes simplex type 1 virus becomes human (alpha) herpesvirus 1; Epstein–Barr virus becomes human (gamma) herpesvirus 4. Many herpesviruses, including some important pathogens of animals, were not listed in an earlier (1982) classification scheme [Book ref. 23, pp 47–51]. These viruses include e.g. bovine herpesvirus 1 (causal agent of various cattle diseases, such as INFECTIOUS BOVINE RHINOTRACHEITIS, encephalitis in newborn calves, infectious pustular vulvovaginitis and abortion in cows etc.); anatid herpesvirus 1 (= anserid herpesvirus1, causal agent of DUCK VIRUS ENTERITIS); gallid herpesvirus 3 (causal agent of AVIAN INFECTIOUS LARYNGOTRACHEITIS); herpesviruses of amphibians (e.g. Luck´e virus, causal agent of renal adenocarcinoma in frogs, Rana pipiens) [review: Book ref. 140, pp 367–384]; and herpesviruses of reptiles and fish (see e.g. CARP POX and CHANNEL CATFISH VIRUS DISEASE) [review: Book ref. 140, pp 319–366]. Herpesvirus ateles See GAMMAHERPESVIRINAE. herpesvirus B Syn. B VIRUS. Herpesvirus saimiri See GAMMAHERPESVIRINAE. Herpesvirus simiae Syn. B VIRUS. herpetic Pertaining to or caused by a herpesvirus – see e.g. HERPES SIMPLEX. herpetic cervicitis See HERPES SIMPLEX. herpetic stomatitis See HERPES SIMPLEX. Herpetomonas A genus of homoxenous parasitic protozoa (family TRYPANOSOMATIDAE) which occur (typically in the gut) in flies, bugs and hymenopterous insects. Promastigote, paramastigote and opisthomastigote forms occur during the life cycle; biflagellate organisms may result from rapid division of promastigotes. Herpetosiphon A genus of GLIDING BACTERIA (see CYTOPHAGALES) which occur in aquatic (freshwater to marine) habitats. The organisms are gliding filaments (up to ca. 2 µm wide) which may be sheathed; they typically contain carotenoid glycoside pigments ranging from yellow or orange. Metabolism appears to be chemoorganotrophic. GC%: ca. 44–53. Herpetosoma A subgenus of TRYPANOSOMA within the STERCORARIA; species include parasites of rodents and man. The trypomastigote form typically has a subterminal kinetoplast, a pointed posterior end, and a free flagellum. T. (H.) lewisi, a parasite in rats, is transmitted cyclically and contaminatively by fleas, e.g. Xenopsylla cheopis; it is cultivable e.g. in NNN medium at 25–27° C. In the vertebrate host, the reproductive forms (epimastigotes) undergo multiple fission or unequal binary fission, resulting eventually in the production of non-dividing trypomastigotes. T. (H.) rangeli is parasitic in man (and in e.g. cats, dogs etc) in Central and South America, and is transmitted cyclically – mainly by bugs of the genus Rhodnius. Although classified in the Stercoraria, this species is transmitted by bite: the 366

heterokont helps to maintain the anaerobic state. [Protection of nitrogenase from oxygen in heterocystous cyanobacteria: MR (1992) 56 352–362.] In Anabaena strain PCC 7120, which forms heterocysts in both terminal and intercalary locations, differentiation of heterocysts depends on a functional hetR gene. In genetically engineered cells of this strain, controlled expression of hetR can induce differentiation of heterocysts even under conditions that would normally repress their formation. However, in cells with a mutant patA gene – which form heterocysts almost exclusively at terminal locations – the expression of hetR did not induce the formation of intercalary heterocysts; this was interpreted to mean that, while raised levels of HetR are necessary to promote the formation of heterocysts, PatA may play a role in regulating the expression of hetR [PNAS (2001) 98 2729–2734]. During nitrogen fixation, the heterocysts and vegetative cells are metabolically interdependent. The vegetative cells supply heterocysts with e.g. fixed carbon, reduced sulphur, and glutamate; in the heterocyst, fixed nitrogen is transferred to glutamate by glutamine synthetase (see AMMONIA ASSIMILATION), and the resulting glutamine is passed back to vegetative cells to supply their nitrogen requirements. Communication between a heterocyst and adjacent vegetative cell(s) occurs via fine pores (microplasmodesmata) in their juxtaposed cytoplasmic membranes; juxtaposition of these membranes occurs at the vegetative-cell end of a channel (the pore channel ) which passes through the thick heterocyst envelope. (Microplasmodesmata are also found between vegetative cells.) [Heterocyst differentiation and function: Book ref. 75, pp. 219–242, 265–280.] heterocytotropic antibodies CYTOPHILIC ANTIBODIES (particularly REAGINIC ANTIBODIES) which can attach to the cells of two or more different host species. (cf. HOMOCYTOTROPIC ANTIBODIES.) heteroduplex Any double-stranded nucleic acid in which some, or many, of the bases in one strand are not complementary to bases in the corresponding positions in the other strand; such mismatching of base pairs is reflected in the thermal stability of the duplex. (See also DNA HOMOLOGY and HOMODUPLEX.) The term ‘heteroduplex’ is also used for any duplex in which each strand originates from a different parent duplex (see e.g. RECOMBINATION), even though such strands may in some cases be strictly complementary. heteroecious Syn. HETEROXENOUS. heterofermentation (1) Any fermentation in which there is more than one major end-product. (2) Syn. HETEROLACTIC FERMENTATION. heterogeneous nuclear RNA See HNRNA. heterogenote See MEROZYGOTE. heteroglycan See POLYSACCHARIDE. heteroimmune phages See SUPERINFECTION IMMUNITY. heteroimmunization The stimulation of an immune response to antigens derived from another species. (cf. ISOIMMUNIZATION.) heterokaryon (heterocaryon) (mycol.) A hyphal cell, mycelium, organism, or spore which contains genetically different nuclei. (cf. HOMOKARYON.) heterokaryosis (mycol.) The condition in which genetically different nuclei exist in the same cell, mycelium or spore; it may arise e.g. by the entry of a genetically different nucleus into a HOMOKARYON (e.g. by hyphal fusion) or by mutation in a binucleate or multinucleate homokaryotic cell or mycelium. Heterokaryosis is important e.g. in PARASEXUAL PROCESSES. heterokont Refers to a pair of flagella (on a biflagellate cell) in which one flagellum differs from the other in length and often also in type: see e.g. XANTHOPHYCEAE. (cf. ISOKONT.)

organism develops both in the gut and (as epimastigotes and trypomastigotes) in the salivary glands of the vector, but forms which develop in the gut are not infective for mammals. In man, bloodstream forms are trypomastigotes, ca. 25–35 µm in length. T. (H.) rangeli appears to be non-pathogenic. It can be cultivated e.g. in NNN medium. Other species include T. microti, T. nabiasi and T. zapi. Herpomyces See LABOULBENIALES. Herxheimer reaction Syn. JARISCH–HERXHEIMER REACTION. Hessea See MICROSPOREA. Hesseltinella See MUCORALES. heteroantibody Any antibody formed in one species against an antigen derived from another species. (cf. ISOANTIBODY.) heteroauxin See AUXINS. Heterobasidion A genus of fungi of the APHYLLOPHORALES (family Polyporaceae). H. annosum (formerly Fomes annosus) forms perennial, bracket-shaped or resupinate, typically corky or woody fruiting bodies in which the context is dimitic and lacks clamp connections; the bracket-shaped fruiting body typically has a rust-coloured upper surface and a pale, porous, lower surface. Fruiting bodies of several years’ standing consist of vertically stacked (‘stratified’) layers of vertically orientated tubules. Basidiospores: spheroidal, colourless, ca. 5 × 4 µm. H. annosum grows on felled timbers, and is parasitic on conifers and e.g. red oak (Quercus borealis); in e.g. parts of the United Kingdom, the stumps of freshly-felled trees are inoculated with Peniophora gigantea which colonizes the cut surface, inhibiting infection by H. annosum. (See also TIMBER SPOILAGE.) heterocaryon Syn. HETEROKARYON. Heterochlorida See PHYTOMASTIGOPHOREA. Heterochloris See XANTHOPHYCEAE. heterochromatin See CHROMATIN. heteroclicity The phenomenon in which a cross-reactive antigen binds an antibody with an AFFINITY greater than that shown by the homologous antigen; the cross-reactive antigen, and the antibody, are described as heteroclitic. heteroclitic See HETEROCLICITY. heterococcolith See COCCOLITH. heterocyst A type of cell, morphologically and functionally distinct from a vegetative cell, which occurs under certain conditions in some filamentous CYANOBACTERIA (members of sections IV and V); heterocysts function as specialized anaerobic compartments within which NITROGEN FIXATION can occur in aerobic environments. (cf. AKINETE.) Heterocysts differentiate from vegetative cells (intercalary or terminal, depending on species) in response to limiting levels of combined nitrogen; differentiation is inhibited in the presence of e.g. nitrate and ammonia. Mature heterocysts apparently cannot divide. Differentiation from a vegetative cell involves e.g. (i) the formation of a thick, multilayered envelope – whose thickness (in Anabaena flos-aquae) has been found to increase with increased partial pressure of oxygen [JGM 1992) 138 2673–2678]; (ii) rearrangement of thylakoid membranes (heterocysts are filled with contorted membranes); (iii) inactivation of photosystem II, resulting in the cessation of oxygen evolution – cyclic photophosphorylation (which involves photosystem I) apparently continues to occur; (iv) degradation of phycocyanin (see PHYCOBILIPROTEINS); (v) cessation of carbon dioxide fixation (e.g. by inactivation of RuBP carboxylase); (vi) synthesis of NITROGENASE (see NIF GENES). [Role of transcription in differentiation: JGM (1984) 130 789–796]. Respiratory activity apparently 367

Heterokontae heteroresistance (1) The resistance (of an organism) to two or more related antibiotics – e.g. two or more b-lactam antibiotics. (2) See MRSA. heterothallism The phenomenon in which sexual reproduction requires the involvement of two different thalli – an individual thallus being self-sterile even when (as is common) it is hermaphroditic; gametes etc which can unite sexually are said to be compatible. (cf. HOMOTHALLISM; see also COMPATIBILITY sense 2.) In morphological heterothallism (= dioecism) compatibility is determined solely on a sexual basis: there are separate male and female thalli, and sexual reproduction can occur between any male thallus and any female thallus of the same species. Dioecism is uncommon among fungi; it occurs e.g. in some species of Achlya and of Laboulbenia. In physiological heterothallism male and female organs generally occur on the same thallus, and in these cases compatibility is determined not only on a sexual (male–female) basis: sexual union can occur between male and female gametes etc only if each has appropriate mating type allele(s) (see MATING TYPE); gametes etc which have the same mating type allele(s) cannot unite sexually and are said to be incompatible. In e.g. many zygomycetes, male and female organs are not distinguishable; in such cases sexually compatible thalli are often designated ‘plus’ and ‘minus’. In bipolar physiological heterothallism compatibility is determined at one mating type locus which may contain either of 2 alleles; if these alleles be designated A and a, then mating can occur between one individual (mating type) which has the A allele and another which has the a allele. Bipolar heterothallism is also called one-locus two-allele heterothallism, unifactorial heterothallism (since only one locus is involved), or DIMIXIS (since two alleles are involved). In tetrapolar physiological heterothallism compatibility is determined at two mating type loci, each locus containing one of two alleles. If these loci be designated A, B (with alleles a, b, respectively), four mating types can be distinguished: AB, Ab, aB and ab. Mating can occur only between individuals which contain complementary alleles at both loci; thus, e.g. mating can occur between AB and ab individuals, and between Ab and aB individuals. Tetrapolar heterothallism is also called bifactorial heterothallism. In some cases of one- and two-locus heterothallism, a locus may be occupied by any allele of an allelomorphic series; in such cases there can be many mating types. (See also DIAPHOROMIXIS.) Heterothallism provides a constraint on inbreeding, and consequently increases the potential for genetic reassortment within a species. Heterotrichida An order of free-living and parasitic ciliate protozoa (class POLYHYMENOPHOREA) in which the organisms are typically large, often contractile (see MYONEME), and sometimes pigmented, and in which somatic ciliature is commonly abundant and oral ciliature is well developed. Genera include e.g. Balantidioides, BLEPHARISMA, Brachonella, Bursaria, Condylostoma, Metopus, SPIROSTOMUM and STENTOR. heterotrichous (1) Having different types of cilia or flagella. (2) Of certain filamentous algae: having a vegetative thallus consisting of both prostrate and erect systems of filaments (as e.g. in CHAETOPHORA). heterotroph An organism which uses organic compounds for most or all of its carbon requirements. (cf. AUTOTROPH; ORGANOTROPH.) The term ‘heterotroph’ is often used to refer specifically to CHEMOORGANOHETEROTROPHS – although chemolithotrophs and phototrophs may also be heterotrophic.

Heterokontae Former taxon for the xanthophytes. heterolactic fermentation A type of LACTIC ACID FERMENTATION in which sugars (e.g. lactose, glucose) are fermented to a range of products. There are two distinct pathways, phosphoketolase being a key enzyme in each. The ‘classical’ (6-phosphogluconate) pathway occurs in certain LACTIC ACID BACTERIA (e.g. Leuconostoc spp, betabacteria – e.g. Lactobacillus brevis): glucose is fermented to lactic acid, CO2 , and acetic acid and/or ethanol (the ratio of acetic acid to ethanol depending e.g. on the redox potential of the system); PENTOSES are fermented to lactic and acetic acids [Appendix III(b)]. In the Bifidobacterium (‘bifidus’) pathway the products of glucose fermentation are lactic and acetic acids in the molar ratio 2:3 [Appendix III(b)]. heterologous (1) Derived from or associated with a species different from that being referred to (cf. HOMOLOGOUS (2)). (2) See ALTERNATION OF GENERATIONS. (3) (immunol.) Of an antibody (or antigen): one which is not HOMOLOGOUS (sense 4) to a given antigen (or antibody). A heterologous antibody, for example, may be a CROSS-REACTING ANTIBODY or may not combine at all with the given antigen. A heterologous vaccine is a vaccine prepared against one organism but capable of giving protective immunity against another. heterologous interference See INTERFERENCE (1). Heteromastix See MICROMONADOPHYCEAE. heteromerous (1) (lichenol.) Refers to a lichen thallus in which the photobiont is confined to a distinct layer within the thallus (see LICHEN). (2) (mycol.) In an agaric: refers to a pileus and stipe composed of two distinct types of cell: SPHAEROCYSTS and hyphae (see RUSSULALES). (3) (ciliate protozool.) See MACRONUCLEUS. (cf. HOMOIOMEROUS.) heteromixis Collectively: DIMIXIS, DIAPHOROMIXIS and secondary HOMOTHALLISM. heteromorphic Morphologically dissimilar. heteromorphic alternation of generations See ALTERNATION OF GENERATIONS. Heteronema A genus of EUGLENOID FLAGELLATES, closely related to PERANEMA, in which the second emergent flagellum is not attached to the pellicle. H. acus occurs e.g. in activated sludge. heterophil antibodies (heterophile antibodies) Antibodies which can combine with specific HETEROPHIL ANTIGENS. Such antibodies may occur in a host which has not had immunological contact with the corresponding antigen; e.g., patients with INFECTIOUS MONONUCLEOSIS usually develop heterophil antibodies which agglutinate the red blood cells of the sheep, horse and ox – species whose RBCs share a common heterophil antigen (see PAUL–BUNNELL TEST). heterophil antigen (heterophile antigen) Any antigen which occurs (in an identical or closely related form) in several or many widely differing species (e.g. sheep, horse). If introduced into a species in which it is normally absent, a heterophil antigen elicits the synthesis of HETEROPHIL ANTIBODIES. (See also FORSSMAN ANTIGEN.) heterophilic binding (of cell adhesion molecules) See IMMUNOGLOBULIN SUPERFAMILY. Heterophrys See CENTROHELIDA. heteroplasmon See CYTODUCTION. heteroploid Having a complement of chromosomes differing from that characteristic of the species. (cf. EUPLOID sense 2.) A heteroploid cell may be EUPLOID (sense 1) – e.g. a polyploid cell arising in a haploid or diploid population – or it may be ANEUPLOID. heteropolysaccharide See POLYSACCHARIDE. 368

high-dry objective heteroxenous (heteroecious) Refers to a parasite which carries out part of its life cycle in each of two or more different host species. (cf. HOMOXENOUS.) heterozygote A HETEROZYGOUS cell or organism. heterozygous Refers to a cell or organism (e.g. a diploid eukaryote or a bacterial MEROZYGOTE) in which one or more specified genes, or all of the genes, are present in the form of different ALLELES. (cf. HOMOZYGOUS.) hex genes See TRANSFORMATION (1). Hexacapsula See MYXOSPOREA. hexachlorophane (hexachlorophene) See BISPHENOLS. hexagonal II phase See CYTOPLASMIC MEMBRANE. hexamer See ICOSAHEDRAL SYMMETRY. hexamethylenetetramine See HEXAMINE. hexamine (hexamethylenetetramine; methenamine) A condensation product of ammonia and formaldehyde used as a urinary antiseptic. It has no intrinsic antimicrobial activity, but under acid conditions it slowly releases FORMALDEHYDE. It is not effective against urea-splitting bacteria since these produce ammonia which raises the pH of the urine. Hexamine is usually used with MANDELIC ACID (hexamine mandelate, Mandelamine) or with hippuric acid (Hiprex). Hexamita A genus of protozoa of the DIPLOMONADIDA. H. meleagridis is an important pathogen of turkeys (see HEXAMITIASIS); cells are pear-shaped, ca. 10 µm in length, with two anteriorly located nuclei, two clearly separate, parallel, longitudinal axostyles, and 8 flagella – two pairs orientated anteriorly, one pair laterally, and the fourth pair projecting posteriorly. H. intestinalis is a cyst-forming species which occurs e.g. in the cloaca of the frog. hexamitiasis An acute infectious disease of e.g. turkeys and pheasants (but not affecting chickens, ducks or geese); it is caused by Hexamita meleagridis. Infection occurs by ingestion of food, water etc contaminated with faeces from infected or carrier birds. Symptoms: listlessness; anorexia; passage of watery, frothy, foul-smelling stools; coma. Mortality rates are often very high in young birds. Survivors commonly become carriers. Treatment: e.g. furazolidone. (See also POULTRY DISEASES.) hexokinase An enzyme which phosphorylates various hexoses in the 6-position (see e.g. EMBDEN–MEYERHOF–PARNAS PATHWAY). hexon See ADENOVIRIDAE. hexose bisphosphate pathway Syn. EMBDEN–MEYERHOF–PARNAS PATHWAY. hexose monophosphate pathway (HMP pathway; HMP shunt; oxidative pentose phosphate pathway; pentose phosphate pathway/cycle; phosphogluconate pathway; Warburg–Dickens pathway) A metabolic pathway present in a wide range of prokaryotic and eukaryotic microorganisms as well as in plants and animals; it involves the oxidative decarboxylation of glucose 6-phosphate, via 6-phosphogluconate, to ribulose 5phosphate, followed by a series of reversible, non-oxidative interconversions whereby hexose and triose phosphates are formed from pentose phosphates. The generally accepted scheme for the HMP pathway is shown in Appendix I(b). The HMP pathway can serve various functions, the major ones probably being to provide NADPH (2 molecules per molecule of glucose converted to ribulose 5-phosphate) necessary for biosyntheses (e.g. of fatty acids), and to provide precursors for various biosynthetic pathways (e.g. pentoses for histidine and nucleotide biosynthesis [Appendices IV(g) and V], erythrose 4-phosphate for aromatic amino acid biosynthesis [Appendix IV(f)]). Fructose 6-phosphate may be converted to glucose 6-phosphate and re-enter the pathway, or may be converted to pyruvate via

reactions of the EMBDEN–MEYERHOF–PARNAS PATHWAY; similarly, glyceraldehyde 3-phosphate may be converted to pyruvate via the latter part of the EMP pathway. In organisms with a functional TCA CYCLE, pyruvate can be oxidized to yield energy via the TCA cycle and a respiratory chain. In organisms which lack a complete TCA cycle, pyruvate may be converted to acetyl-CoA and thence to acetic acid (as in some acetic acid bacteria). Alternatively, under certain conditions, glyceraldehyde 3-phosphate can be converted to glucose 6-phosphate (by reactions of GLUCONEOGENESIS) which can then re-enter the HMP pathway; in this case, for every six molecules of glucose entering the pathway, one molecule is effectively completely oxidized. If reducing equivalents from NADPH can be transferred to NAD+ (see TRANSHYDROGENASE) and thence to an electron acceptor via a respiratory chain, the pathway can be used to generate energy even in the absence of a TCA cycle. Other functions of the HMP pathway include the metabolism of those pentoses which can be converted to intermediates of the pathway. (See also RMP PATHWAY.) hexulose phosphate pathway Syn. RMP PATHWAY. hexuronic acids URONIC ACIDS corresponding to hexoses. hexylresorcinol See PHENOLS. hfl genes (in E. coli ) See BACTERIOPHAGE l. hflB gene See FTSH. Hfr donor High frequency recombination donor: a conjugal donor (see CONJUGATION sense 1b) created by the insertion of a CONJUGATIVE PLASMID (sense 1) into a bacterial chromosome. The chromosome of an Hfr donor can be mobilized by the plasmid so that chromosomal genes can be transmitted to a recipient during conjugation; thus, in a mixed population of recipients and Hfr donors, recombination between recipient and (transferred) donor DNA will occur at high frequency in the recipient population. The (relatively few) conjugative plasmids which can give rise to Hfr donors include the F PLASMID. A conjugative plasmid which cannot normally integrate into the bacterial chromosome may be able to do so if it first integrates e.g. with the genome of an A+ B − strain of BACTERIOPHAGE MU, integration of the plasmid–Mu complex into the chromosome then being mediated by Mu; a recipient mated with such an Hfr donor must be lysogenic for a c+ strain of Mu to avoid ZYGOTIC INDUCTION when the Mu prophage is transferred to the recipient. (See also PRIME PLASMID and INTERRUPTED MATING.) HFRS Haemorrhagic fever with renal syndrome (see HANTAVIRUS). HFT (of plasmids) See EPIDEMIC SPREAD. HFT lysate See TRANSDUCTION. HGV Hepatitis G virus (see HEPATITIS). HHV1 Human (alpha) herpesvirus 1 (see ALPHAHERPESVIRINAE). HHV2 Human (alpha) herpesvirus 2 (see ALPHAHERPESVIRINAE). HHV3 Human (alpha) herpesvirus 3 (see ALPHAHERPESVIRINAE). HHV4 Human (gamma) herpesvirus 4 (see GAMMAHERPESVIRINAE). HHV5 Human (beta) herpesvirus 5 (see BETAHERPESVIRINAE). HHV6 Human (beta) herpesvirus 6 (see BETAHERPESVIRINAE). HHV7 Human (beta) herpesvirus 7 (see BETAHERPESVIRINAE). HHV8 Human (gamma) herpesvirus 8 (see GAMMAHERPESVIRINAE). HI test HAEMAGGLUTINATION-INHIBITION TEST. HIB HAEMOLYTIC IMMUNE BODY. Hibitane See CHLORHEXIDINE. high-dry objective Any objective lens which has a numerical aperture between 0.65 and 0.95, and which is not used as an immersion lens. 369

high-fructose corn syrup high-fructose corn syrup A sweetening agent produced industrially from glucose by GLUCOSE ISOMERASE (see also IMMOBILIZATION). high-mobility group proteins See NON-HISTONE PROTEINS. high mutability gene Syn. MUTATOR GENE. high-performance liquid chromatography See CHROMATOGRAPHY. high-potential iron–sulphur protein See HIPIP. high-pressure liquid chromatography See CHROMATOGRAPHY. high zone tolerance See IMMUNOLOGICAL TOLERANCE. higher fungi Fungi of the subdivisions ASCOMYCOTINA, BASIDIOMYCOTINA and DEUTEROMYCOTINA. (cf. LOWER FUNGI.) Highlands J virus See ALPHAVIRUS. highly active antiretroviral therapy See HAART. HIGM See RNA EDITING. Hikojima variant See VIBRIO (V. cholerae). hilar appendix A small protuberance on a basidiospore near its region of attachment to the sterigma. Hildenbrandia See RHODOPHYTA. Hill reaction In PHOTOSYNTHESIS: light-dependent evolution of oxygen by isolated CHLOROPLASTS in the absence of CO2 but in the presence of e.g. ferric oxalate which acts as an electron acceptor for PS-II. hilum The mark, scar or small projection on a spore corresponding to the region at which it was formerly attached to the spore-bearing structure. him genes (in E. coli ) See BACTERIOPHAGE l. Himanthalia See PHAEOPHYTA. Himmelweit pipette A PASTEUR PIPETTE with a hole in the side of the capillary end; it is used e.g. in the harvesting of allantoic fluid from an EMBRYONATED EGG. hin gene See PHASE VARIATION. HindII A RESTRICTION ENDONUCLEASE from Haemophilus influenzae; GTPy/PuAC. HindIII A RESTRICTION ENDONUCLEASE from Haemophilus influenzae; A/AGCTT. HinfI See RESTRICTION ENDONUCLEASE (table). hinge region In the heavy chain of an IMMUNOGLOBULIN: the amino acid sequence at the junction of the Fd portion and the Fc portion; it appears to confer conformational flexibility on the molecule. Structurally, the hinge region is the most variable part of the ‘constant’ region of the heavy chain. In alpha and gamma chains (but not in mu chains) the hinge region is rich in proline. Hinozan (edifenphos; O-ethyl-S,S-diphenyl phosphorodithioate) An antifungal ORGANOPHOSPHORUS COMPOUND used as a protectant against rice blast disease; it can act e.g. as a powerful cutinase inhibitor (see CUTIN). hip gene (in E. coli ) See BACTERIOPHAGE l. HiPIP High-potential iron–sulphur protein: a type of IRON–SULPHUR PROTEIN which has a single [4Fe–4S] centre and a highly positive Em ; the HiPIP in Chromatium vinosum has an Em of +350 mV. hippurate hydrolysis Certain bacteria (e.g. Streptococcus spp, Campylobacter spp) produce a hippuricase which hydrolyses hippurate (C6 H5 .CO.NH.CH2 .CO2 − ) to benzoate and glycine. Hippuricase activity may be detected by adding a calculated amount of acid FeCl3 to a 4-day culture of the organism in a medium containing 1.0% sodium hippurate; the FeCl3 forms a persistent precipitate with benzoate (positive test). (A precipitate is also formed with hippurate, but this is more soluble with excess FeCl3 ; the amount of FeCl3 used in the test is that which just dissolves the hippurate precipitate initially formed in an uninoculated control tube on dropwise addition of the

reagent.) In a quicker method, a solution of sodium hippurate is heavily inoculated with the test organism; after incubation (37° C/2hours), ninhydrin reagent is added. A deep purple colour indicates the presence of glycine (positive test). [Methods: Book ref. 2, p. 416.] Hiprex See HEXAMINE. hircinol A dihydroxyphenanthrene PHYTOALEXIN produced by the orchid Loroglossum hircinum in response to infection with e.g. Rhizoctonia spp. (cf. ORCHINOL.) Hirst spore trap (automatic volumetric spore trap) An instrument used e.g. for sampling the airborne microflora. (See also AIR.) Air, drawn in through a vertical slit in an upright cylindrical housing, strikes a slowly-moving greased microscope slide or, in the modern version (Burkard trap), a slowly-rotating drum coated with transparent adhesive tape; the slit is kept facing into the wind by a vane attached to the housing. Hirsutella A genus of fungi of the HYPHOMYCETES. Most species are entomopathogenic; H. thompsonii infects mites. his operon (histidine operon) An OPERON (located at ca. 44 min on the chromosome of Escherichia coli ) which contains 9 structural genes (hisGDCBHAFIE ) encoding enzymes necessary for the biosynthesis of histidine [Appendix IV(g)]. The transcription of the his structural genes is inversely related to the level of histidyl-tRNA in the cell. Regulation is apparently achieved solely by attenuation (see OPERON, cf. TRP OPERON); the sequence encoding the leader peptide contains seven successive histidine codons. HisJ, HisM, HisP, HisQ See BINDING PROTEIN-DEPENDENT TRANSPORT SYSTEM. hispid Bearing hairs, bristles or spines. Hispid flagellum: see FLAGELLUM (b). Hiss serum water A medium made by mixing 1 volume of serum (horse, ox or sheep) with 3 volumes of water, and adding phenol red and a sugar (final concentrations ca. 0.0025% and 1.0%, respectively). histamine An amine formed by the decarboxylation of histidine; it occurs e.g. in MAST CELLS and is involved in ANAPHYLACTIC SHOCK and INFLAMMATION. (See also ANAPHYLATOXINS.) Histamine causes contraction of e.g. tracheobronchial and intestinal smooth muscle, and increases vascular permeability in the skin and other regions by acting as a vasodilator of terminal arterioles and as a vasoconstrictor of postcapillary venules. [Agents that release histamine from mast cells: ARPT (1983) 23 331–351.] The microbial production of toxic amounts of histamine in certain foods has been implicated as a cause of food poisoning: for example, Lactobacillus buchneri can produce histamine in Swiss cheese [AEM (1985) 50 1094–1096] (see also FISH SPOILAGE). histamine-sensitizing factor Syn. PERTUSSIS TOXIN. histidase See HISTIDINE DEGRADATION. L-histidine biosynthesis See Appendix IV(g); see also HIS OPERON. histidine degradation Histidine can be used as a substrate by various bacteria; in e.g. Pseudomonas aeruginosa histidine is initially deaminated by histidase to urocanate which is eventually degraded to glutamate and formate. Some bacteria can decarboxylate histidine to histamine: see e.g. FISH SPOILAGE. (See also BINDING PROTEIN-DEPENDENT TRANSPORT SYSTEM.) histidine kinase A KINASE whose active site contains a histidine residue. (See also CHEMOTAXIS and TWO-COMPONENT REGULATORY SYSTEM.) [Histidine kinases and signal transduction (review): TIG (1994) 10 133–138.] histidine operon Syn. HIS OPERON. 370

HIV histidine permease See BINDING PROTEIN-DEPENDENT TRANSPORT SYSTEM. histiocyte A MACROPHAGE which occurs in extravascular tissues. histocompatibility restriction (MHC restriction) The restriction on (physical) cell–cell interaction, involving cells of the immune system, imposed by the need for such cells to have, or to recognize, particular MHC-specified cell-surface antigens as a prerequisite for interaction. histolyticolysin See THIOL-ACTIVATED CYTOLYSINS. Histomonas A genus of protozoa of the TRICHOMONADIDA. H. meleagridis is the causal agent of BLACKHEAD in turkeys. Intracellular cells of H. meleagridis are spherical to ovoid, nonflagellate (though they contain kinetosomes), ca. 10–15 µm; they exhibit amoeboid motility. Within the caecal lumen of the turkey, cells of H. meleagridis (ca. 10–25 µm) may exhibit both amoeboid and flagellar motility, each cell having 1–4 flagella (commonly one). histomoniasis Syn. BLACKHEAD. histone-like proteins Bacterial DNA-binding proteins believed to resemble the HISTONES associated with eukaryotic DNA. (Compare HU PROTEIN.) histones Basic proteins, rich in arginine and/or lysine, which are major components of CHROMATIN in most eukaryotes. (cf. DINOFLAGELLATES.) The main classes of histones are designated H1 (‘lysine-rich’), H2A and H2B (‘slightly lysine-rich’), and H3 and H4 (‘arginine-rich’). Histones interact with DNA primarily via salt bridges between the positively-charged arginine/lysine residues and the negatively-charged phosphate groups of the DNA. Constitutive histone variants can effect changes in chromatin structure and dynamics that affect e.g. DNA replication, repair and transcription [GD (2005) 19 295–316]. Histoplasma A genus of fungi of the HYPHOMYCETES; teleomorph: AJELLOMYCES. H. capsulatum, the causal agent of HISTOPLASMOSIS, is a dimorphic fungus which occurs e.g. in soil that is contaminated with the droppings of birds, bats and other animals. At room temperature or e.g. 25° C, H. capsulatum forms white to golden, cottony, septate mycelium, but at 37° C it forms ovoid, budding, yeast-like cells 2–4 µm (var. capsulatum) or 8–15 µm (var. duboisii ); in vivo, grape-like clusters of cells may occur in macrophages or in regions of caseation. H. capsulatum gives rise to microconidia (2–5 µm) and macroconidia (ca. 8–15 µm), the latter (also called ‘chlamydospores’) typically bearing short, finger-like projections. H. farciminosum. See EPIZOOTIC LYMPHANGITIS. (See also ENDOCARDITIS and PAS REACTION.) histoplasmin test A SKIN TEST, analogous to the TUBERCULIN TEST, used in the diagnosis of HISTOPLASMOSIS; it involves the intradermal injection of histoplasmin (a filtrate of a mycelial culture of Histoplasma capsulatum). The skin usually becomes reactive to histoplasmin within one to two months of the onset of disease, and reactivity may persist for many years; crossreactions with other fungal antigens (e.g. coccidioidin) occur. histoplasmosis (Darling’s disease) A disease of man and animals, found worldwide, caused by Histoplasma capsulatum (cf. EPIZOOTIC LYMPHANGITIS). Infection occurs by inhalation of spores (e.g. from disturbed soil). The disease may be subclinical, acute or chronic. The acute condition may resemble a common cold or influenza. In the chronic condition, granulomatous, inflamed lesions occur in the lungs; the primary lesion may become inactive and calcify on healing. The primary infection is usually self-limiting, but occasionally progressive lung disease occurs and may eventually be fatal due e.g. to loss of

lung function or to secondary bacterial infection. Infrequently, histoplasmosis becomes disseminated (usually in young children or in the elderly, debilitated or immunocompromised); lesions may occur in lymph nodes, liver, spleen, intestine, skin, heart, kidneys, CNS etc. Disseminated histoplasmosis is often rapidly fatal. Lab. diagnosis: serological tests (e.g. a CFT); microscopic and cultural examination of clinical specimens. Chemotherapy: e.g. amphotericin B, ketoconazole. histotope A site on an MHC class I or II antigen recognized by a T lymphocyte. histozoic Living (parasitic) within tissues. (cf. COELOZOIC.) Histriculus See HYPOTRICHIDA. hit-and-run oncogenesis Oncogenesis which is initiated by a particular agent (e.g. a virus) but, once initiated, can proceed in the absence of the initiating agent. HIV Human immunodeficiency virus, infection with which can give rise to AIDS (q.v.). HIV is a retrovirus (family RETROVIRIDAE) classified within the subfamily LENTIVIRINAE. HIV was previously referred to as AIDS-associated retrovirus (ARV), ‘HTLVIII’ (cf. HTLV), immunodeficiency-associated virus (IDAV) and lymphadenopathy-associated virus (LAV). Evidence for the involvement of HIV in AIDS was obtained in 1983 [Science (1983) 220 868–871]. Subsequently a distinct, but related, retrovirus was detected in AIDS patients in West Africa [Nature (1987) 326 662–669]. These two viruses are now designated HIV-1 and HIV-2 respectively. HIV-1 and HIV-2 are similar in both structure and genome. The origin of HIV is unknown. One hypothesis supposes that the major (M) strain of HIV arose through the use of an antipoliomyelitis vaccine that had been prepared by culturing polio virus in non-human primate cells; it is proposed that a simian strain of immunodeficiency virus (initially present in the culture cells) contaminated the vaccine and (thus) entered the vaccinated human population (located mainly in the Congo) in the late 1950s. Subsequent studies on viruses from the Congo area do not support this hypothesis [Nature (2001) 410 1047–1048]. The HIV virion is ∼100 µm in diameter. Its innermost region consists of a cone-shaped core that includes (i) two copies of the (positive-sense) ssRNA genome, (ii) the enzymes REVERSE TRANSCRIPTASE, integrase and protease, (iii) some minor proteins, and (iv) the major core protein. The core is surrounded by a protein matrix, and the whole is enclosed within an envelope (a lipid bilayer); the envelope is penetrated by a number of ‘spikes’ (gp41), each spike bearing a distal (outermost) trimeric glycoprotein (gp120). [Fine structure of HIV: Virol. (1987) 156 171–176.] The genome (∼9.2 kb) includes sequences corresponding to the gag, pol and env regions of other exogenous retroviruses (see RETROVIRIDAE). The gag region encodes structural proteins, including the major core protein (p24) and the matrix protein (p17). The pol region encodes regulatory proteins: REVERSE TRANSCRIPTASE, protease (involved in the maturation of virions), RNASE H and integrase. (The enzymes reverse transcriptase and protease are major targets for antiretroviral drugs.) The env region encodes the envelope-associated proteins, gp120 (required for initial binding of virus to target cell) and gp41 (involved in fusion of the viral envelope with the membrane of the target cell). Other HIV genes include: tat and rev (whose products are needed for viral replication); vif (‘viral infectivity factor’); and vpu (whose product promotes efficient budding of the (HIV-1) virion during productive infection of a cell). (See also Rev in GENE THERAPY.) 371

HIV-positive The LTR also includes a regulatory region for polyadenylation of transcripts. Synthesis of viral mRNA, and of genomic RNA, is carried out by the host’s RNA polymerase. Viral envelope proteins are translocated to, and insert into, the cell membrane (with gp120 located at the outer surface). The assembled core acquires an envelope by budding through the cell membrane. Culture. Culture may be useful e.g. for diagnosis of HIV infection in neonates; in these young patients the presence of anti-HIV antibody may simply reflect acquisition from an HIV-positive mother. Cultures of HIV characteristically exhibit CPE (cytopathic effects), including the formation of giant multinucleated cells and cell lysis. Culture can be carried out in CD4+ T cells; the virus can also infect other types of cell such as monocytes and promyelocytes [Virol. (1985) 147 441–448]. HIV may give rise to a persistent, non-cytopathic and productive (virion-producing) infection of human CD4+ T cells in culture [Science (1985) 229 1400–1402]. Inactivation of HIV by disinfection. Hypochlorite (effective conc. 10000 parts per million available chlorine) is a useful disinfectant. Glutaraldehyde (dangerous chemical!!!) has been used for disinfecting surfaces in a wellventilated environment; safety regulations must be observed. Phenolics and ethanol are unsuitable. In serum, inactivation of HIV may require more than 30 minutes at 56° C [e.g. Book ref. 219, p 814]. Genetic variability of HIV isolates. Isolates of HIV from different patients tend to be genetically heterogeneous, particularly in the env sequence [minireview: Cell (1986) 46 1–4], and variation may also be observed in isolates obtained sequentially from the same patient over a period of time [Science (1986) 232 1548–1553]. As env encodes the (antigenic) viral surface protein gp120, such ANTIGENIC VARIATION presents a problem for the development of an effective anti-HIV vaccine; in this context, studies have been carried out to determine the effect of genetic variation on the immunogenetic potential of gp120 [Arch. Virol. (2000) 145 2087–2103]. HIV-positive Refers to an individual who is infected with the human immunodeficiency virus (see HIV). (See also AIDS.) hives Syn. URTICARIA. Hj¨arre’s disease (coli-granuloma) A POULTRY DISEASE in which granulomatous lesions are formed in the wall of the intestine (particularly in the caecum); the causal agent is Escherichia coli. HLA-A, HLA-B etc. See MAJOR HISTOCOMPATIBILITY COMPLEX. Hly plasmid See ESCHERICHIA. HlyA (of Escherichia coli ) See RTX TOXINS. HMA Hydroxymethionine analogue: DL-a-hydroxy-g-methiolbutyrate; HMA is used in animal feedstuffs as a sulphur amino acid supplement [ARB (1983) 52 215–216]. (See also SINGLE-CELL PROTEIN.) HMG box That region, in certain types of protein, which can e.g. interact with sharply angular or kinked DNA (in eukaryotic cells); it consists of a sequence of about 80 amino acid residues (including a high proportion of aromatic amino acids) with a net positive charge. HMG boxes are found in certain NON-HISTONE PROTEINS. (See also HU PROTEIN.) HMG proteins See NON-HISTONE PROTEINS. HMP pathway HEXOSE MONOPHOSPHATE PATHWAY. HMS-1 b-lactamase See b-LACTAMASES. HMT toxin A long-chain polyketide host-specific toxin produced by Drechslera (Helminthosporium) maydis race T; it has been suggested that HMT toxin acts as an ionophore.

Attachment of the virion to a target cell. The principal high-affinity binding site for viral gp120 glycoprotein is the CD4 antigen (see CD4) (formerly referred to as OKT4); target cells for HIV therefore include the CD4+ (‘T helper’) subset of T LYMPHOCYTES, monocytes, macrophages and dendritic cells. CD4+ cells also occur in the central nervous system (microglial cells), and infection of these cells by HIV may account for neurological symptoms in HIV-positive patients; multinucleate (syncytial) cells have been observed in brain tissue from such patients. For infection of a cell by HIV, the cell must express not only CD4 antigen but also receptors for particular CHEMOKINES – e.g. those for certain CXC-type and CC-type chemokines (the CXCR4 and CCR5 receptors) [JLB (1999) 65 552–565]. Some (T-cell-tropic) strains of HIV require the co-receptor CXCR4 while other (M-tropic) strains require CCR5; M-tropic strains can infect macrophages and monocytes as well as T cells. Yet other (dual-tropic) strains of HIV can use both co-receptors. On the basis of their use of particular co-receptors, strains of HIV have been categorized as X4, R5 and R5X4 respectively. Some CD34+ haemopoietic stem cells co-express the CD4 antigen (and co-receptors) but these cells are apparently not susceptible to infection by pathogenic strains of HIV; however, such cells are susceptible to infection by genetically engineered viral ‘constructs’ (based on HIV) which may be of use in GENE THERAPY. Although stem cells may not be susceptible to natural strains of HIV, inhibition of haemopoiesis may nevertheless occur in HIV+ patients owing to perturbation of the cytokine milieu in bone marrow. [Haematological aspects of HIV infection: BCH (2000) 13 215–230.] Internalization and integration of HIV. Fusion between viral envelope and cell membrane is achieved in a gp41-dependent manner; the viral core then enters the target cell’s cytoplasm. On (intracellular) release of viral RNA and enzymes, a dsDNA form of the genome is synthesized using viral reverse transcriptase and RNase H (see: RETROVIRIDAE). [HIV entry inhibitors: PNAS (2002) 99 16249–16254.] The 3′ and 5′ LTRs of the dsDNA are involved in circularization of the molecule (forming a plasmid-like structure); this structure enters the nucleus and is integrated into the host’s genome in a process involving the viral integrase. In some cases the integrated (provirus) form of HIV remains latent (inactive), or weakly active, for some time (e.g. ∼10 years), the patient remaining essentially asymptomatic; in other cases disease progresses rapidly. Replication of HIV. Replication is apparently an inefficient process in which a high proportion of progeny virions are defective. Transcription of the integrated viral genome appears to depend on various (viral and host) regulatory proteins which have binding sites on the LTR. For example, the viral tat gene product, with a binding site designated Tat-responsive region (TAR), has an important transactivation role; the activity of this protein is essential in the upregulation of replication. The host’s nuclear transcription factor, NF-kB (see CYTOKINES), is also important as a (positive) regulator of viral gene expression and it, too, has a binding site on the LTR; it is therefore possible that expression of viral genes may be promoted by superinfection with certain opportunist pathogens that activate NF-kB by inducing synthesis of appropriate cytokines. (This suggests a possible mechanism for the exacerbation of HIV-mediated disease that may be seen during opportunist infections.) 372

homogenote hnRNA Heterogeneous nuclear RNA: the high-MWt RNA synthesized by RNA polymerase II in the nucleus of a eukaryotic cell; hnRNA occurs in the form of ribonucleoprotein (hnRNP) and includes pre-mRNA (i.e., MRNA before the generation of 3′ ends, polyadenylation and splicing). H-NS protein (syn. H1 protein) In bacteria (e.g. Escherichia coli ), a small protein (136 amino acids, 15.6 kDa) encoded by the hns gene. H-NS protein is able to (i) regulate the expression of various unrelated genes (e.g. bgl, proU ), (ii) constrain negative supercoiling, and (iii) contribute to the physical organization of the bacterial nucleoid. In uropathogenic strains of E. coli (UPEC) the H-NS protein has been implicated in the temperature-dependent expression of P FIMBRIAE: at the non-permissive temperature of 25° C, the H-NS protein is reported to act as a methylation-blocking factor, repressing transcription [Mol. Microbiol. (1998) 28 1121–1137]. In Proteus mirabilis it is reported to act as a repressor of the transcriptional activator gene, ureR, in the absence of urea induction [JB (2000) 182 2649–2653]. H-NS has also been implicated in the regulation of DNA repair in Shigella [JB (1998) 180 5260–5262]. H-NS protein is able to condense supercoiled plasmid DNA, and appears to play a major part in condensing DNA in the nucleoid. H-NS-mediated condensation of DNA has been investigated by studying the structure of H-NS–DNA complexes by atomic force microscopy [NAR (2000) 28 3504–3510]. Hoarella A genus of protozoa (suborder EIMERIORINA) which form dizoic oocysts each containing 16 sporocysts. Hoechst 33258 A bis-benzimidazole derivative: a FLUOROCHROME used e.g. for staining chromosomes. hog cholera Syn. SWINE FEVER. hog diseases See PIG DISEASES. Hogness box See PROMOTER. holdfast An organ or organelle by means of which an organism or cell attaches to the substratum or to another organism. Examples include the root-like region of LAMINARIA, and the specialized regions in SPORICHTHYA and members of the ASTOMATIDA. holding–flush jar procedure In the culture of anaerobes: a procedure which minimizes the exposure of plates to O2 ; essentially, uninoculated plates, or inoculated plates awaiting incubation, are held in an anaerobic jar (with unclamped lid) while a stream of O2 -free gas (e.g. N2 or CO2 ) is continually directed through a tube to the bottom of the jar. holin See LYSIS PROTEIN. Hollandina See SPIROCHAETALES. Holliday junction See RECOMBINATION. Holliday model See RECOMBINATION (Figure 1). Holliday structure See RECOMBINATION. Holmsella A genus of algae (division RHODOPHYTA). H. pachyderma is a colourless organism which is parasitic on the red alga Gracilaria; PIT CONNECTIONS have been observed between H. pachyderma and Gracilaria. Holobasidiomycetidae A subclass of fungi (class HYMENOMYCETES) characterized by the formation of holobasidia (see BASIDIUM). Orders [Book ref. 64, p. 189]: AGARICALES, APHYLLOPHORALES, BOLETALES, BRACHYBASIDIALES, CANTHARELLALES, DACRYMYCETALES, EXOBASIDIALES, RUSSULALES and TULASNELLALES. holobasidium See BASIDIUM. holoblastic development See CONIDIUM. holocarpic Refers to those organisms in which the entire thallus takes on a reproductive function. (cf. EUCARPIC.) holocellulose A complex of cellulose and hemicelluloses (formed e.g by the removal of lignin from lignocellulosic plant material).

holocentric (holokinetic) Refers to a chromosome in which the CENTROMERE is diffuse, being distributed along the length of the chromosome; the kinetochores are correspondingly long, and microtubules are attached along the whole length of the chromosome. holococcolith See COCCOLITH. holoenzyme A ‘whole’ enzyme – i.e., an enzyme in its complete, active form – consisting either of an apoenzyme plus PROSTHETIC GROUP or of two or more distinct protein subunits (see e.g. DNA POLYMERASE). holokinetic Syn. HOLOCENTRIC. holomictic lake A lake in which the entire water mass undergoes a complete turnover. (cf. MEROMICTIC LAKE.) holomorph (mycol.) Any fungus considered in its entirety, i.e., including all latent or expressed (sexual and/or asexual) forms and potentialities. (cf. ANAMORPH; ANA-HOLOMORPH; TELEOMORPH.) Holophrya See GYMNOSTOMATIA. holophytic nutrition Plant-type nutrition, i.e., the endogenous formation of nutrients by photosynthesis. (cf. HOLOZOIC NUTRITION.) Holospora A genus of Gram-negative bacteria which are obligate endosymbionts in the micronucleus (H. elegans, H. undulata) or the macronucleus (H. caryophila, H. obtusa) of Paramecium spp; Holospora spp do not confer a killer characteristic (cf. CAEDIBACTER). Cells: non-motile rods or filaments. Type species: H. undulata. [Book ref. 22, pp. 802–803; H. obtusa in P. caudatum (infection and maintenance): JCS (1985) 76 179–187.] Holosticha See HYPOTRICHIDA. holothallic conidium See CONIDIUM. holotoxin The form in which an exotoxin is secreted by a pathogen. After uptake by a eukaryotic cell, the holotoxin may be processed (e.g. by proteolytic cleavage) to release the active component (see e.g. DIPHTHERIA TOXIN and SHIGA TOXIN). holotrich Any of the relatively primitive ciliate protozoa previously classified in the subclass Holotrichia [JP (1964) 11 7–20] but now classified in the classes KINETOFRAGMINOPHOREA and OLIGOHYMENOPHOREA. holotype The actual specimen which an author has designated as the NOMENCLATURAL TYPE of a new taxon. holozoic nutrition Animal-type nutrition, i.e., nutrition involving the ingestion of other organisms or components of other organisms. (cf. HOLOPHYTIC NUTRITION.) homing (intron, bacterial) See INTRON HOMING. homing-associated cell adhesion molecule Syn. CD44. homoacetate fermentation See ACETOGENESIS. homocaryon Syn. HOMOKARYON. homocysteine See e.g. Appendix IV(d). homocytotropic antibodies (1) Syn. REAGINIC ANTIBODIES. (2) Antibodies which bind only to cells of the species in which they were formed. (cf. HETEROCYTOTROPIC ANTIBODIES.) homodiaphoromixis See HOMOTHALLISM. homodimixis See HOMOTHALLISM. homoduplex Any double-stranded nucleic acid in which each strand is completely complementary to the other. (cf. HETERODUPLEX.) homoeomerous Syn. HOMOIOMEROUS. homofermentation (1) Any fermentation in which there is only one major end-product. (2) Syn. HOMOLACTIC FERMENTATION. homogeneous immersion See IMMERSION OIL. homogenization (of milk) See MILK. homogenote See MEROZYGOTE. 373

homoglycan homoglycan See POLYSACCHARIDE. homoheteromixis See HOMOTHALLISM. homoimmune phages See SUPERINFECTION IMMUNITY. homoiomerous (homoeomerous) (1) (lichenol.) Refers to a lichen thallus in which the photobiont is more or less evenly distributed throughout the thallus (see LICHEN). (2) (mycol.) In an agaric: refers to a pileus or stipe composed of hyphae only. (3) (ciliate protozool.) See MACRONUCLEUS. (cf. HETEROMEROUS.) homoisocitrate pathway See icl− SERINE PATHWAY. homokaryon (homocaryon) (mycol.) A hyphal cell, mycelium, organism or spore in which all the nuclei are genetically identical. (cf. HETEROKARYON.) homokaryotic (1) (mycol.) Refers to a HOMOKARYON. (2) (ciliate protozool.) Having only one type of nucleus: see PRIMOCILIATID GYMNOSTOMES. homolactic fermentation A type of LACTIC ACID FERMENTATION in which e.g. glucose is converted entirely, or almost entirely, to lactic acid. Many LACTIC ACID BACTERIA (e.g. Lactococcus lactis, thermobacteria and streptobacteria) carry out a homolactic fermentation of glucose (or lactose) under conditions of glucose (or lactose) excess (cf. LACTIC ACID STARTERS); glucose is metabolized by the EMBDEN–MEYERHOF–PARNAS PATHWAY, and most or all of the pyruvate thus formed is converted to lactic acid. (See also LACTOSE.) However, under glucose or lactose limitation, or with different substrates (e.g. PENTOSES), the same organisms may form other products, sometimes with little or no lactic acid; for example, many strains of L. lactis produce mainly formic and acetic acids and ethanol when grown in glucose- or lactose-limited continuous culture (see Appendix III(c)). (See also DIACETYL.) homologous (1) Similar in form or structure, but not necessarily in function; homology suggests evolutionary relatedness. (2) Derived from or associated with the same species as that being referred to. (cf. HETEROLOGOUS (1).) (3) See ALTERNATION OF GENERATIONS. (4) (immunol.) The antibody elicited by a given antigen is said to be homologous to that antigen; similarly, the antigen is said to be homologous to the antibody. (cf. HETEROLOGOUS (3).) (5) (genetics) Of chromosomes or chromatids: containing the same sequence of genes – but not necessarily identical alleles. (6) (genetics) Of nucleic acids: see e.g. DNA HOMOLOGY. homologous interference See INTERFERENCE (1). homologous recombination See RECOMBINATION. homologue (of chromosomes) In a diploid eukaryotic nucleus: each of a pair of CHROMOSOMES which encode the same types of characteristics and which are usually morphologically similar; in general, homologous chromosomes carry the same sequences of genes, though not necessarily the same alleles. homology (of DNA) See DNA HOMOLOGY. homomixis See HOMOTHALLISM. homonym Any name used to refer to each of two (or more) different microbial taxa; a name of a higher animal or plant which is identical to that of a microorganism is not considered to be a homonym. The name published first is the senior homonym, while any name published later is a junior homonym; junior homonyms are usually suppressed. homophilic binding (of cell adhesion molecules) See IMMUNOGLOBULIN SUPERFAMILY. homoplasmid segregant See INCOMPATIBILITY. homopolymer tailing See TAILING. homopolysaccharide See POLYSACCHARIDE. homoserine See e.g. Appendix IV(d). homothallism (homomixis) Self-fertility: the phenomenon in which sexual reproduction can involve the fusion of e.g. gametes

derived from the same individual (as well as the fusion of those derived from different individuals); no ‘mating types’ are involved (cf. HETEROTHALLISM). Secondary homothallism (= homoheteromixis) occurs in some fungi which are basically heterothallic; it can arise e.g. when nuclei of compatible mating types are incorporated in the same spore – the thallus developing from such a spore being selffertile. (This occurs regularly in e.g. Neurospora tetrasperma.) If secondary homothallism involves nuclei whose compatibility is determined on a one-locus two-allele basis the phenomenon is called homodimixis; if it is determined on a one- or two-locus multi-allele basis the phenomenon is called homodiaphoromixis. homothetogenic Refers to the type of cell division typical of ciliate protozoa: transverse (PERKINETAL) BINARY FISSION in which the daughter cells (the PROTER and OPISTHE) are not mirror images of one another – although they may be similar or identical. For example, when Tetrahymena divides, the anterior end of the opisthe is near the plane of division. (cf. SYMMETROGENIC; see also INTERKINETAL.) homoxenous (monoxenous, autoecious) Refers to a parasite which completes its life cycle in a single host species. (cf. HETEROXENOUS.) homozygote A HOMOZYGOUS cell or organism. homozygous Refers to a cell or organism (e.g. a diploid eukaryote or a bacterial MEROZYGOTE) in which one or more specified genes, or all of the genes, are present in the form of identical ALLELES. (cf. HETEROZYGOUS.) honey-bee diseases See BEE DISEASES. honey fungus See ARMILLARIA. honeydew A sugary secretion produced e.g. by sap-sucking insects such as aphids. Sap-sucking insects feed on phloem sap which is rich in sugars but low in nitrogen; thus, large quantities of sap must be ingested to satisfy the insect’s nitrogen requirements, the excess sugars being excreted as honeydew. Insect honeydews vary in composition (depending e.g. on insect); some contain e.g. melezitose (rare in nature), and some are rich in polyols (galactitol, ribitol, etc). Certain fungi – particularly SOOTY MOULDS – may grow abundantly on insect honeydews, and it has been suggested that honeydews falling on soil below insect-infested plants may enhance nitrogen-fixation by freeliving bacteria in the soil [SBB (1984) 16 203–206]. (See also CLAVICEPS.) Hong Kong flu See INFLUENZAVIRUS. Hoogsteen hydrogen bonding See TRIPLEX DNA. hook (flagellar) See FLAGELLUM (a). hop latent virus See CARLAVIRUSES. hop mosaic virus A member of the CARLAVIRUSES which can cause severe to lethal disease in certain (Golding-type) cultivars of hops (Humulus lupulus); symptoms include chlorotic veinbanding, curling of leaf-margins, stunting etc. Transmission occurs via aphids. Weeds (e.g. Urticaria urens, Chenopodium album, Plantago major ) may be important reservoirs of the virus. Sensitive hop cultivars have been replaced by tolerant cultivars in endemic areas. Hop protein (plant pathol.) Hrp-dependent outer protein: a proposed designation for proteins secreted via the Hrp system (see AVIRULENCE GENE) – some of which may lack an avirulence function (and are therefore inappropriately referred to as avr proteins) [JB (1997) 179 5655–5662 (5659–5660)]. hop stunt viroid See VIROID. hopanes See bacterial CYTOPLASMIC MEMBRANE. HOQNO HYDROXYQUINOLINE-N-OXIDE. hordeiviruses (barley stripe mosaic virus group) A group of multicomponent PLANT VIRUSES in which the virions are elongated, 374

hot–cold lysis hormone A See PHEROMONE. hormone B See PHEROMONE. horse diseases Horses may be affected by a wide range of diseases, some of which are specific to equines. (a) Bacterial diseases: see e.g. CONTAGIOUS EQUINE METRITIS; CONTAGIOUS PUSTULAR DERMATITIS (sense 2); GLANDERS; PARATYPHOID FEVER; POTOMAC HORSE FEVER; SLEEPY FOAL DISEASE; STRANGLES; TULARAEMIA; TYZZER’S DISEASE; ULCERATIVE LYMPHANGITIS. (See also RHODOCOCCUS (R. equi ).) (b) Fungal diseases: see e.g. ASPERGILLOSIS; EPIZOOTIC LYMPHANGITIS; EQUINE PHYCOMYCOSIS; SPOROTRICHOSIS. (See also PASPALUM STAGGERS and PENITREMS.) (c) Protozoal diseases: see e.g. DOURINE; EQUINE PROTOZOAL MYELOENCEPHALITIS; SURRA. (d) Viral diseases: see e.g. AFRICAN HORSE SICKNESS; BORNA DISEASE; EASTERN EQUINE ENCEPHALOMYELITIS; EQUINE COITAL EXANTHEMA; SWAMP FEVER (equine infectious anaemia); VENEZUELAN EQUINE ENCEPHALOMYELITIS; VESICULAR STOMATITIS; WESTERN EQUINE ENCEPHALOMYELITIS. horse mushroom See AGARICUS. horse sickness fever See AFRICAN HORSE SICKNESS. horseradish peroxidase A haemin-containing PEROXIDASE, used e.g. in the IMMUNOPEROXIDASE METHODS. host-controlled modification The modification of bacteriophage DNA by its host’s modification enzymes (see RESTRICTION – MODIFICATION SYSTEM). If a given phage replicates in a particular bacterial strain, the DNA of the progeny phages will carry the modification pattern characteristic of that strain; such phages will be able to infect other cells of the same strain with high efficiency. If these phages infect another strain of bacteria in which there is a different R-M system, a low efficiency of plating is generally observed since, in most of the cells, infection is followed by restriction of the phage DNA; however, in a few cells restriction may fail to occur, and the phage DNA then acquires the modification pattern characteristic of the new strain. The modified DNA can replicate, the daughter strands being modified by the host enzymes; the progeny phages can efficiently infect cultures of the new strain, but will infect cultures of the original strain with low efficiency. host-dependent mutant A CONDITIONAL LETHAL MUTANT bacteriophage which contains e.g. an amber mutation in an essential gene and can thus replicate only in a (permissive) host which contains an intergenic amber SUPPRESSOR MUTATION. host-range mutant (h mutant; hr mutant) A mutant virus in which the mutation alters the host range of the virus (i.e. the type(s) of cell which it can infect). hot-air oven An apparatus used for the dry-heat STERILIZATION of e.g. clean glassware and those materials (such as mineral oils) which cannot be sterilized in an AUTOCLAVE owing to their impermeability to steam. It consists of an electrically heated, thermostatically controlled, heat-insulated cabinet which, ideally, incorporates an internal fan to prevent temperature stratification. Typical sterilizing conditions are 160–170° C/1 hour. hot–cold lysis A phenomenon in which incubation of susceptible red blood cells (RBCs) with e.g. staphylococcal b-HAEMOLYSIN at 37° C causes little or no haemolysis, but subsequent chilling to 0–4° C causes rapid and extensive haemolysis. The sensitivity of RBCs from different species depends on the SPHINGOMYELIN content of their membranes, those from sheep, goat and ox being the most sensitive. Hot–cold lysis is still not fully understood; it may reflect the combined effects of degradation of sphingomyelin in the outer leaflet of the cell membrane (with consequent condensation of the resulting ceramide into droplets in the outer layer) and the weakening of hydrophobic forces

rigid particles (ca. 100–150 × 20 nm) composed of ssRNA and helically-arranged subunits of a single type of coat protein (MWt ca. 21000). The genome appears to consist of 2–4 molecules (depending on strain) of linear positive-sense ssRNA, two or three of which are necessary for infection. The 3′ end of the RNA has an internal poly(A) sequence and a 3′ -terminal tRNAlike structure which can be amino-acylated with tyrosine in vitro [Virol. (1982) 119 51–58]. Viruses accumulate mainly in the cytoplasm but also in the nuclei of infected cells. Type member: barley stripe mosaic virus (BSMV), an important pathogen of barley in many regions of the world; some strains of BSMV can also infect wheat, oats etc. Transmission is mechanical and seed-borne. Seeds from BSMV-infected plants may show increased frequencies of triploidy and aneuploidy, and some BSMV strains induce a heritable genetic anomaly (‘aberrant ratio phenomenon’ [ARPpath (1984) 22 77–94]) characterized by abnormal segregation ratios for one or more genetic markers. hordeolum Syn. STYE. horizontal resistance (plant pathol.) In a given cultivar: the existence of similar levels of resistance to each of the races of a given pathogen. Unlike VERTICAL RESISTANCE, horizontal resistance tends to be a permanent (though not necessarily complete) form of resistance which does not readily break down when genetic changes occur in the pathogen; it is commonly inherited polygenically. horizontal transmission (lateral transmission) Transmission of a disease or parasite from one individual to another contemporary individual. (cf. VERTICAL TRANSMISSION.) Hormidium Syn. KLEBSORMIDIUM. Hormiscium dermatitidis See WANGIELLA. Hormoconis A genus of fungi of the HYPHOMYCETES. H. resinae (formerly Cladosporium resinae, the ‘creosote fungus’ or ‘kerosene fungus’) can utilize e.g. creosote and various hydrocarbons as sources of carbon (see also PETROLEUM). [Mechanism of dodecane uptake by H. resinae: JGM (1986) 132 751–756.] The teleomorph of H. resinae is the ascomycete Amorphotheca resinae. [Discussion and references on re-naming of C. resinae: MS (1986) 3 169.] hormocyst In certain cyanobacteria: short filaments – composed of granular cells surrounded by a common, condensed sheath – formed in intercalary or terminal positions in the vegetative trichome; hormocysts become detached from the parent trichome and appear to function as propagules (cf. AKINETE and HORMOGONIUM). (See also LEMPHOLEMMA.) Hormodendrum dermatitidis See WANGIELLA. Hormodendrum resinae Syn. Hormoconis resinae. hormogonium A short filament of undifferentiated cells (i.e., lacking heterocysts or akinetes) formed by filamentous CYANOBACTERIA (members of sections III, IV and V) and by e.g. Beggiatoa; hormogonia may be formed by the fragmentation of whole filaments (e.g. in Oscillatoria and Cylindrospermum) or may develop from the tips of trichomes (e.g. in Scytonema). (See also NECRIDIUM.) Hormogonia may differ from the parent trichome e.g. in having smaller cells; they are typically motile (by gliding) and usually move some distance before developing into mature filaments, thus functioning as propagules. In some cyanobacteria (e.g. Nostoc muscorum [JGM (1983) 129 263–270], Calothrix spp), GAS VACUOLES are formed only in the hormogonia, the increased buoyancy they confer presumably aiding in the dispersal of the hormogonia. hormone A substance which is released from specialized cells in specific part(s) of a multicellular organism and which, in small quantities, can bring about one or more specific responses when translocated to other part(s) of the same individual. 375

hot-spot on cooling [Book ref. 44, pp. 721–725]. Hot–cold lysis with staphylococcal b-toxin is most easily demonstrated in the testtube; blood agar plates may give less consistent results. Hot–cold lysis can also occur with the a-toxin of Clostridium perfringens. hot-spot (mol. biol.) A region of DNA which is particularly prone to e.g. transposition (see TRANSPOSABLE ELEMENT) or mutation (see SPONTANEOUS MUTATION). hot-start PCR A form of PCR in which an essential component of the reaction mixture is withheld, or blocked, until the temperature of the mixture has, for the first time, risen above the primer-binding temperature; the object of this procedure is to avoid mis-priming (i.e. binding of primers to inappropriate sequences) – which, in the standard form of PCR, tends to occur primarily in the initial pre-cycling stage, i.e. when all components are present but the mixture is still at room temperature. By avoidance (or minimization) of mis-priming, the hot-start technique promotes the specificity of a PCR assay; it can also promote the sensitivity of an assay by concentrating the full potential of the system on amplification of the required target sequence. Avoidance or minimization of non-specific products also serves to reduce the background against which the legitimate target is to be detected. In one commercial procedure, a chemically modified form of the polymerase (AmpliTaq Gold DNA polymerase; PerkinElmer) is initially inactive (when added to the reaction mixture) but is thermally activated at 95° C when the temperature first rises to the denaturation level. In another commercial system, the reaction mixture is prepared with all components except the polymerase; a layer of molten wax (AmpliWax ; Perkin-Elmer) is allowed to set on the surface of the mixture, and the polymerase is then added above the wax barrier. Once cycling begins, the wax melts when the temperature first exceeds ∼75–80° C; the reactants then mix, and PCR proceeds normally. [See also Nature (1996) 381 445–446.] housefly virus (HFV) A virus pathogenic in the housefly (Musca domestica); it resembles viruses of the REOVIRIDAE in having a dsRNA genome (10 genes), but is apparently not serologically related to reoviruses. [Book ref. 83, p 5.] Howell–Jolly body In some erythrocytes in a stained blood smear: a small, dark, rounded body generally considered to be a fragment of the precursor cell’s disintegrating nucleus. Hoyer’s medium (Frateur’s modification) A medium in which ethanol is the sole source of carbon, and (NH4 )2 SO4 the sole source of nitrogen; it includes K2 HPO4 , KH2 PO4 , MgSO4 , FeCl3 , biotin, calcium pantothenate, thiamine, folic acid, PABA, vitamin B12 , pyridoxal-HCl, niacin and riboflavin. (See e.g. ACETOBACTER.) HpaI A RESTRICTION ENDONUCLEASE from Haemophilus parainfluenzae; GTT/AAC. HpaII A RESTRICTION ENDONUCLEASE from Haemophilus parainfluenzae; C/CGG. HPI layer See DEINOCOCCUS. HPLC High-pressure liquid CHROMATOGRAPHY. HPr See PTS. HPr kinase See CATABOLITE REPRESSION. hprK gene (in Staphylococcus xylosus) See CATABOLITE REPRESSION. HPUra (Hpura) 6-(p-Hydroxyphenylazo)uracil: an inhibitor of DNA polymerase III in e.g. Gram-positive bacteria. HPV Human papillomavirus – see PAPILLOMA and PAPILLOMAVIRUS. (Note. ‘Human parvovirus’ was formerly referred to as HPV

but is now referred to as ‘parvovirus B19’ or ‘B19 parvovirus’ (see ERYTHROVIRUS).) HQNO HYDROXYQUINOLINE-N-OXIDE. hr mutant HOST-RANGE MUTANT. HR756 Syn. cefotaxime (see CEPHALOSPORINS). Hrp secretion pathway (plant pathol.) See AVIRULENCE GENE. HRP-2 protein See MALARIA. HS HAEMOPHAGOCYTIC SYNDROME. HSA (serol.) Human serum albumin. hsp genes Genes encoding HEAT-SHOCK PROTEINS. HSV HERPES SIMPLEX virus. HT-2 toxin See TRICHOTHECENES. HTF Mastigocladus See CHLOROGLOEOPSIS. HTLV Human T-lymphotropic virus (= human T-cell leukaemia virus, human T-cell leukaemia/lymphoma virus): a generic term for exogenous, replication-competent human retroviruses (see RETROVIRIDAE) which (at least HTLV-I and HTLV-II) can infect and transform CD4+ T LYMPHOCYTES; other types of cell (including macrophages) can also be infected. HTLV-I (formerly ‘HTLV’) was first identified in the neoplastic T cells of patients with ADULT T CELL LEUKAEMIA (ATL) and is now regarded as a causal agent of that disease; this virus has also been associated with some non-malignant diseases which include spastic paraparesis and uveitis. Infection with HTLV-I is permanent (i.e. life-long). A carrier state is recognized. Transmission of the virus appears to occur mainly via breast-feeding, sexual contact and blood transfusion. Endemic areas include Japan, the Caribbean, parts of Africa and Latin America. The virion of HTLV-I is ∼75 µm in diameter. The genome of HTLV-I integrates at random sites in the host’s DNA; transformed T cells from ATL patients contain only one, or a few, copies of the viral genome per cell. The genome of HTLV-I (∼9–10 kb) includes the genes gag, pol and env (analogous to those of other retroviruses). A further gene, pro, encodes a protease. Near the 3′ end of the genome (the pX region) are several genes that include rex and tax, both of which are involved in viral replication. The genome lacks a viral oncogene. In addition to its role in viral replication, the Tax protein induces the expression of a number of host genes – including that encoding INTERLEUKIN-2 and the ONCOGENE c-fos. Expression of such host proteins may promote leukaemogenesis. (In vitro, HTLV-I is reported to transform normal human peripheral blood T cells, the transformed cells continuing to proliferate in the absence of exogenous interleukin-2.) HTLV-I is closely related to SIMIAN T-CELL LEUKAEMIA VIRUS (strains of which are >85% homologous with HTLV-I in terms of nucleotide sequence); it is also related to bovine leukosis virus (BLV). HTLV-II has been rarely isolated – initially from a T cell line derived from a case of (T cell) HAIRY CELL LEUKAEMIA [Science (1982) 218 571–573]. The nucleotide sequence of HTLV-II is 70% homologous with that of HTLV-I. The pathogenic potential of HTLV-II is uncertain, although one report described a patient with disease closely resembling HTLV-I-associated myelopathy in a patient infected with HTLV-II. ‘HTLV-III’ was a former name for the human immunodeficiency virus (HIV). Another human T-cell lymphotropic retrovirus – related to but distinct from other HTLVs – was detected in some cases of MULTIPLE SCLEROSIS (MS), but an aetiological role (if any) for such a virus in MS has yet to be determined [Nature (1985) 318 154–160]. 376

hybridization Hungate technique See ROLL-TUBE TECHNIQUE. Hungate tube A gas-tight, tube-shaped glass vessel with a rubber stopper which is held in place by a screw cap; it is used in the ROLL-TUBE TECHNIQUE. hupA, hupB genes In Escherichia coli, the genes which encode the two subunits of the HU PROTEIN. Huroniospora See STROMATOLITES. HUS See HAEMOLYTIC URAEMIC SYNDROME. hut genes Genes involved in histidine utilization (see HISTIDINE DEGRADATION). Hutchinson’s teeth See SYPHILIS. HUVEC Human umbilical vascular endothelial cell. HVR-1 (in hepatitis C virus) See HEPATITIS C VIRUS. hyaline Transparent, translucent, or colourless. hyaline cap See PSEUDOPODIUM. hyalodendrins See EPIPOLYTHIAPIPERAZINEDIONES. hyalodidymae See SACCARDOAN SYSTEM. hyaloplasm (1) Syn. CYTOSOL. (2) See SARCODINA. Hyalospora See UREDINIOMYCETES and AMPHISPORE. Hyalotheca A genus of filamentous placoderm DESMIDS. The filaments are composed of chains of cylindrical, flat-ended cells; each cell has only a slight median constriction. hyaluronan Syn. HYALURONIC ACID. hyaluronate lyase (‘spreading factor’; EC 4.2.2.1) A LYASE which cleaves HYALURONIC ACID at the (1 → 4)-b-linkages; the end product is a disaccharide containing a 4,5-unsaturated uronic acid residue. (cf. HYALURONIDASE). It is produced e.g. by most coagulase +ve staphylococci, Streptococcus pneumoniae, S. pyogenes and Clostridium perfringens (µ toxin); it may promote invasiveness. It can be assayed by its ability to reduce viscosity in a solution of hyalauronic acid. [Action of enzyme from S. pneumoniae: EMBO (2000) 19 1228–1240.] hyaluronic acid A linear polysaccharide in which repeating disaccharide units of b-D-glucuronopyranosyl-(1 → 3)-N-acetyl-Dglucosamine are connected by (1 → 4)-b-linkages. Hyaluronic acid occurs e.g. as an intercellular constituent of various animal tissues, in synovial fluid, and in the capsules of certain group A streptococci. Hyaluronic acid forms highly viscous solutions in water and readily forms gels. hyaluronidase Any enzyme which cleaves HYALURONIC ACID; they include HYDROLASES and LYASES. The hydrolases include hyaluronate 4-glucanhydrolase (EC 3.2.1.35) – present e.g. in testicular extracts and produced e.g. by certain streptomycetes. The name ‘hyaluronidase’ is often used (erroneously) as a synonym for the enzyme HYALURONATE LYASE. hybrid antibody See CONJUGATION (2). hybrid-arrested translation A method for identifying a protein encoded by a given cDNA. mRNAs from the cell are translated in the presence of cloned, single-stranded copies of the cDNA. mRNAs which do not bind cDNA yield proteins incorporating a labelled amino acid. Translation is repeated without cDNAs, allowing translation of the mRNA previously blocked by hybridization to cDNA. The protein of interest is the extra protein formed in the second translation. hybrid plasmid (1) Any recombinant PLASMID (see e.g. CLONING). (2) A recombinant plasmid containing sequences derived from organisms which can normally exchange genetic information. (cf. CHIMERIC PLASMID.) hybridization (1) The formation of a double-stranded nucleic acid by base-pairing between single-stranded nucleic acids derived (usually) from different sources; some authors use the term specifically for the association of ssRNA with ssDNA. (See also DNA HOMOLOGY and SOUTHERN HYBRIDIZATION.)

[Early review (HTLV-I -II -III): Nature (1985) 317 395–403. Human T-cell leukaemia virus: BCH (1995) 8 131–148. Detection of HTLV-I and HTLV-II by multiplex PCR: PNAS (1999) 96 6394–6399. Human T-lymphotropic virus type I infection: BCH (2000) 13 231–243.] htpR gene See HEAT-SHOCK PROTEINS. HTST See APPERTIZATION and PASTEURIZATION. HU HYDROXYUREA. HU protein A small, basic protein, abundant in Escherichia coli, which binds strongly to angular/kinked dsDNA and which can inhibit cruciform extrusion from PALINDROMIC SEQUENCES in vitro. It functions e.g. in replication from oriC in E. coli, in some SITE-SPECIFIC RECOMBINATION systems, and in Tn10 transposition. It resembles mammalian HMG1 protein (whose DNA-binding is more structure- than sequence-dependent) [Mol. Microbiol. (1993) 7 343–350]. The HU protein is reported to be involved in regulating the expression of gene rpoS (encoding SIGMA FACTOR sS ) [Mol. Microbiol. (2001) 39 1069–1079]. Hucker’s method See GRAM STAIN. Huffia A subgenus of PLASMODIUM. Hugh and Leifson’s test OXIDATION–FERMENTATION TEST. Hughes press An apparatus for CELL DISRUPTION. A frozen suspension or paste of cells in a cylinder is forced by hydraulic pressure (up to ca. 30 tons/inch2 , i.e., ca. 480 MPa) through a small hole in the containing vessel; as the cells emerge they are broken by the solid shear forces due to the presence of intracellular ice crystals. The frozen sample may incorporate an abrasive (e.g. finely powdered glass) for more efficient cell breakage. Huilia See LECIDEA. hulle ¨ cell See EMERICELLA. human (alpha) herpesviruses See ALPHAHERPESVIRINAE. human (beta) herpesviruses See BETAHERPESVIRINAE. human caliciviruses See SMALL ROUND STRUCTURED VIRUSES. human coronavirus See CORONAVIRIDAE. human cytomegalovirus See BETAHERPESVIRINAE. human diploid cell vaccine (HDCV) See RABIES. human enteric coronavirus See CORONAVIRIDAE. human foamy viruses See SPUMAVIRINAE. human (gamma) herpesviruses See GAMMAHERPESVIRINAE. human genome (sequence) See GENOME. human herpesvirus (HHV) Any virus of the family HERPESVIRIDAE which can infect humans; HHVs occur in each of the three subfamilies ALPHAHERPESVIRINAE, BETAHERPESVIRINAE and GAMMAHERPESVIRINAE. (See also HHV.) human immunodeficiency virus See HIV. human papilloma virus See PAPILLOMAVIRUS. human parvovirus See PARVOVIRUS. human T-cell leukaemia/lymphoma virus See HTLV. human T-lymphotropic virus See HTLV. Humicola See HYPHOMYCETES; see also COMPOSTING and SOFT ROT (sense 1). humicolous Growing in or on soil or humus. humoral antibodies Antibodies present (free) in plasma and in other body fluids. humoral immunity (1) ANTIBODY-dependent IMMUNITY; humoral immunity can be transferred to a non-immune individual by the transfer of cell-free plasma or serum. (cf. CELL-MEDIATED IMMUNITY; see also IMMUNIZATION (sense 1); ADCC; JONES–MOTE SENSITIVITY.) (2) Immunity derived from any factor(s) in the body fluids – e.g. antibodies, LYSOZYME, COMPLEMENT. humus tank See SEWAGE TREATMENT. 377

hybridization protection assay hydrocarbons Compounds which contain only carbon and hydrogen; they occur e.g. in PETROLEUM. Many types of hydrocarbon can be used as substrates for growth by various microorganisms. Such organisms are ecologically important e.g. in the degradation of petroleum pollutants, and some may be commercially useful e.g. in the production of SINGLE-CELL PROTEIN from hydrocarbons; however, certain hydrocarbon-utilizing organisms can cause spoilage of hydrocarbon products such as fuels (see PETROLEUM). Hydrocarbon metabolism is strictly aerobic and appears always to involve the introduction of oxygen into the molecule in a process requiring a monooxygenase (= hydroxylase) or dioxygenase (see OXYGENASE). Aliphatic hydrocarbons. Straight-chain paraffins (n-alkanes) can be utilized by bacteria (e.g. strains of Acinetobacter, Corynebacterium, Mycobacterium, Nocardia, Pseudomonas), by yeasts (e.g. species of Candida), and by mycelial fungi (e.g. species of Aspergillus, Botrytis, Fusarium, Helminthosporium, Hormoconis, Penicillium). Some organisms can use only shortchain alkanes, some can use only long-chain alkanes. In most cases n-alkane metabolism appears to occur by !-oxidation, i.e., a terminal methyl group of the alkane is oxidized by a monooxygenase to form a primary alcohol which is in turn (apparently) oxidized, via the aldehyde, to the corresponding fatty acid by alcohol dehydrogenase and aldehyde dehydrogenase activities; the fatty acid can then be degraded by conventional b-oxidation. In e.g. Pseudomonas strains the alkane-oxidizing enzyme system is complex, involving an !-monooxygenase, a rubredoxin (see IRON–SULPHUR PROTEINS), and an NADH-rubredoxin oxidoreductase; in eukaryotes, and possibly in certain bacteria (e.g. Acinetobacter strains [FEMS (1981) 11 309–312]), the alkane monooxygenase is linked to the cytochrome P-450 electroncarrier system (see CYTOCHROMES). (See also METHANOTROPHY.) In some organisms an alkane may be oxidized at both ends, resulting in the formation of a dicarboxylic acid. Subterminal oxidation may also occur. Branched-chain alkanes (alkylalkanes) and unsaturated hydrocarbons (alkenes, olefins) are generally somewhat less susceptible to microbial degradation than are n-alkanes; they may be oxidized in the same way as n-alkanes, but alkenes may also be oxidized at the double bond, resulting in the formation of a diol. Organisms growing on alkanes have certain characteristic structural features. For example, yeasts growing on hydrocarbons generally contain numerous PEROXISOMES which are apparently involved in fatty acid metabolism rather than in alkane oxidation per se. Alkane-utilizing bacteria generally contain intracytoplasmic membranes together with ‘hydrocarbon inclusions’: electron-translucent, spherical bodies (ca. 0.2 µm diam.) limited by a non-unit-type (monolayer) membrane; the inclusions occur at the cell periphery or in close association with the intracytoplasmic membranes, and apparently contain unmodified alkane, protein, phospholipid and neutral lipid. Since alkane metabolism occurs intracellularly, the hydrocarbon must be taken into the cell. Uptake may occur by different mechanisms in different organisms, and in at least some cases may require prior emulsification of the hydrocarbon by an extracellular BIOSURFACTANT or bioemulsifier. Alicyclic hydrocarbons (cycloparaffins, cycloalkanes) are cyclic, non-aromatic hydrocarbons; they are generally less susceptible to microbial attack than either aliphatic or aromatic compounds. A suggested pathway for the degradation of e.g. cyclohexane by strains of Nocardia or Pseudomonas involves oxidation of the cyclohexane to cyclohexanol by a cyclohexane monooxygenase; cyclohexanol is oxidized to cyclohexanone,

(2) The formation of e.g. a HYBRID PLASMID. (3) The formation of a hybrid cell (see e.g. HYBRIDOMA), or of a hybrid organism (e.g. by a cross between genetically dissimilar organisms). hybridization protection assay See TMA. hybridoma The product and/or progeny of cell fusion (‘somatic cell hybridization’) between a tumour cell and a non-tumour cell; the in vitro production of hybridomas is carried out to provide continuously replicating (hybrid) cells which exhibit some or all of the characteristics of the non-tumour cell. Hybridomas have been formed, for example, between normal B LYMPHOCYTES and MYELOMA cells; such hybridomas are used e.g. as sources of MONOCLONAL ANTIBODIES. In one method of B cell hybridoma formation, spleen (or lymph node) cells are mixed with similar numbers of myeloma cells and centrifuged. The cell pellet is briefly exposed to polyethylene glycol (PEG) which promotes cell fusion. (Lysolecithin or inactivated Sendai virus has been used in place of PEG.) (cf. ELECTROFUSION.) The PEG is diluted out, and the fusion mixture is then centrifuged; the pellet is re-suspended in a growth medium, divided into aliquots, and incubated. Small cluster(s) of hybridoma cells appear in the aliquots after ca. 1 week. (The number of hybridomas depends e.g. on the initial cell density: the fusion rate may be e.g. 1 in 104 .) In order to prevent the culture from being overgrown by the myeloma cells, use is made of (pre-selected) mutant myeloma cells which are blocked in one of their two (normal) pathways for nucleotide synthesis; such mutants lack either thymidine kinase (TK− mutants) or hypoxanthine-guaninephosphoribosyltransferase (HGPRT− mutants) so that they cannot use the ancillary (‘salvage’) pathway for nucleotide synthesis and (hence) cannot use exogenous thymidine or hypoxanthine (or guanine). Accordingly, to suppress the growth of non-fused myeloma cells, the fusion mixture is incubated in a medium (HAT medium) which contains aminopterin (a folic acid analogue which blocks the main pathway of nucleotide synthesis) together with hypoxanthine and thymidine; thus, the main pathway for nucleotide synthesis is blocked in both myeloma and non-myeloma cells, while fused (hybridoma-forming) myeloma cells can continue to grow by using TK or HGPRT supplied by their non-mutant partner cells. In order to prevent the formation of hybrid Ig (molecules which contain heavy and/or light chains from each of both partner cells), use is made of mutant myeloma cells which do not secrete Ig components. Activated or proliferating B cells fuse to myeloma cells more readily than do quiescent B cells; hence, prior to hybridoma formation, B cells of the required antibody specificity should be activated e.g. by antigenic challenge. (The consequent expansion of particular B cell clone(s) will also increase the incidence with which the cells of such clones participate in hybridoma formation.) T cell hybridomas have been used e.g. in the study of cytokines, and for characterization of the different T LYMPHOCYTE subsets. Hydnaceae See APHYLLOPHORALES. Hydnum See APHYLLOPHORALES (Hydnaceae). Hydra viridis See ZOOCHLORELLAE. Hydramoeba A genus of amoebae (order AMOEBIDA) which occur both free-living and as parasites in the gastrodermis of Hydra sp. hydrocarbon inclusions See HYDROCARBONS. 378

hydrogen swell hydrogen peroxide (a) (as an antimicrobial agent) Hydrogen peroxide (H2 O2 ) is an OXIDIZING AGENT which can be an effective disinfectant at low concentrations (e.g. 0.1% or less) and can act as a sterilant (for inanimate objects) at high concentrations (e.g. 10–25%); sporicidal activity at high concentrations is enhanced by ultrasonic energy and by certain metal ions, particularly Cu2+ . Dilute aqueous solutions of H2 O2 are used for the treatment of wounds; here, antimicrobial activity may be largely mechanical – tissue CATALASE causing a rapid evolution of oxygen which can dislodge contaminating foreign matter, thus facilitating its removal. However, the strongly oxygenated environment thus created in the wound can inhibit the development of anaerobic pathogens. The antimicrobial action of H2 O2 may be due to its reduction to the highly reactive HYDROXYL RADICAL which can react e.g. with membrane lipids and nucleic acids. [Book ref. 65, pp. 240–244.] Escherichia coli and Salmonella typhimurium, when exposed to sublethal concentrations of H2 O2 , acquire resistance to higher doses of H2 O2 and other oxidants; in S. typhimurium this ‘adaptation’ to oxidative stress involves the induction of various proteins, some of which are apparently encoded by a regulon under the positive control of a locus designated oxyR [Cell (1985) 41 753–762]. [Toxicity, mutagenesis and stress responses induced in E. coli by H2 O2 : JCS (1987) Supplement 6 289–301.] Peracids (acids containing the peroxy group, −O−O−) – which can be regarded as derivatives of H2 O2 – are oxidizing agents whose activity is greater than that of H2 O2 . Peracetic acid (CH3 .COO.OH) is the most active antimicrobial agent of the organic peracids, and can act as a sterilant at quite low concentrations (e.g. 1% or less). An aqueous solution of sodium perborate (NaBO3 ) acts as a mixture of borate and hydrogen peroxide; a paste of sodium perborate in water or glycerol has been used for the treatment of oral infections involving anaerobes (e.g. Vincent’s angina). [H2 O2 and peracetic acid as antimicrobial agents: JAB (1983) 54 417–423.] (b) (as a metabolite) H2 O2 is produced e.g. by the spontaneous or enzymatic dismutation of SUPEROXIDE (see also SUPEROXIDE DISMUTASE). Endogenously formed H2 O2 may be inactivated, intracellularly, by e.g. CATALASE or GLUTATHIONE PEROXIDASE, thus preventing the toxic effects of H2 O2 (H2 O2 can inactivate some types of superoxide dismutase, and can give rise to HYDROXYL RADICAL and SINGLET OXYGEN). However, extracellular H2 O2 , produced by the activities of certain organisms, may be important e.g. in LIGNIN degradation and in BROWN ROT (sense 1). (See also DIANISIDINE and LACTOPEROXIDASE–THIOCYANATE–HYDROGEN PEROXIDE SYSTEM.) hydrogen sulphide (H2 S) Certain bacteria can produce H2 S e.g. by the reductive degradation of sulphur-containing amino acids (e.g. cysteine) or by DISSIMILATORY SULPHATE REDUCTION; H2 S production can be plasmid mediated – see e.g. Hys plasmid in ESCHERICHIA. (See also KLIGLER’S IRON AGAR and TSI AGAR.) H2 S can be formed from sulphite by Saccharomyces cerevisiae [JGM (1985) 131 1417–1424]. H2 S can be used by some bacteria as an electron donor in lithotrophic metabolism; these bacteria include e.g. species of Beggiatoa and Thiobacillus, members of the Rhodospirillaceae and other photosynthetic bacteria, and the cyanobacterium Oscillatoria. (See also SULPHUR CYCLE.) hydrogen swell A SWELL caused by hydrogen production due to internal corrosion of the can (see also TIN). Hydrogen swells,

and then an oxygen atom is introduced into the ring (forming a lactone) by a cyclohexanone monooxygenase. The lactone can then be hydrolysed to form a (non-cyclic) dicarboxylic acid. Aromatic hydrocarbons (benzene, naphthalene, anthracene etc) are present in e.g. petroleum and are formed by the incomplete combustion of almost any organic material; they are therefore common pollutants, and many are recognized carcinogens. Bacteria (e.g. Pseudomonas spp) metabolize aromatic hydrocarbons by initially incorporating two atoms of oxygen into the substrate to form a cis-dihydrodiol; the reaction is catalysed by a multicomponent enzyme system comprising a dioxygenase, a flavoprotein, and IRON–SULPHUR PROTEINS. The cis-dihydrodiol is oxidized to a catechol which is in turn a substrate for another dioxygenase system which breaks open the aromatic ring. In contrast, fungi oxidize aromatic hydrocarbons using a cytochrome P-450-dependent monooxygenase to form a reactive arene oxide; this can either undergo isomerization to form a monohydric phenol, or enzymic hydrolysis to form a trans-dihydrodiol. [Reviews on microbial hydrocarbon metabolism: Book ref. 155.] Hydroclathrus See PHAEOPHYTA. Hydrodictyon A genus of freshwater green algae (division CHLOROPHYTA) which form free-floating net-like colonies (‘water nets’) composed of large, coenocytic cells. hydrogen (as a metabolite) Gaseous (molecular) hydrogen is produced e.g. in various types of FERMENTATION (sense 1), and is formed during NITROGENASE activity. Gaseous hydrogen may be consumed e.g. during METHANOGENESIS and may be used for lithotrophic metabolism by e.g. HYDROGEN-OXIDIZING BACTERIA and some SULPHATE-REDUCING BACTERIA. [Production and uptake of molecular hydrogen by unicellular cyanobacteria: JGM (1985) 131 1561–1569.] (See also FORMATE HYDROGEN LYASE and INTERSPECIES HYDROGEN TRANSFER.) hydrogen bacteria Syn. HYDROGEN-OXIDIZING BACTERIA. hydrogen dehydrogenase Syn. HYDROGENASE. hydrogen hypothesis See EUKARYOTE. hydrogen-oxidizing bacteria (the ‘hydrogen bacteria’; knallgas bacteria) A phrase sometimes used to refer specifically to a (non-taxonomic) category of aerobic bacteria which can grow chemolithoautotrophically by obtaining energy from the oxidation of gaseous hydrogen by oxygen via an electron transport chain (see KNALLGAS REACTION); most species can also grow chemoorganoheterotrophically and/or mixotrophically. [Details of the obligately chemolithoautotrophic hydrogenoxidizing species Hydrogenobacter thermophilus (gen. nov., sp. nov.): IJSB (1984) 34 5–10.] The hydrogen-oxidizing bacteria, sensu stricto, are distinct from those bacteria which can oxidize H2 without autotrophic CO2 fixation and/or which can carry out anaerobic oxidation of H2 coupled to the reduction of e.g. SO4 2− , CO2 or fumarate. The hydrogen-oxidizing bacteria (which include most or all CARBOXYDOBACTERIA) include e.g. those strains of Alcaligenes denitrificans formerly called A. ruhlandii ; Aquaspirillum autotrophicum; Bacillus schlegelii [JGM (1979) 115 333–341]; Paracoccus denitrificans; Pseudomonas facilis and P. saccharophila; and bacteria referred to as Alcaligenes eutrophus, Nocardia autotrophica, and N. opaca. Most hydrogen-oxidizing bacteria (including e.g. Paracoccus denitrificans) have only a membrane-bound, NAD-independent HYDROGENASE (see also EXTRACYTOPLASMIC OXIDATION); some strains have only a soluble (cytoplasmic), NAD-reducing hydrogenase (‘hydrogen dehydrogenase’), while others (e.g. strains of ‘Alcaligenes eutrophus’) have both forms of the enzyme. [Habitats, culture, and descriptions of individual hydrogenoxidizing bacteria: Book ref. 45, pp. 865–893.] 379

hydrogenase characterized by a high proportion of hydrogen in the headspace, may take months to develop; they are commonly associated with certain acidic fruits and with foods containing curing salts. hydrogenase An OXIDOREDUCTASE (EC 1.12.–. – ) which catalyses the reaction: H2 ↔ 2H+ + 2e− . Hydrogenases occur in various algae (see e.g. PHOTOREDUCTION) and e.g. in HYDROGENOXIDIZING BACTERIA, some SULPHATE-REDUCING BACTERIA, some nitrogen-fixing bacteria (see NITROGENASE), Chloroflexus aurantiacus [FEMS (1985) 28 231–235], and Escherichia coli (e.g. as part of the FORMATE HYDROGEN LYASE system). Hydrogenases are IRON–SULPHUR PROTEINS, and in many species of bacteria they have been shown to contain nickel. Hydrogen-oxidizing bacteria may contain a membrane-bound NAD-independent hydrogenase (see also EXTRACYTOPLASMIC OXIDATION) and/or a soluble NAD+ reducing hydrogenase (‘hydrogen dehydrogenase’). [Hydrogenases – their structure and applications in hydrogen production: Book ref. 132, pp. 75–102.] (See also KNALLGAS REACTION.) Hydrogenobacter See HYDROGEN-OXIDIZING BACTERIA. hydrogenogen See ACETOGEN. Hydrogenomonas An obsolete bacterial genus which included certain species of HYDROGEN-OXIDIZING BACTERIA (e.g. H. facilis, now Pseudomonas facilis). hydrogenosome A membrane-limited intracellular organelle present in certain eukaryotic microorganisms – e.g. trichomonads (but not e.g. Entamoeba histolytica); in trichomonads it contains various IRON–SULPHUR PROTEINS and flavoproteins as components of an electron transport chain that is used in the oxidation of pyruvate to acetate, CO2 and H2 (protons being used as electron acceptors). In isolated hydrogenosomes of Trichomonas vaginalis, METRONIDAZOLE is reduced, anaerobically, to an active (cytotoxic) derivative [JGM (1985) 131 2141–2144]; in vivo such active product(s) may damage the hydrogenosome itself and/or may leave the hydrogenosome and affect other target(s). (cf. MICROBODY.) hydrolases ENZYMES (EC class 3) which catalyse the hydrolytic cleavage of bonds, including C−O, C−N and C−C bonds. The names of such enzymes are commonly formed by adding ‘-ase’ to the name of the substrate (e.g. esterase, glycosidase, peptidase); the systematic name has the form substrate hydrolase. hydrophobia Syn. RABIES. hydrops fetalis (non-immune) A condition in which the fetus develops e.g. anaemia and oedema; death may result from severe anaemia. In a proportion of cases hydrops fetalis is due to infection by parvovirus B19 (see ERYTHROVIRUS). hydroresorufin See RESAZURIN TEST. hydrothermal vent In certain geographical locations: a region of the ocean floor where seawater, which has permeated the earth’s crust for several kilometres, emerges as a warm (5–25° C) or hot (270–380° C) hydrothermal fluid which is particularly rich in sulphide; vents which discharge hot fluids ≤300° C are called ‘white smokers’, while those discharging fluids at ca. 350° C are called ‘black smokers’ – an allusion to the clouds of black metal sulphides formed when these fluids meet the cold (2° C) ambient seawater. One of the best-studied vents is situated at the Gal´apagos Rift (near the equator at 86° W). The sulphide (and e.g. hydrogen, methane and ferrous iron) in hydrothermal fluids supports the chemolithotrophic growth of various bacteria (e.g. species of THIOBACILLUS and THIOMICROSPIRA) – thus permitting chemosynthetic PRIMARY PRODUCTION; these bacteria form the basis of a food chain which supports communities of e.g. giant clams, limpets, mussels and tube worms in and around the vents. Some of the lithotrophic prokaryotes form symbiotic associations with some of the invertebrates;

thus, e.g. prokaryotes occur in the gill cells of the giant clam (Calyptogena magnifica) and in the TROPHOSOME tissue of the giant tube worm, Riftia pachyptila. A living community at a given vent appears to last for several years to several decades. [Biology and microbiology of hydrothermal vents: Science (1985) 229 713–725; evidence for chemosynthetic primary production in hydrothermal vents: Book ref. 202, pp. 319–360.] hydroxamates (in iron uptake) See SIDEROPHORES. hydroxyapatite (hydroxylapatite; Ca10 (PO4 )6 (OH)2 ) A mineral which is used as a stationary phase in adsorption CHROMATOGRAPHY e.g. for separating ssDNA from dsDNA or RNA. Under certain ionic conditions the mineral adsorbs dsDNA; the dsDNA is desorbed at higher ionic concentrations. hydroxycobalamin See VITAMIN B12 . hydroxyethylcellulose See HE-CELLULOSE. hydroxyl radical (OH· or ·OH) A hyper-reactive radical formed e.g. during a reaction involving SUPEROXIDE and HYDROGEN PEROXIDE (the ‘Haber–Weiss reaction’); this reaction can be catalysed by iron complexes (e.g. Fe–EDTA, Fe–transferrin) and may be represented in two phases: (i) the reduction of ferric (with the formation of ferrous complexes and complexes by O− 2˙ SINGLET OXYGEN), and (ii) the oxidation of ferrous complexes by H2 O2 (with the formation of ferric complexes, OH− and OH·) [FEBS (1978) 86 139–142]. (Hydroxyl radical is also reported to be formed e.g. in a reaction involving superoxide and hypochlorite, and by the action of ultraviolet radiation on hydrogen peroxide.) During PHAGOCYTOSIS, LACTOFERRIN from activated NEUTROPHILS may catalyse the formation of OH·, thus enhancing antimicrobial activity. Scavengers of OH· used in experimental systems include e.g. benzoate, dimethyl sulphoxide, mannitol and salicylate. hydroxylamine (as a MUTAGEN) Hydroxylamine (NH2 OH) reacts mainly with cytosine residues (and, much more slowly, with adenine residues) in DNA (particularly ssDNA), replacing the amino group with a hydroxyamino group (−NHOH); this favours tautomerization of the base such that, during subsequent DNA replication, mispairing occurs (resulting predominantly in G·C to A·T transitions). Although hydroxylamine is an effective mutagen when used to treat certain viruses or e.g. transforming DNA, any mutagenic effect it may have in living cells is generally masked by its toxic or lethal effects. The related compound methoxyamine (NH2 OCH3 ) acts in a similar way. hydroxylapatite Syn. HYDROXYAPATITE. hydroxylase Syn. MONOOXYGENASE. hydroxymethionine analogue See HMA. 6-(p-hydroxyphenylazo)uracil See HPURA. hydroxypyrimidine antifungal agents A group of agricultural systemic ANTIFUNGAL AGENTS which have a highly selective action against powdery mildews; resistance to these fungicides tends to develop rapidly. Hydroxypyrimidines include e.g. DIMETHIRIMOL and ETHIRIMOL. 8-hydroxyquinoline (oxine; 8-quinolinol) (as antimicrobial agent) A chelating agent which, in the presence of Cu2+ or Fe2+ , has antifungal and antibacterial activity; Gram-positive bacteria are much more susceptible than Gram-negative bacteria. The potentiating effects of Cu2+ and Fe2+ are antagonized by trace amounts of Co2+ , while Ni2+ acts as a competitive inhibitor. COPPER –oxine has been used in agricultural antifungal sprays and as a rot-proofing agent for e.g. textiles. Some halogenated derivatives of oxine are used e.g. for the treatment or prophylaxis of amoebic dysentery. They include 380

hypha hypericin See STENTORIN. hyper-IgM syndrome See RNA EDITING. hyperimmune Refers to the condition of an individual whose plasma contains a high titre of a particular antibody following repeated exposure of the individual to the homologous antigen. Hyperimmune serum is serum derived from such an individual. Hypermastigida An order of protozoa (class ZOOMASTIGOPHOREA) which have numerous flagella, the kinetosomes being arranged in complete or incomplete circles; the organisms are associated with insects. Genera: e.g. Barbulanympha, Lophomonas, Microjoenia, Spirotrichonympha, TRICHONYMPHA. hyperparasite A parasite of a parasite. hyperplasia The enlargement of an organ or tissue owing to an increase in the number of cells. (Hence adj. hyperplastic.) (cf. HYPERTROPHY and NEOPLASIA.) hypersensitivity (1) (immunol.) The state of a PRIMED individual who, on further exposure to the relevant antigen, gives an exaggerated immune response that causes varying degrees of harm – ranging from a mild local inflammatory reaction to death. (See IMMEDIATE HYPERSENSITIVITY and DELAYED HYPERSENSITIVITY; see also BRUCELLOSIS.) (2) (plant pathol.) The expression of extreme reactivity by a plant in response to a potential parasite or pathogen, the plant’s response commonly serving to limit or prevent parasitization/disease. Hypersensitivity typically involves rapid cell death at the (localized) site of infection and the concomitant induction of e.g. PHYTOALEXIN(s) by microbial elicitors; the induction of phytoalexins by microbial elicitors involves the expression of new host genes and the formation of new species of mRNA and new enzymes. (In addition to phytoalexin production, microbial elicitors can also apparently e.g. stimulate the formation of ETHYLENE and bring about the accumulation of LIGNIN.) (See also PATHOGENESIS-RELATED PROTEINS.) In many cases the combination of cell death and accumulation of phytoalexin(s) at the site of infection appears to provide the level of resistance needed to prevent disease development. When the challenging microorganism is an obligate parasite (i.e., a BIOTROPH), the death of host cells may, in itself, be sufficient to prevent the spread of the parasite to uninfected tissues. hypersensitivity pneumonitis Syn. EXTRINSIC ALLERGIC ALVEOLITIS. hypertrophy Enlargement of an organ or tissue owing to an increase in the size of pre-existing cells. (cf. HYPERPLASIA.) hypervariable region (immunol.) Any of several amino acid sequences, located in the VARIABLE REGIONS of the heavy chain and light chain of IMMUNOGLOBULINS, which exhibits a degree of variability (in composition) greater than that found in other parts of the variable region. (See also COMPLEMENTARITY-DETERMINING REGIONS.) hypha (pl. hyphae) (1) (bacteriol., mycol.) In many (mycelial) fungi and in some bacteria (see ACTINOMYCETALES): a branched or unbranched filament, many of which together constitute the vegetative form of the organism and (in some species) form the sterile portion of a fruiting body; a mass of vegetative hyphae is referred to as a MYCELIUM. Fungal hyphae. Each hypha has a tubular CELL WALL which, in many species, is divided into compartments or cells by crosswalls (see SEPTUM (b)); in both septate and aseptate species, the cell wall is external to the CYTOPLASMIC MEMBRANE which encloses the cytoplasm, NUCLEUS or nuclei, and other components typical of eukaryotic organization. (See also VACUOLE.) The diameter of a hypha ranges from about 1 µm to macroscopic dimensions, depending e.g. on species. Hyphae grow mainly by apical extension – see GROWTH (fungal).

7-iodo-8-hydroxyquinoline-5-sulphonate (chiniofon); 5,7-diiodo8-hydroxyquinoline (diiodohydroxyquin; Diodoquin); 5-chloro7-iodo-8-hydroxyquinoline (iodochlorohydroxyquin; Enterovioform; Vioform). (Some of these derivatives also have useful antibacterial and antifungal properties.) hydroxyquinoline-N-oxide (HOQNO; HQNO) 2-Alkyl-4-hydroxyquinoline-N-oxides (e.g. 2-n-heptyl-4-HOQNO) act as RESPIRATORY INHIBITORS in mitochondria and in certain bacteria – some bacteria are apparently impermeable to HOQNOs; HOQNOs appear to resemble ANTIMYCIN A (q.v.) in their mode of action. HOQNOs also inhibit the Na+ pump in Vibrio alginolyticus (see SODIUM MOTIVE FORCE). 2-hydroxystilbamidine An aromatic DIAMIDINE which has trypanocidal and antifungal activity; it has been used e.g. in the treatment of blastomycosis and African trypanosomiasis. 5-hydroxytryptamine Syn. SEROTONIN. hydroxyurea (HU; HONH.CO.NH2 ) A reagent which prevents the synthesis of deoxyriboNUCLEOTIDES by specifically inhibiting ribonucleoside diphosphate reductase. Hyella See PLEUROCAPSA GROUP. Hygrocybe See AGARICALES (Hygrophoraceae). hygromycin B An AMINOGLYCOSIDE ANTIBIOTIC which, like STREPTOMYCIN, appears to act at a single ribosomal site. hygrophilic (hygrophilous) Requiring a moist habitat for optimum growth. Hygrophoraceae See AGARICALES. Hygrophorus See AGARICALES (Hygrophoraceae). hymenium (mycol.) A layer of ascospore- or basidiosporeforming tissue – e.g. that lining an APOTHECIUM or that forming the surface of a LAMELLA; a hymenium may also contain sterile structures – see e.g. PARAPHYSIS and PSEUDOPARAPHYSIS. Hymenochaetaceae See APHYLLOPHORALES. Hymenochaete See APHYLLOPHORALES (Hymenochaetaceae). Hymenogaster See GASTEROMYCETES (Hymenogastrales). Hymenogastrales See GASTEROMYCETES. Hymenomonas See COCCOLITHOPHORIDS. Hymenomycetes A class of fungi (subdivision BASIDIOMYCOTINA) in which the typical fruiting body is a well-developed, macroscopic, gymnocarpous or semiangiocarpous structure containing BALLISTOSPORE-bearing basidia in a HYMENIUM. Subclasses: HOLOBASIDIOMYCETIDAE and PHRAGMOBASIDIOMYCETIDAE. hymenophore That part of a fruiting body which bears a HYMENIUM or SUBHYMENIUM, or the entire (hymenium-bearing) fruiting body. (cf. SPOROPHORE.) Hymenostomatia A subclass of (mostly) freshwater ciliates (class OLIGOHYMENOPHOREA) in which somatic ciliature is often uniform, the buccal cavity (when present) is ventral, and kinetodesmata are usually conspicuous; sedentary and colonial types are not common. Orders: ASTOMATIDA, HYMENOSTOMATIDA, SCUTICOCILIATIDA. Hymenostomatida An order of protozoa (subclass HYMENOSTOMATIA) in which the buccal cavity is well defined and contains characteristic membranelles. A SCUTICA does not appear during stomatogenesis. Genera (which may be distinguished e.g. by the number of post-oral kineties) include e.g. COLPIDIUM, Frontonia, GLAUCOMA, ICHTHYOPHTHIRIUS, LAMBORNELLA, Ophryoglena, PARAMECIUM and TETRAHYMENA. hyperauxinic Containing or producing abnormally high levels of AUXINS. hyperchromic shift A change in the amount of ultraviolet radiation absorbed by a nucleic acid during changes from the double-stranded to the single-stranded condition, or vice versa (see e.g. THERMAL MELTING PROFILE). 381

hyphal body In basidiomycetes the primary hyphae are uninucleate haploid hyphae which develop when basidiospores germinate; the secondary (dikaryotic) hyphae develop following DIKARYOTIZATION. A basidiocarp may, according to species, consist of one, two or three distinct types of hypha – corresponding, respectively, to a monomitic, dimitic or trimitic sporocarp. A monomitic sporocarp contains only generative hyphae: typically thin-walled, branched, septate hyphae which give rise to basidia; generative hyphae may contain CLAMP CONNECTIONS if the organism normally forms clamps on its vegetative mycelium. A dimitic sporocarp contains generative hyphae together with either skeletal hyphae or binding hyphae (both of which originate from generative hyphae). Skeletal hyphae are typically thick-walled and unbranched; they are sterile (i.e., do not form basidia) and do not form clamps. Binding (= ligative) hyphae are sterile, highly branched, and do not form clamps; in trimitic sporocarps they bind together the generative and skeletal hyphae. (2) (bacteriol.) See PROSTHECA. hyphal body In some species of the ENTOMOPHTHORALES: a piece of fragmented mycelium which can germinate to form a sporebearing structure. hyphenated dyad symmetry See e.g. PALINDROMIC SEQUENCE. Hyphochytriaceae See HYPHOCHYTRIOMYCETES. Hyphochytriales See HYPHOCHYTRIOMYCETES. Hyphochytridiomycetes See HYPHOCHYTRIOMYCETES. Hyphochytriomycetes A class of fungi (subdivision MASTIGOMYCOTINA) which form zoospores having one anteriorly-directed tinsel flagellum. The organisms include terrestrial species as well as aquatic saprotrophs and parasites of other fungi and of freshwater and marine algae; they closely resemble members of the CHYTRIDIALES in morphology and life cycle, but they apparently do not carry out sexual processes. One order: Hyphochytriales; three families: Anisolpidiaceae, Hyphochytriaceae and Rhizidiomycetaceae (e.g. RHIZIDIOMYCES). This class has been called ‘Hyphochytridiomycetes’ by many authors. [Validation of the name ‘Hyphochytriomycetes’: Book ref. 174, p. 285.] Hypholoma See AGARICALES (Strophariaceae). Hyphomicrobium A genus of PROSTHECATE BACTERIA found in soils and in freshwater, estuarine and marine habitats. Morphologically, Hyphomicrobium resembles RHODOMICROBIUM, and its cell cycle is very similar to the ‘simplified’ cell cycle of R. vannielii ; it differs from R. vannielii e.g. in the absence of pigments and in that its swarm cells bear a single subpolar flagellum. (Phages specific for developing daughter cells have been isolated [JGV (1979) 43 29–38].) The organisms are chemoorganotrophs which can use one-carbon compounds (e.g. methanol, methylamine) as sole sources of carbon and energy (see METHYLOTROPHY); one-carbon compounds are metabolized via the icl− serine pathway. Growth occurs either aerobically or anaerobically with nitrate (which is reduced to nitrogen via nitrite); optimum growth temperature: 25–30° C. GC%: ca. 59–67. [Review: ARM (1981) 35 567–594.] Hyphomonas A genus of Gram-negative, aerobic, asporogenous, non-photosynthetic, heterotrophic, PROSTHECATE BACTERIA which reproduce by budding; daughter cells are motile (swarm cells), having one or more flagella according to species. The cell body may vary in size and shape during the cell cycle, and usually has a single polar prostheca (‘hypha’). Iron and manganese salts are not deposited on the cell surface (cf. PEDOMICROBIUM). Amino acids are the preferred substrates for growth; onecarbon compounds are not used (cf. HYPHOMICROBIUM). Species:

H. neptunium (isolated from seawater) and H. polymorpha (type species, isolated from nasal mucus from a patient with sinusitis) [IJSB (1984) 34 71–73]. Proposed species: H. hirschiana, H. jannaschiana and H. oceanitis [IJSB (1985) 35 237–243]. Hyphomycetales See HYPHOMYCETES. Hyphomycetes A class of fungi of the subdivision DEUTEROMYCOTINA; most of the conidium-forming species do not form conidiomata (order Hyphomycetales), while the others form sporodochia (order Tuberculariales) or synnemata (order Stilbellales) – and some species do not form conidia at all (order AGONOMYCETALES). (cf. COELOMYCETES.) The vegetative form of the organisms is commonly a well-developed mycelium, but the class includes some fungi which can grow as unicellular organisms and which are sometimes classified in the class BLASTOMYCETES. The class Hyphomycetes (ca. 1000 genera) includes e.g. ACICULOCONIDIUM, ACREMONIUM, ALTERNARIA, ARTHROBOTRYS, ASPERGILLUS, AUREOBASIDIUM, BEAUVERIA, BLASTOMYCES, BOTRYTIS, BRETTANOMYCES, CALCARISPORIUM, CANDIDA, CERCOSPORA, Chalara, CHRYSOSPORIUM, Cladobotryum, CLADOSPORIUM, COCCIDIOIDES, CRYPTOCOCCUS, CRYPTOSTROMA, CULICINOMYCES, Curvularia, CYLINDROCARPON, DACTYLARIA, DACTYLELLA, DRECHSLERA, Exophiala, Fonsecaea, FULVIA, FUSARIUM, GEOTRICHUM, Gliocladium, Gonatobotrys, Gonatobotryum, GRAPHIUM, HARPOSPORIUM, HELMINTHOSPORIUM, HIRSUTELLA, HISTOPLASMA, HORMOCONIS, HUMICOLA, HYPHOZYMA, KLOECKERA, MADURELLA, MALASSEZIA, MERIA, METARHIZIUM, MONACROSPORIUM, Monodictys, Mycocentrospora, MYCOGONE, MYROTHECIUM, NOMURAEA, Oidiopsis, Oidium, OOSPORIDIUM, Ovulariopsis, PAECILOMYCES, PARACOCCIDIOIDES, PENICILLIUM, Periconia, Pesotum, PHAFFIA, PHIALOPHORA, PITHOMYCES, PSEUDOCERCOSPORELLA, PYRICULARIA, Ramularia, RHINOCLADIELLA, RHODOTORULA, RHYNCHOSPORIUM, Scedosporium, SCHIZOBLASTOSPORION, Scopulariopsis, Sphacelia, SPOROTHRIX, SPOROTRICHUM, STACHYBOTRYS, STENELLA, STERIGMATOMYCES, THERMOMYCES, THIELAVIOPSIS, Tolypocladium, TORULA, TRICHODERMA, TRICHOSPORON, TRICHOTHECIUM, TRIGONOPSIS, Triposporina, Tritirachium, VERTICILLIUM, WANGIELLA, XYLOHYPHA, ZALERION. hyphomycosis destruens Syn. EQUINE PHYCOMYCOSIS. hyphopodium In the mycelium of the BLACK MILDEWS: a short, one- or two-celled branch on a somatic hypha. In a capitate hyphopodium the distal cell is enlarged; this type of hyphopodium may act as an appressorium and give rise to a haustorium. Hyphozyma A genus of yeast-like fungi of the HYPHOMYCETES. [Key to species: AvL (1986) 52 39–44.] hypnospore A thick-walled resting cell. hypnozoite A dormant form of a parasite in a living host. (See e.g. PLASMODIUM.) hypobiosis See DORMANCY. Hypocenomyce See LECIDEA. hypochlorites (as antimicrobial agents) Hypochlorites (and hypochlorous acid) are strong OXIDIZING AGENTS which are microbicidal e.g. for many bacteria (including endospores) and viruses; their antimicrobial activity is not inhibited by most anionic and non-ionic detergents, but they are readily inactivated by organic matter and they have a tendency to decompose, forming e.g. chlorate (ClO3 − ) and HCl. (Decomposition is enhanced by e.g. heavy metal ions, acidity, light, and heat.) In solution, hypochlorites occur in equilibrium with hypochlorous acid, HOCl. The highly microbicidal undissociated form of HOCl is favoured by low pH; however, low pH reduces the stability of hypochlorites, so that commercial 382

Hyuga fever sodium hypochlorite solutions are often stabilized with sodium hydroxide. Sodium hypochlorite is used in a range of DISINFECTANTS and bleaches (e.g. Chloros, Domestos, Milton). Aerosols of hypochlorite solutions have been used for the disinfection of air. (N.B. Hypochlorite solutions react with formaldehyde to form the carcinogen bis-chloromethylether.) (See also DICHLOROISOCYANURATE.) hypocone See DINOFLAGELLATES. Hypocrea See HYPOCREALES. Hypocreales An order of mainly saprotrophic, plant-parasitic or fungicolous fungi of the subdivision ASCOMYCOTINA; anamorphs occur e.g. in the genera ACREMONIUM, CYLINDROCARPON and FUSARIUM. Ascocarp: perithecioid or closed, frequently on or within a stroma and often brightly coloured. Asci: cylindrical to clavate. Ascospores: usually colourless, aseptate to multiseptate or muriform. Some genera in the order have traditionally been distinguished on the basis of the number of septa in their ascospores; spore septation has not been recognized as a valid taxonomic criterion [Mycol. Pap. (1983) Nr 150 ]. Genera: e.g. Calonectria, GIBBERELLA, Hypocrea, NECTRIA. Hypocrella See CLAVICIPITALES. Hypoderma See RHYTISMATALES. hypogean Occuring underground (cf. EPIGEAN). Hypogymnia A genus of LICHENS (order LECANORALES). The thallus is foliose, with often hollow, inflated lobes, grey to greyishbrown above, black beneath; rhizines are absent. H. physodes is very common e.g. in the UK; it is tolerant of air pollution and is often the only macrolichen to be found in and around towns and cities. hypolimnion In a lake: the layer of water between the METALIMNION and the lake bottom; characteristically, it is anaerobic and rich in sulphide. Hypomyces A genus of mainly fungicolous fungi of the order CLAVICIPITALES; anamorph: Cladobotryum. (See also COBWEB DISEASE.) hyponeuston See NEUSTON. hypophloeodal Syn. ENDOPHLOEODAL. Hypopylaria A category (‘section’) of LEISHMANIA species which develop in the midgut and hindgut of the arthropod vector; it includes ‘L. agamae’ and ‘L. ceramodactyli ’. (cf. PERIPYLARIA, SUPRAPYLARIA.) hyposensitization (immunol.) Syn. DESENSITIZATION. Hyposoter exiguae virus See POLYDNAVIRIDAE. hypostatic allele See EPISTASIS. Hypostomatia A subclass of ciliates (class KINETOFRAGMINOPHOREA) in which the cytostome (when present) generally occurs on the ventral surface, and the cytopharyngeal apparatus is of the CYRTOS type; the body is typically cylindrical or dorsoventrally flattened, and the somatic ciliature is often reduced. The orders are: Apostomatida. Cytostome inconspicuous or absent; rosette (secretory organelle?) commonly present in the oral area; somatic ciliature spirally arranged in mature organisms; cysts common (see also TOMITE); often associated with marine

crustacea. Genera: e.g. Chromidina, Foettingeria, Gymnodinioides, Polyspira. Chonotrichida. Typically vase-shaped and sedentary with a non-contractile stalk, attached to crustacea; reproduction by budding, producing motile ciliated forms (see also BROOD POUCH); ciliature in adult cell restricted to atrial region. Genera: e.g. Actinichona, CHILODOCHONA, Spirochona, Stylochona. Cyrtophorida. Body flattened, FRANGE absent or vestigial. Genera: e.g. CHILODONELLA, Chlamydodon, Dysteria, Hartmannula. Nassulida. Frange typically limited and restricted to left side of ventral surface. Genera: e.g. Microthorax, NASSULA, Pseudomicrothorax. Rhynchodida. Cells with a single, TOXICYST-bearing anterior tentacle, typically associated with the gills of marine bivalve molluscs. Genera: e.g. Ancistrocoma. Synhymeniida. Body commonly cylindrical and completely ciliated; frange extensive. Genera: e.g. Orthodonella. hypothallus (1) (prothallus) (lichenol.) A pale or black layer of non-lichenized (i.e. photobiont-free) hyphae which extends from the periphery of the thallus in certain crustose (or squamulose) lichens; a hypothallus may also be evident between the areolae of certain areolate species (see e.g. RHIZOCARPON). (2) (of myxomycetes) A thin, often transparent, sometimes calcified deposit which is secreted by the plasmodium during fruiting, and which forms a base for the fruiting bodies, remaining on the substratum following fruiting body formation. In some cases the hypothallus may be simply a remnant of the plasmodial slime sheath. hypotheca (1) See DINOFLAGELLATES. (2) See DIATOMS. hypothecium See APOTHECIUM. Hypotrichida An order of typically free-living ciliate protozoa (class POLYHYMENOPHOREA). Cells: typically ovoid to elongate and dorsoventrally flattened, with a conspicuous oral ciliature and a number of groups of cirri on the ventral side; the dorsal side often carries pairs of short cilia (‘sensory bristles’). Genera include e.g. ASPIDISCA, EUPLOTES, Histriculus, Holosticha, Isosticha, Klonostricha, Oxytricha, Psammomitra, Strongylidium, Stylonychia, Trachelostyla, Uronychia, Urosoma, Urostyla. hypovalve See DIATOMS. hypovirulence A reduced level of virulence in a strain of pathogen due e.g. to genetic changes in the pathogen, or to the effects on the pathogen of an infectious agent (contagious or transmissible hypovirulence: see e.g. CHESTNUT BLIGHT and DUTCH ELM DISEASE). hypoxanthine The base in the nucleoside inosine [see Appendix V(a) for structure]. (See also NITROUS ACID and WOBBLE HYPOTHESIS.) hypoxanthine-DNA glycosylase See NITROUS ACID. Hypoxylon See SPHAERIALES. Hys plasmid See ESCHERICHIA. hystrichosphaerids (hystrichospheres; hystricospores) Fossil resting spores of DINOFLAGELLATES; they date from the late Triassic onwards. [Book ref. 136, pp. 847–964.] Hyuga fever See EHRLICHIA.

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Dictionary of Microbiology and Molecular Biology, Third Edition Paul Singleton and Diana Sainsbury © 2006 John Wiley & Sons Ltd. ISBN: 0-470-03545-5

I I Isoleucine (see AMINO ACIDS). (I + C + D) model Syn. HELMSTETTER–COOPER MODEL. I-like pili See PILI. I period See HELMSTETTER–COOPER MODEL. Ia antigens Class II antigens of the murine MAJOR HISTOCOMPATIBILITY COMPLEX. (See also IR GENES.) Ia protein The Escherichia coli OmpF PORIN. IAA Indole 3-acetic acid (see AUXINS). IAEA International Atomic Energy Agency. IAHS Infection-associated haemophagocytic syndrome: see HAEMOPHAGOCYTIC SYNDROME. IAM Institute of Applied Microbiology, University of Tokyo, Yayoi, Bunko-Ku, Tokyo, Japan. IAP Intracisternal A-TYPE PARTICLE. iatrogenic Refers to any disease or infection which is caused or exacerbated, unintentionally, as a result of medical intervention – e.g. examination or treatment. IAVI International AIDS Vaccine Initiative. Ib protein The Escherichia coli OmpC PORIN. ibotenic acid See AMATOXINS. IBV Infectious bronchitis virus (CORONAVIRIDAE). ICAD See APOPTOSIS. ICAM-1 Syn. CD54. ICAM-2 See CD102. ICAM-3 See IMMUNOGLOBULIN SUPERFAMILY. ICDH Isocitrate dehydrogenase: see TCA CYCLE. ICE (syn. caspase-1) See APOPTOSIS. ice algae See DIATOMS. ice nucleation bacteria Those bacteria which, at temperatures just below 0° C, promote water-to-ice transition by acting as nuclei around which ice crystals can form. Such bacteria (e.g. strains of Erwinia herbicola, Pseudomonas fluorescens, P. syringae and Xanthomonas campestris) – which include some common epiphytes – have been implicated as contributory factors in frost damage in various agricultural crops. A DNA fragment from P. fluorescens, when cloned in Escherichia coli, can confer the ice-nucleation phenotype; the fragment may encode an OUTER MEMBRANE protein of MWt ca. 180000 [EMBO (1986) 5 231–236]. When grown at 15° C, most ice-nucleation-positive strains of Erwinia herbicola shed into the medium vesicles composed of outer membrane; these vesicles (‘cell-free ice nuclei’) can behave as ice-nucleation centres which are active at −2° C to −10° C [JB (1986) 167 496–502]. Some plant tissues survive, without damage, when ‘supercooled’ to several degrees below 0° C – but may suffer frost damage if ice-nucleation bacteria are present. Above (approx.) −5° C, the incidence of frost injury can be decreased by reducing the size of the populations of plant-contaminating ice-nucleation bacteria. This can be done e.g. by treatment of plant surfaces with antibiotics such as streptomycin or oxytetracycline; an alternative method is to treat plant surfaces with non-ice-nucleating bacteria (a form of BIOLOGICAL CONTROL). A combination of antibiotic treatment and biological control has been found to act additively in the control of frost injury in pear trees [Phytopathol. (1996) 86 841–848]. Iceland moss See CETRARIA. ich See ICHTHYOPHTHIRIASIS. ichthyo- Prefix denoting fish – e.g. ichthyopathology: the study of FISH DISEASES; ichthyotoxic: toxic to fish.

ichthyophonosis A systemic, granulomatous FISH DISEASE caused by Ichthyophonus hoferi (see ICHTHYOPHONUS); external symptoms vary in nature and severity (cf. TAUMELKRANKHEIT). I. hoferi occurs in various host tissues, mainly as spherical, thick-walled, multinucleate cells (‘cysts’, ‘resting spores’) up to 200 µm or more in diameter; immediately after the death of the host the ‘cysts’ germinate to form branching hyphae. The disease can affect e.g. mackerel and salmonids, and has caused mass fatalities in Atlantic herring; infected fish are, or rapidly become, unsuitable for human consumption as the muscles rapidly degenerate after the death of the fish. [Review: Book ref. 1, pp. 243–269.] Ichthyophonus A genus of fungi (or protozoa? – taxonomic affinity unknown) parasitic in fish. Species: I. hoferi (see ICHTHYOPHONOSIS) and I. gasterophilum. (cf. ICHTHYOSPORIDIUM.) ichthyophthiriasis (white spot, ich, ick) A freshwater FISH DISEASE caused by the ciliate Ichthyophthirius multifiliis. White spots 1 mm or so across, each containing one or more ciliates, appear on skin and fins; affected fish are weakened and may die. Secondary SAPROLEGNIASIS is common. I. multifiliis needs well-oxygenated waters and may be controlled e.g. by raising the temperature to diminish dissolved oxygen levels. Ichthyophthirius A genus of ciliates (order HYMENOSTOMATIDA); I. multifiliis is the causal agent of ICHTHYOPHTHIRIASIS in freshwater teleost fish. (cf. CRYPTOCARYON.) The life cycle of I. multifiliis involves three stages. The stage infective for fish is an ovoid or fusiform cell (called a tomite or theront), ca. 15 × 40 µm, which is covered with cilia, and which has a filamentous projection at the anterior end. Within the fish’s epidermis the tomite becomes spherical and develops an oral apparatus – becoming a trophozoite (= trophont) which grows to ca. 100–1000 µm diam. When free of the host, the trophozoite forms a gelatinous exocyst, loses its oral apparatus, and undergoes schizogony. Cysts, each several hundred micrometres in size, may contain up to ca. 1000 tomites which are released to complete the life cycle. [SEM of stages in the life cycle of I. multifiliis: J. Parasitol. (1985) 71 218–226; development of I. multifiliis in gill epithelium: JP (1986) 33 369–374.] Ichthyosporidium A genus used by some to include members of the genus ICHTHYOPHONUS, and by others to include microsporidean protozoa parasitic in fish. ichthyotoxin A TOXIN which is active against fish. ick See ICHTHYOPHTHIRIASIS. icl See SERINE PATHWAY. ICL Isocitrate lyase: see TCA CYCLE and SERINE PATHWAY. icm genes (of Legionella pneumophila) See end of section (a) in PHAGOCYTOSIS. ICMSF International Commission on Microbiological Specifications for Foods, an organization of the International Union of Microbiological Societies. ICNV International Committee on Nomenclature of Viruses, superseded by the ICTV. icosahedral symmetry (5-3-2 symmetry) The symmetry exhibited by an ICOSAHEDRON and by the capsid of certain types of virus: 5-fold rotational symmetry through each of the 12 apexes; 3-fold rotational symmetry about an axis through the centre of each of the 20 triangular faces; and 2-fold rotational symmetry about an axis through the centre of each of the 30 edges. 384

IgA1 proteases IDAV See HIV. idiogram See KARYOTYPE. idiolite A product of SECONDARY METABOLISM. idiopathic (of a disease) Of unknown cause. idiophase In BATCH CULTURE, that phase in which SECONDARY METABOLISM is dominant (cf. TROPHOPHASE); it corresponds to the latter part of the log phase together with the stationary phase. idiosome (protozool.) See XENOSOME (2). idiotope See IDIOTYPE. idiotype An Ig molecule defined by the sum total of antigenic determinants (idiotopes) on its variable (VH and/or VL ) domains. idli A type of steamed bread from India. It is made from a batter of milled rice and black gram (Phaseolus mungo) which is left to ferment overnight. The fermentation is carried out mainly by Leuconostoc mesenteroides which produces acid and gas; Enterococcus faecalis, and sometimes Pediococcus cerevisiae, contribute acidity, and yeasts may also be involved. The leavened batter is then steamed. idling During DNA replication: repeated cycles of addition and excision of nuleotides at a 3′ terminal with no net synthesis or degradation of DNA. [Idling as a mechanism in lagging strand synthesis: GD (2004) 18 2764–2773.] idoxuridine (IDU; 5-iodo-2′ -deoxyuridine; IUdR) An ANTIVIRAL AGENT which acts as an analogue of thymidine (5-methyl-2′ deoxyuridine). Selective toxicity is poor, and the drug is too toxic for systemic use; it may be used topically for the treatment of e.g. herpes simplex keratitis, but is being superseded by more recent antiviral drugs. IDU IDOXURIDINE. IEF ISOELECTRIC FOCUSING. IEM IMMUNOELECTRON MICROSCOPY. IEP (1) ISOELECTRIC POINT. (2) IMMUNOELECTROPHORESIS. IF INTERMEDIATE FILAMENT. IF-1, IF-2, IF-3 See PROTEIN SYNTHESIS. IF1 protein See PROTON ATPASE. IFA test Syn. IFAT. IFAT See indirect IMMUNOFLUORESCENCE. IFN INTERFERON. IFO Institute for Fermentation, 17–85 Juso-Honmachi, 2-Chome, Yodogawa-Ku, Osaka, Japan. IFT Syn. IFAT. Ig IMMUNOGLOBULIN. IgA Immunoglobulin A, the predominant IMMUNOGLOBULIN in saliva, tears, colostrum and other body fluids, but comprising only ca. 10% of the total plasma Igs. The IgA monomer (MWt ca. 160000; S20 W 7) contains alpha HEAVY CHAINS, kappa or lambda LIGHT CHAINS, and ca. 8% carbohydrate. Most IgA at mucosal surfaces (secretory IgA, sIgA, SIgA) is in dimeric form: two monomers are linked via a J CHAIN, and the whole is linked to the SECRETORY COMPONENT. Polymers larger than dimers are also formed. IgA can fix complement via the alternative pathway. There are two subclasses: IgA1 and IgA2. (See also entry IgA1 proteases.) IgA1 proteases Various extracellular bacterial enzymes which specifically cleave the human IgA1 antibody at the heavychain hinge region – but which do not affect IgA2; some are sensitive to EDTA. These enzymes are synthesized by e.g. Haemophilus influenzae, Neisseria gonorrhoeae, N. meningitidis and Streptococcus pneumoniae – bacteria which are typically pathogenic at or via the mucosal surfaces; presumably, IgA1 proteases counteract the host’s IgA1 defences, but the role of these enzymes in pathogenesis has not been established. At least some IgA1 proteases are secreted by a type IV system (see PROTEIN SECRETION).

A viral capsid having strict icosahedral symmetry would be constructed from exactly 60 identical building units arranged in positions of exact equivalence on the surface of a hypothetical sphere, the units being held together via identical (strictly equivalent) interunit contacts throughout. In most viruses, however, the genome is too large to fit into a capsid composed of 60 reasonably sized units, and in many ‘icosahedral’ viruses the number of units which form the capsid is a certain multiple of 60 (n60); in some viruses (e.g. polioviruses) the n60 units include units of more than one type, while in other viruses all the units are identical. The construction of a symmetrical capsid with n60 units requires that the units be arranged in 60-unit sets, the members of each set being distributed throughout the capsid. In such an arrangement of (n60) units, the interunit contacts are not precisely identical throughout the capsid; however, since all interunit bonding involves the same general type of contact, the interunit bonds in such a capsid are described as ‘quasi-equivalent’. In the smaller icosahedral capsids consisting of n60 units, the units are (of necessity) arranged into 5- and 6-membered rings, each ring forming a tight cluster – referred to as a PENTAMER or hexamer, respectively – that may be distinguishable in electron micrographs; the clustering of units in this way maximizes contact between the units. In such capsids a pentamer occupies each of the 12 apexes. (The existence of 5- or 6-membered clusters does not necessarily mean that members of a given cluster are bound more strongly to each other than they are to adjacent units; thus, e.g. many viruses which have 180-unit capsids yield dimers (2-unit particles) when gently disrupted.) In some cases a pentamer or hexamer may appear, under the electron microscope, as a single entity – which may be referred to as a morphological unit or capsomer (= capsomere). In those icosahedral viruses whose capsids comprise up to 240 building units, the value of n (in n60) can be 1, 3 or 4 (depending on virus); in these viruses, n (i.e., the number of 60-unit sets in the capsid) corresponds to the triangulation number (T number, or T). The large icosahedral viruses (e.g. adenoviruses) deviate from the geometrical and structural criteria obeyed by the smaller icosahedral viruses. [Principles of virus structure: Book ref. 148, pp. 27–44.] icosahedron A solid figure contained by 20 plane faces, all the faces being equilateral triangles of the same size. Many viruses have ICOSAHEDRAL SYMMETRY. ICP (insecticidal crystal protein) See BIOLOGICAL CONTROL. ICPB International Collection of Phytopathogenic Bacteria, Department of Bacteriology, University of California, Davis, California 95616, USA. ICR compounds See ACRIDINES. IcsA protein See DYSENTERY and PROTEIN SECRETION (type IV systems). icteroanaemia (porcine) See EPERYTHROZOONOSIS. icterus Jaundice. ICTV International Committee on Taxonomy of Viruses. (cf. ICNV.) id reaction The formation of skin lesions at sites remote from a focus of infection; such lesions are commonly sterile, and they may represent a local HYPERSENSITIVITY response to the infection. If the infecting organism is e.g. Trichophyton the reaction is termed trichophytid. ID50 Infectious dose (50%): that dose of a given infectious agent which, when given to each of a number of experimental test systems or animals, brings about the infection of 50% of the systems/animals under given conditions. 385

IgD IgD Immunoglobulin D, an IMMUNOGLOBULIN present in very low concentrations in plasma; it occurs mainly as a surface receptor for antigen on the membranes of B LYMPHOCYTES. The IgD molecule (MWt ca. 175000; S20 W 7) contains delta HEAVY CHAINS, kappa or lambda LIGHT CHAINS, and ca. 12–13% carbohydrate. IgE Immunoglobulin E, an IMMUNOGLOBULIN found in minute quantities in plasma. The IgE molecule (MWt ca. 190000; S20 W 8) contains epsilon HEAVY CHAINS, kappa or lambda LIGHT CHAINS, and ca. 12% carbohydrate. IgE binds to basophils and mast cells via its Fc portion, causing degranulation in the presence of specific allergen and thus effecting a TYPE I REACTION; cytophilic activity is abolished e.g. by heating (56° C/3–4 hours). IgG Immunoglobulin G, the predominant IMMUNOGLOBULIN in plasma (ca. 9–16 mg/ml, 75% of total plasma Ig). The IgG molecule (MWt ca. 150000; S20 W 7) contains gamma HEAVY CHAINS, kappa or lambda LIGHT CHAINS, and ca. 3% carbohydrate. There are four subclasses – IgG1, IgG2, IgG3 and IgG4 – distinguished by differences in amino acid sequences and by serology; human IgG subclasses are numbered in order of their concentrations in plasma: IgG1 comprises ca. 65% of plasma IgG. IgG1 and IgG3 are bivalent COMPLEMENT-FIXING ANTIBODIES (half-life ca. 21 and 7 days, respectively) which are important e.g. as opsonins and antitoxins in extravascular regions as well as in the bloodstream; in humans, they can cross the placenta and are important in the protection of the fetus and neonate. (Efficient binding of complement component C1 appears to require an IgG doublet, i.e. two molecules side by side; a single IgG molecule binds C1 only weakly.) IgG antibodies generally appear to predominate in the secondary (anamnestic) humoral reponse to antigen. (See also ALLOTYPE.) IgG protease See e.g. ELASTASE. IgM (macroglobulin) Immunoglobulin M, a minor plasma IMMUNOGLOBULIN (comprising ca. 5–10% of total plasma Ig); phylogenetically, IgM is apparently the most primitive class of Igs. The IgM monomer (MWt ca. 180000) contains mu HEAVY CHAINS, kappa or lambda LIGHT CHAINS, and ca. 12% carbohydrate; monomeric IgM occurs as a surface receptor for antigen on the B LYMPHOCYTE membrane. The typical form of IgM is a pentamer (S20 W 19) in which the five monomers are arranged radially (Fc portions directed towards the centre) and connected via disulphide bonds, with a J CHAIN at the centre of the polymer; in the free (uncombined) form, an IgM antibody is therefore stellate, but pentameric IgM is sufficiently flexible to assume a spider-like conformation in order to combine with multiple-repeating antigens on a surface. (IgM antibodies are thus particularly good agglutinators of those antigens, e.g. bacteria, which display a pattern of repeated antigenic determinants.) IgM antibodies are COMPLEMENT-FIXING ANTIBODIES with a theoretical valency of 10. Maximum valency is generally exerted only with small haptens; with larger antigens the effective valency is often only 5. (It appears that an IgM antibody must bind antigen at more than one of its combining sites in order to be able to fix complement [Mol.Immunol. (1981) 18 863–868, cited in Book ref. 42, p. 647].) In man, IgM does not pass through blood vessel walls into the tissues, and does not cross the placenta; its half-life is ca. 5 days. IgM antibodies are often the first to be formed in the humoral response to antigen; the humoral response to THYMUS-INDEPENDENT ANTIGENS (such as purified pneumococcal polysaccharides) generally involves, almost exclusively, the formation of IgM antibodies. The Wassermann antibody (see WASSERMANN REACTION) and the rheumatoid factor (see RHEUMATOID ARTHRITIS) are largely or exclusively IgM antibodies.

IGS (mol. biol.) Internal guide sequence: see SPLIT GENE (b). IHF INTEGRATION HOST FACTOR. IkBa See CYTOKINES. IL Abbreviation for interleukin. See separate entries for INTERLEUKIN-1 (IL-1), INTERLEUKIN-2 (IL-2) etc. IL-1 INTERLEUKIN-1. IL-1g Syn. INTERLEUKIN-18. IL-2 INTERLEUKIN-2. ilarviruses (‘isometric labile ringspot viruses’; tobacco streak virus group) A group of tripartite ssRNA-containing PLANT VIRUSES which have a wide host range; transmission occurs via seeds and pollen and can readily occur mechanically. Type member: tobacco streak virus; other members include e.g. apple mosaic virus, Citrus leaf rugose virus, Citrus variegation virus, Prunus necrotic ringspot virus, spinach latent virus, Tulare apple mosaic virus. Virions: quasi-isometric, occasionally bacilliform; several types occur, differing in size (ca. 26–35 nm diam.) and in S20 W. Genome: three molecules of linear positive-sense ssRNA: RNA1 (MWt ca. 1.1 × 106 ), RNA2 (MWt ca. 0.9 × 106 ) and RNA3 (MWt ca. 0.7 × 106 ); the coat protein mRNA (‘RNA4’) is also encapsidated. RNAs 1, 2 and 3, together with coat protein or RNA4, are required for infectivity (cf. ALFALFA MOSAIC VIRUS). ileocaecal syndrome Syn. NEUTROPENIC ENTEROCOLITIS. Ilheus virus See FLAVIVIRIDAE. illegitimate name In NOMENCLATURE: a validly published name which contravenes any rule(s) of the relevant nomenclatural code. illegitimate recombination Fortuitous RECOMBINATION which occurs between DNA sequences which are non-homologous or which have very short regions of homology. In Escherichia coli illegitimate recombination is recA-independent and may be mediated by GYRASE: strands cleaved during gyrase action at different sites may undergo crossing over by the exchange of gyrase subunits covalently bound to the cut ends [model: PNAS (1983) 80 2452–2456]. imazalil An agricultural systemic ANTIFUNGAL AGENT, an imidazolyl derivative which acts as an inhibitor of sterol biosynthesis, thereby disrupting the cytoplasmic membrane in susceptible fungi. Imazalil is used – mixed with e.g. guazatine or thiophanate-methyl – as a seed treatment against many seedborne pathogens of cereals (e.g. Ustilago and Pyrenophora spp). It is also effective against Penicillium diseases of citrus fruits. imbricated Overlapping, like tiles on a roof. ImD unit See MICROCOMPLEMENT FIXATION. IMF INTERMEDIATE FILAMENT. imf phosphorylation See ELECTRON TRANSPORT PHOSPHORYLATION. Imhoff tank A large tank formerly widely used for SEWAGE TREATMENT. Essentially, crude sewage flows into a sludge settlement chamber located within a larger tank; sludge falls from a slot in the settlement chamber into the main digester compartment where it undergoes ANAEROBIC DIGESTION. The tank is vented for the escape of gases. IMI Imperial Mycological Institute, the former name of the Commonwealth Mycological Institute, Kew, UK. imidazole antifungal agents See AZOLE ANTIFUNGAL AGENTS. imipenem See THIENAMYCIN. immediate hypersensitivity (immunol.) HYPERSENSITIVITY mediated by humoral antibodies: see TYPE I REACTION, TYPE II REACTION, TYPE III REACTION, TYPE V REACTION (cf. DELAYED HYPERSENSITIVITY). Immediate hypersensitivity reactions typically occur within minutes or hours of contact with specific 386

immune globulin antigen; they are also referred to as immediate-type hypersensitivity reactions to include those which require hours or days to develop. immediate-type hypersensitivity See IMMEDIATE HYPERSENSITIVITY. Immedium filter See SEWAGE TREATMENT. immersion lens See RESOLVING POWER. immersion oil Cedarwood or synthetic oil (refractive index ca. 1.5) used with oil-immersion objectives (see RESOLVING POWER). In homogeneous immersion the immersion oil, objective lens, and cover-glass all have the same refractive index. Oil should be removed from the objective with a lens tissue immediately after use; unless otherwise recommended, a suitable solvent is 1,1,1trichloroethane, but benzene or xylene can be used. Prolonged contact with solvents may damage lens mountings. immobilization (1) (biotechnol.) Microbial, plant or animal cells, or macromolecules, may be ‘immobilized’ by attachment to solid structures, incorporation in gels etc for use in e.g. BIOCONVERSIONS (sense 1) – in some cases on an industrial scale. Various immobilized macromolecules are used e.g. in procedures involving affinity CHROMATOGRAPHY. Enzymes are immobilized because soluble enzymes are difficult to separate from substrates or products (and, hence, cannot be re-used in industrial processes), and most are unstable under conditions of use. The main methods of enzyme immobilization are: (a) Binding to a solid carrier or support. Supports used for covalent binding include e.g. cellulose, ceramic, glass, steel and synthetic polymers; usually, the support is ‘activated’ (see e.g. CYANOGEN BROMIDE), and the enzyme is then allowed to bind (commonly via its amino or carboxyl groups) to the activated support. The active site of the enzyme can be protected by allowing binding to occur in the presence of the enzyme’s substrate. Supports used for ionic binding include ion exchangers such as DEAE-cellulose. (b) Cross-linking with bifunctional reagents to form insoluble aggregates. Reagents used include GLUTARALDEHYDE (which binds enzymes via their amino groups), or diamines (e.g. hexamethylenediamine) which bind enzymes via their carboxyl groups after these groups have been ‘activated’ with carbodiimides; e.g., immobilized glucose isomerase is manufactured by treating pellets of homogenized cells of Bacillus coagulans with glutaraldehyde, yielding waterinsoluble aggregates containing glucose isomerase and other proteins. (c) Encapsulation. Enzymes are enclosed within LIPOSOMES or hollow fibres which are permeable to low-MWt substrates and products. (d) Entrapment within polymeric gels such as calcium ALGINATE, k-CARRAGEENAN and polyacrylamide. Enzymes are added to a solution of the polymer which is then gelled e.g. by the addition of a gelling agent. Leakage of enzymes from the gel may be counteracted by cross-linking them e.g. with glutaraldehyde. Entrapment is suitable primarily for bioconversion of low-MWt substrates which can diffuse through the gel. Immobilized enzymes are used for simple one-step or twostep bioconversions in which there is no need for regeneration of coenzymes. [Potential for immobilization of coenzymedependent enzymes: PTRSLB (1983) 300 335–367.] In some cases immobilization can improve the stability of enzymes which may otherwise be inadequate under operational conditions; e.g. immobilization of proteases inhibits their mutual degradation, and multipoint binding of an enzyme to its support helps to retain the conformational integrity of the enzyme – protecting it from inactivation by various denaturing agents (e.g. heat). Immobilized cells can be used for bioconversions which are not possible with isolated enzymes; the use of cells saves the cost

and labour of preparing purified immobilized enzymes. Cells can be immobilized by the methods used for enzymes (see above), but entrapment is the most commonly used method; gels used include e.g. agar, alginate, k-carrageenan, polyacrylamide, and polyurethane. Dead cells may be used for simple one-step or two-step reactions (provided they retain specific enzymic activity), but living cells are necessary for multistep transformations in which several enzymes act sequentially and/or in which there is a need for the regeneration of cofactors. Examples of the industrial use of dead immobilized cells include e.g. Escherichia coli in a k-carrageenan gel for the production of L-aspartic acid from ammonium fumarate, and ‘Brevibacterium flavum’ in a k-carrageenan gel for the production of L-malic acid from fumaric acid. High cell densities can be achieved with immobilized living cells. Thus, e.g., in one process used for the production of ethanol, Saccharomyces cerevisiae (‘S. carlsbergensis’) is immobilized in carrageenan, and ‘beads’ of the gel (containing 3.5 × 106 cells/ml) are incubated in a shaken nutrient medium for 60 hours: cell density rises to over 5 × 109 cells/ml – ca. 10 times higher than that possible in a conventional broth culture – with the yeast cells densely packed within the surface layer of each bead. When such beads are packed into a column and fed with a glucose-containing nutrient medium they produce ethanol efficiently for long periods of time. Other uses of immobilized living cells include the production of hydrogen from cells of Anabaena cylindrica bound to glass beads, and the production of an extracellular a-amylase by Bacillus subtilis immobilized in a polyacrylamide gel. [Book ref. 3, pp. 203–222, and PTRSLB (1983) 300 369–389 (cells); Book ref. 31, pp. 331–367 (enzymes); Science (1983) 219 722–727.] (2) The inhibition of MOTILITY in a microorganism – e.g. by a specific antiserum (see IMMOBILIZATION TEST). immobilization test Any test which involves the inhibition of MOTILITY in a microorganism. Immobilization tests can be used e.g. to detect specific antibodies (see e.g. TPI TEST) or organisms (e.g. a given strain of Vibrio cholerae may be identified by determining which types of specific antibody inhibit its motility). Antibodies may immobilize a motile organism e.g. by mediating the adhesion of flagella, or by promoting IMMUNE CYTOLYSIS. immune (1) (adj.) Refers to the state of IMMUNITY (sense 2 or 3). (2) (noun) See EPIDEMIOLOGY. immune adherence A phenomenon in which antigen–antibody complexes that have triggered COMPLEMENT FIXATION adhere firmly to receptors on phagocytes; the enhanced adhesion (which adds to that due to direct antigen–antibody–phagocyte interaction) is due mainly to component C3b. The phrase ‘immune adherence’ is sometimes used also to refer to the totality of pathogen–phagocyte adherence, i.e. including both antibody-mediated and complement-mediated adhesion. immune complex An antigen–antibody complex. Small, soluble (i.e. non-precipitating) immune complexes are formed e.g. under ANTIGEN EXCESS conditions. (See also TYPE III REACTION.) immune cytolysis The lysis of a cell which has been sensitized (SENSITIZATION sense 3) and which has triggered COMPLEMENT FIXATION; lysis may result directly or indirectly from the formation of a pore, in the membrane, created by the membrane attack complex. (cf. REACTIVE LYSIS.) immune deficiency-associated virus See AIDS. immune electron microscopy IMMUNOELECTRON MICROSCOPY. immune globulin Antiserum (or its immunoglobulin fraction) containing antibodies to a particular antigen or antigens. 387

immune haemolysis immune haemolysis IMMUNE CYTOLYSIS of erythrocytes. immune lysis Syn. IMMUNE CYTOLYSIS. immune response The response(s) of a person or animal to immunological contact with an antigen; such responses may involve e.g. priming (see PRIMED), ANTIBODY FORMATION, an ANAMNESTIC RESPONSE, a HYPERSENSITIVITY reaction, or IMMUNOLOGICAL TOLERANCE. (See also ANTIGENIC COMPETITION.) immune serum Syn. ANTISERUM. immune surveillance Syn. IMMUNOSURVEILLANCE. immune tolerance See IMMUNOLOGICAL TOLERANCE. immunity (1) A state characterized by the tendency of the body to reject, eliminate or otherwise counteract foreign (‘non-self’) or seemingly foreign materials, or organisms, on or within its tissues; in this (broadest) sense immunity includes AUTOIMMUNITY, HYPERSENSITIVITY and IMMUNOLOGICAL TOLERANCE as well as other forms of SPECIFIC IMMUNITY, and NON-SPECIFIC IMMUNITY. (2) The state of an individual who, having had prior contact with a given antigen, can react to further contact with that antigen more vigorously than can a non-immune individual; in this sense immunity includes all the (beneficial and harmful) manifestations of HUMORAL IMMUNITY and CELL-MEDIATED IMMUNITY, including HYPERSENSITIVITY. (3) (protective immunity; functional immunity) Relative insusceptibility to specific harmful agents (e.g. pathogens) involving only the beneficial effects of humoral immunity and/or cell-mediated immunity. immunity breakdown See COLICINS. immunity groups See e.g. COLICIN E. immunity protein See e.g. COLICIN PLASMID; COLICINS; KILLER FACTOR. immunization (1) Any procedure in which specific microorganisms and/or antigenic materials (see VACCINE), or pre-formed antibodies, are introduced into the body in order to bring about specific protective IMMUNITY. (cf. INOCULATION (2) and VACCINATION.) Stimulation of the body’s own immune response (by administration of a vaccine) is referred to as active immunization; the (parenteral) administration of pre-formed antibodies is called passive immunization (see also PASSIVE IMMUNITY). (2) The administration of antigen to elicit any form of SPECIFIC IMMUNITY. (See also ISOIMMUNIZATION; HETEROIMMUNIZATION; NON-SPECIFIC IMMUNIZATION.) immunoadjuvant See ADJUVANT (1). immunoassay Any procedure in which the specificity of the antigen–antibody reaction is used for detecting and quantifying antigens, antibodies, or substance(s). (See e.g. ELISA; ERYTHROIMMUNOASSAY; ENZYME IMMUNOASSAY; IMMUNORADIOMETRIC ASSAY; PREGNANCY TEST; RADIOIMMUNOASSAY.) immunoblotting See BLOTTING. immunocompromised Unable to exhibit a normal immune response. immunoconglutinins Autoantibodies homologous to certain bound components of COMPLEMENT, particularly C3b; titres of serum immunoconglutinins are raised in long-term autoallergic conditions and in some diseases of microbial aetiology. Immunoconglutinins possibly play a role in the agglutination and phagocytosis of small, C3b-containing complexes. (cf. CONGLUTININ.) immunocyte Any functional cell of the immune system. immunocyte adherence technique (rosette technique) A method used e.g. for detecting cells which form specific antibodies. When such cells are incubated with homologous particulate antigen (or with erythrocytes coated with homologous soluble antigens) the antigenic particles adhere to specific receptor sites on the surfaces of the antibody-forming cells, forming rosettes. (See also PROTEIN A.)

immunodeficiency The inability to respond with a normal immune response to antigenic stimulation. (See also e.g. AIDS.) immunodepression Syn. IMMUNOSUPPRESSION. immunodiffusion See GEL DIFFUSION. immunodominant See DETERMINANT and ANTIGENIC COMPETITION. immunoelectron microscopy A procedure used e.g. for locating particular antigens in cells or tissues. Essentially, the given antigen is isolated and an antiserum is raised against it. The homologous antibodies are labelled with e.g. FERRITIN and then allowed to combine with the antigen in the cells or tissue; on examination by transmission ELECTRON MICROSCOPY the location of the given antigen is indicated by the ferritin label. (The use of ferritin in this way is called the immunoferritin technique.) (cf. IMMUNOSORBENT ELECTRON MICROSCOPY; see also IMMUNOGOLD TECHNIQUE.) immunoelectrophoresis (IEP) Any procedure in which antibodies (or other serum proteins) and/or antigens are subjected to ELECTROPHORESIS prior to their detection, characterization, or quantification (e.g. by means of specific antigen–antibody precipitation or staining). In one form of IEP the serum (or other) sample is first subjected to electrophoresis in a strip of agarose (or other) gel. This separates components into discrete zones – each zone containing one or more proteins characterized by a specific electrophoretic mobility. (Some proteins migrate in an unexpected direction – see ELECTROENDOSMOSIS.) A rectangular slot (‘trough’), cut into the gel strip parallel to the line of electrophoretic migration, is filled with antiserum containing antibodies to some or all of the proteins in the sample; the proteins and their homologous (and/or cross-reacting) antibodies diffuse through the agar and form lines or arcs of precipitate where they meet in OPTIMAL PROPORTIONS (see GEL DIFFUSION). (See also CHARGE-SHIFT IMMUNOELECTROPHORESIS; COUNTERCURRENT IMMUNOELECTROPHORESIS; ROCKET IMMUNOELECTROPHORESIS; TWO-DIMENSIONAL ELECTROPHORESIS.) immunoferritin technique See IMMUNOELECTRON MICROSCOPY. immunofluorescence The use of a fluorescent antibody (i.e. antibody conjugated with a FLUOROCHROME such as FITC, FLUORESCEIN, or RHODAMINE isothiocyanate) for the detection and/or quantification of a specific antigen (or antibody). In the simplest (direct) immunofluorescence techniques, used to detect antigen, the specimen (tissue section, smear etc) is exposed to the conjugate (i.e. dye-linked antibody) for an appropriate time, washed free of conjugate, and examined by fluorescence MICROSCOPY; antigens homologous to the fluorescent antibodies are readily identified by regions of fluorescence in the specimen. In the indirect immunofluorescence technique (e.g. the indirect fluorescent antibody test, IFAT) the presence of a given antigen can be determined by first exposing the specimen to unstained antibodies (e.g. a serum containing antibodies homologous to the given antigen); the specimen is then washed free of uncombined antibodies, exposed to fluorescent anti-Ig antibodies, washed, and examined by fluorescence microscopy. Any antigen–antibody combination on the specimen can thus be detected by the presence of fluorescent antibodies (which bind to the unstained antibodies); if particular antigens are known to be present in the specimen, the test can be used to detect homologous antibodies in the serum. Another type of indirect immunofluorescence technique is referred to as the SANDWICH TECHNIQUE. In all immunofluorescence techniques adequate controls are necessary to preclude an interpretation based on the non-specific localization of conjugate, and to take into account any primary FLUORESCENCE. 388

immunoradiometric assay immunoliposome See LIPOSOME. immunological drift Syn. ANTIGENIC DRIFT. immunological paralysis IMMUNOLOGICAL TOLERANCE – particularly that induced by pneumococcal polysaccharides. immunological surveillance Syn. IMMUNOSURVEILLANCE. immunological tolerance Inability to respond normally to a given antigen (by humoral and/or by cell-mediated mechanisms) as a consequence of prior exposure to that antigen; unrelated antigens may elicit normal responses in the same individual. (cf. SELF TOLERANCE.) Tolerance may be total (i.e. no detectable response to antigen) or may involve e.g. failure to produce certain class(es) of antibody or some type(s) of immune response. Failure to react normally to some antigens may be beneficial in that harmful HYPERSENSITIVITY reactions may be avoided. The extent, duration, and type of acquired tolerance is influenced e.g. by the size of dose of the inducing antigen (the toleragen), the nature of the antigen, the route of administration, and the state of immunological maturity of the individual when tolerance is induced; the induction of tolerance is inhibited e.g. by adjuvants and is favoured e.g. by ANTIGENIC COMPETITION and by non-specific immunosuppression. Typically, thymus-dependent antigens (e.g. proteins) can induce tolerance when administered in doses higher than the normal immunizing dose (high-zone tolerance) or lower than the normal immunizing dose (low-zone tolerance); in high-zone tolerance both specific B cell and T cell clones are unresponsive (clonal deletion), while in low-zone tolerance only the helper T cell clone is unresponsive. Thymus-independent antigens usually induce only high-zone tolerance. Direct access of antigens to the gastrointestinal tract favours the induction of tolerance (see also SULZBERGER–CHASE PHENOMENON). In general, tolerance to a given antigen is more readily induced in the fetus or neonate than in the adult, and in a naive subject than in a primed one. The duration of tolerance may be extended by repeated administration of antigen. Diverse mechanisms of tolerance induction have been suggested (including e.g. enhancement of suppressor T cell activity), and different types of tolerance may involve different mechanisms. Exposure of immature B lymphocytes to specific antigen or to anti-Ig makes them subsequently unresponsive (i.e., unable to secrete antibody) when exposed to specific antigen (clonal abortion); this suggests a reason why tolerance can be induced more easily in the fetus or neonate than in adults. immunological unresponsiveness (1) Syn. IMMUNOLOGICAL TOLERANCE. (2) Inability, or reduced ability, to respond to antigens in general, due e.g. to IMMUNOSUPPRESSION. immunomagnetic separation See DYNABEADS. immunomodulation Specific or generalized alteration of the immune response (see IMMUNOSTIMULATION; IMMUNOSUPPRESSION; IMMUNOLOGICAL TOLERANCE). immunopathogenesis The development of pathological effects as a direct result of the immune response. immunoperoxidase method Any method in which antibodyconjugated, or otherwise complexed, peroxidases (e.g. horseradish peroxidase) are used to locate specific antigens on cells or tissues (see e.g. ABC IMMUNOPEROXIDASE METHOD and PAP TECHNIQUE). immunopotentiation (1) Syn. IMMUNOSTIMULATION. (2) Nonspecific immunostimulation. immunoprecipitable Capable of being precipitated by homologous antibodies. immunoradiometric assay A highly sensitive IMMUNOASSAY by which specific antigens are quantified using radioactive antibodies – which may be prepared as follows. Antigen is adsorbed

(See also FLOW MICROFLUOROMETRY.) immunogen (1) Syn. ANTIGEN. (2) An antigen which can stimulate protective immunity. immunogenicity The capacity to function as an IMMUNOGEN. (Hence adj. immunogenic.) immunoglobulin superfamily A category of CELL ADHESION MOLECULES characterized by a molecular structure homologous to that of immunoglobulins – i.e. a number of immunoglobulin domains, each containing an intra-domain disulphide bond. These molecules are involved e.g. in calcium-independent cell–cell adhesion and antigen-specific interaction. The first member of the family to be isolated was the neural cell adhesion molecule (NCAM) which appears early in ontogeny and is important e.g. in the development of the central nervous system; binding is homophilic, i.e. NCAM binds to NCAM – in contrast to most members of the superfamily which bind to dissimilar molecules (i.e. heterophilic binding). Other members are important in the immune system – e.g. the T CELL RECEPTOR and the CD4 and CD8 molecules. Interactions between T cells and other cells also involve the leukocyte function-associated antigens LFA-2 (= CD2) and LFA-3 (= CD58); CD2 occurs on T cells, while CD58 occurs on many types of cell. CD2 and CD58 bind to one another. (N.B. LFA-1 is a member of the integrin family: see CD11a/CD18.) The intercellular adhesion molecules (ICAMs) have important roles in cell–cell adhesion. ICAM-1 (= CD54), ICAM-2 (CD102) and ICAM-3 (CD50) – widely distributed (e.g. on endothelium, monocytes, lymphocytes) – bind to integrin ligands (see CD11a/CD18). In at least some circumstances, cell-surface expression of ICAMs can be upregulated or down-regulated. (See also CD31 and CD106.) immunoglobulins (Igs) A class of proteins present e.g. in plasma, colostrum, tears and other body fluids; all antibodies are immunoglobulins (see ANTIBODY and ANTIBODY FORMATION). The (monomeric) form of an immunoglobulin consists of four polypeptide chains: two identical HEAVY CHAINS and two identical LIGHT CHAINS which are linked by interchain disulphide bonds to form a Y-shaped macromolecule. The two heavy chains are adjacent for part of their length, their N-terminal ends diverging (at the HINGE REGION) to form the two limbs of the Y; two or more disulphide bonds connect the heavy chains at the hinge region. One light chain runs alongside each of the two limbs of the Y, and is attached to it by a disulphide bond. The distal (N-terminal) end of each limb of the Y is, compositionally, a highly variable region – VH and VL referring to the so-called variable (distal) DOMAINS (V regions) of the heavy and light chains, respectively. The composition of the rest of the molecule is relatively constant, and is therefore termed the constant region (C region). The C region of each heavy chain comprises several DOMAINS which are designated CH 1, CH 2 etc (numbering from the V region end), while the constant region of the light chain consists of a single domain designated CL . Certain enzymes, e.g. PAPAIN, cleave the Ig monomer at the hinge region, producing two identical FAB PORTIONS and an FC ′ PORTION. Pepsin cleaves monomeric Ig to form an F(ab )2 portion (q.v.). Five Ig classes are distinguished: see entries for IgA, IgD, IgE, IgG and IgM. [Book ref. 42, pp. 131–219.] immunogold technique A form of IMMUNOELECTRON MICROSCOPY in which the specific antibodies (or PROTEIN A molecules) are complexed with gold prior to use – the gold serving as an electron-dense marker. 389

immunorecessive of the growth medium due to the effects of metabolism. [JAB (1982) 53 423–426.] imperfect stage (mycol.) See ANAMORPH. impetigo A superficial, highly infectious skin disease, common in children, caused by Streptococcus pyogenes and/or Staphylococcus aureus. In the streptococcal form, spreading, inflamed pustules develop, rupture, and form thick brownish-yellow crusts; lesions may be secondarily infected by staphylococci. In the staphylococcal form (bullous impetigo) the lesions contain watery fluid rather than pus, and a thin crust forms over the centre of the lesion. Bullous impetigo occurs most commonly in very young infants; superinfection with streptococci is rare. Chemotherapy: e.g. oral penicillin (for streptococcal impetigo) or erythromycin. [Book ref. 17, pp. 341–346.] impinger See AIR. IMS See DYNABEADS. IMVEC tests IMVIC TESTS plus the EIJKMAN TEST. IMViC tests Tests used for the identification of bacteria e.g. of the family Enterobacteriaceae: INDOLE TEST, METHYL RED TEST, VOGES–PROSKAUER TEST, CITRATE TEST. (cf. EIJKMAN TEST.) in-block staining See ELECTRON MICROSCOPY (a). in situ gene amplification See IN SITU PCR. in situ hybridization See PROBE. in situ PCR PCR-based amplification of a target inside intact cells. The cells may be initially attached to glass slides (e.g. with AAS in acetone) and are fixed (e.g. with a formalin-based solution). The cells are then treated (permeabilized ) so as to allow entry of PCR reagents without encouraging the exit of PCR products. The reaction mixture is added to the cell layer (or tissue section), and is held in place with a cover slip. Temperature cycling may be carried out in a specialized form of THERMOCYCLER in which each slide is processed in a close-fitting slot that ensures good thermal contact (e.g. the GeneAmp In situ PCR System 1000; PerkinElmer). After amplification, another phase of fixation promotes intracellular retention of the products. Detection of products may be direct or indirect. Direct detection involves the use of labelled nucleotides or primers in the reaction mixture, and detection of the label histochemically. One disadvantage of this approach is that all amplified products will be labelled – even those resulting from mis-priming; as a consequence, the specificity of the assay is reduced. Improved specificity is obtained by the indirect mode of detection which involves the use of a labelled probe that is complementary to an internal sequence in the amplicon; the use of such a probe is equivalent to adding a stage of in situ hybridization (ISH), and procedures which involve indirect detection of products in this way have been referred to as PCR-ISH (‘in situ PCR’ being reserved for those procedures involving direct detection of products). Collectively, in situ PCR and PCR-ISH have been referred to as in situ gene amplification (IS-GA) [RMM (1997) 8 157–169]. This approach has been widely used for studying virusinfected cells, and may be particularly useful e.g. for those viruses which remain latent in tissues in small numbers. One early study detected intracellular lentiviral DNA [PNAS (1990) 87 4971–4975]. PCR-ISH has been used e.g. in studies on g-herpesvirus type 8 [AJP (1997) 150 147–153]. in vitro complementation assay An assay based on the COMPLEMENTATION of a defective (mutant) protein by an active (wildtype) form of that protein; such assays are used e.g. to determine which of several proteins is/are involved in a particular process. For example, to identify a protein involved in DNA synthesis, a cell-free DNA-synthesizing system is initially prepared

to an inert carrier (e.g. cellulose) and exposed to purified immunoglobulins obtained from an antiserum containing the homologous antibody; uncombined antibodies are removed by washing, and the combined antibodies are radiolabelled (e.g. with 125 I). The radioactive antibodies are then eluted for use in the assay. In one form of assay, excess radioactive antibody is added to the sample containing antigen at an unknown concentration; the reaction mixture is then exposed to fresh, cellulosebound antigen which adsorbs the uncombined antibodies and permits their separation from the reaction mixture. The amount of combined antibody can then be measured by determining the level of radioactivity remaining in the reaction mixture; this allows the concentration of antigen in the sample to be determined from a previously prepared standard curve (radioactivity versus antigen concentration). (cf. RADIOIMMUNOASSAY.) immunorecessive See DETERMINANT. immunosilent See DETERMINANT. immunosorbent assay Any IMMUNOASSAY in which antigen or antibody is immobilized by adsorption to a solid surface – see e.g. ELISA. immunosorbent electron microscopy (ISEM) ELECTRON MICROSCOPY in which particulate antigens (e.g. specific viruses) are detected or examined by first complexing them with homologous antibodies; prior to antigen–antibody interaction the antibodies may be e.g. fixed to an electron microscope grid (Derrick’s method, antibody-coated grid technique, A-CGT), adsorbed to a PROTEIN A-coated grid (Shukla’s method, protein A-coated grid technique, PA-CGT), or adsorbed directly to the protein A of cells of Staphylococcus aureus (protein A-coated bacteria technique, PA-CBT). [Review: AVR (1984) 29 169–194.] (cf. IMMUNOELECTRON MICROSCOPY.) immunostaining The staining of a specific antigen or structure by any method in which the stain (or stain-generating system) is complexed with specific antibody (e.g. ABC IMMUNOPEROXIDASE METHOD). immunostimulation Specific or non-specific potentiation of the immune response – e.g. by the administration of a VACCINE or by the use of an ADJUVANT. (cf. IMMUNOPOTENTIATION.) immunosuppression (immune suppression) Complete or partial suppression of normal IMMUNE RESPONSES – either in respect of specific antigen(s) (see also IMMUNOLOGICAL TOLERANCE) or in respect of all antigens (generalized suppression). Immunosuppression can be induced e.g. by ionizing radiation; specific antimetabolites (e.g. the folic acid antagonist methotrexate); a variety of antimitotic/antitumour agents (e.g. 6-mercaptopurine, prednisone, CYCLOSPORIN A, cyclophosphamide, azathioprine); antilymphocyte serum. Immunosuppression induced by radiation or by drugs tends to be generalized. immunosurveillance The continual monitoring of the tissues for abnormal antigens (e.g. on tumour cells) by cells of the immune system. immunotoxin An antibody–toxin conjugate intended to destroy specific target cells (e.g. tumour cells) which bear antigens homologous to the antibody. [Anti-CD22 immunotoxin BL22, which uses a fragment of EXOTOXIN A, in chemotherapy-resistant HAIRY-CELL LEUKAEMIA: NEJM (2001) 345 241–247.] Imotest A form of TUBERCULIN TEST in which a disposable plastic unit is used. The tuberculin is contained in a sealed plastic tube which is first broken and then squeezed to inoculate the nine points used to penetrate the skin. IMP Inosine 5′ -monophosphate: see Appendix V(a). impactor See AIR. impedimetry A technique in which microbial growth and activity are measured in terms of changes in the electrical impedence 390

incompatibility incompatibility (in plasmids) The inability of PLASMIDS to coexist, stably, within the same cell when they have similar or identical systems for replication (see PLASMID) and/or PARTITION. Two incompatible plasmids which occupy the same cell will (in the absence of a selective pressure for both plasmids) tend to segregate to different cells during cell division. The stable intracellular co-existence of one plasmid with another requires that each plasmid be able to control, independently of the other, its own replication/partition such that it can establish and maintain a stable COPY NUMBER; the inability of a given plasmid to maintain a stable copy number in the presence of another plasmid is the characteristic feature of incompatibility. In many cases, incompatibility arises from the synthesis of plasmid-encoded trans-acting elements involved in the negative control of plasmid replication. Since plasmids with identical replication systems form identical trans-acting elements, the elements synthesized by one plasmid will affect the replication of other plasmids (in the same cell) which have an identical replication system. In this case, plasmid replication initially occurs randomly – e.g., two (incompatible) plasmids will each have an equal chance of being replicated. Once replicated, however, a plasmid of one type will be present at a higher copy number and will then be more likely to be involved in subsequent rounds of replication; this effect tends to be cumulative and to give rise to progeny cells that contain only one type of plasmid (‘homoplasmid segregants’). In plasmids which have similar but not identical replication systems, incompatibility may result in the preferential exclusion of one particular plasmid; for example, in a cell containing certain derivatives of the COLE1 PLASMID and of plasmid pMB1, the ColE1 derivative is rapidly excluded – possibly owing to differential sensitivity of the two plasmids to RNA I. (See also DISLODGEMENT and ONE-WAY INCOMPATIBILITY.) In a number of plasmids the negative control elements which govern incompatibility are small RNA molecules: see e.g. RNA I under COLE1 PLASMID, and CopA under R1 PLASMID. In the pT181 family of Staphylococcus aureus plasmids, too, replication is regulated by negative control elements (countertranscripts – see ANTISENSE RNA); however, in the pT181 family of plasmids incompatibility is not governed by such elements because the negative control elements of different plasmids in this group are not interchangeable. Among pT181 plasmids incompatibility is due to the existence of a common (interchangeable) Rep protein (an initiator protein which promotes replication by binding to the origin) [MGG (1986) 204 341–348]. Incompatibility and the classification of plasmids. The expression of incompatibility or compatibility between plasmids provides a useful criterion for classifying them. Thus, plasmids are classified into so-called incompatibility groups (Inc groups) in such a way that all the plasmids in a given Inc group express mutual incompatibility. Inc groups exist e.g. for plasmids which occur in enterobacteria, and separate Inc groups exist for plasmids which occur in other bacteria; some (‘promiscuous’) plasmids can occur e.g. in both enterobacteria and Pseudomonas spp, and some of these plasmids have been allocated to an Inc group in both the enterobacterial and pseudomonad grouping schemes. Enterobacterial Inc groups are designated by the prefix ‘Inc’ followed by a letter and, sometimes, by a Roman numeral or a Greek letter – e.g. IncFII, IncIa. The letter (e.g. F, I) indicates the type of conjugation system specified by the TRANSFER OPERON; thus, e.g. an IncF plasmid specifies a conjugative system like that of the F PLASMID or of an F-like plasmid, and encodes either F pili or F-like pili (see PILI). The Roman

from cells which have a temperature-sensitive mutation in a gene essential for DNA synthesis; such a system can synthesize DNA at permissive temperatures but not at restrictive temperatures. Proteins purified from a wild-type strain of the same species can then be added, separately, to the system to determine which of them can restore DNA-synthesizing activity at restrictive temperatures. in vivo expression technology See IVET. Inaba variant See VIBRIO (V. cholerae). inactivated serum Serum which has been heated to 56° C for 30 min; heating inactivates COMPLEMENT in the serum. inactivated vaccine (killed vaccine) Any VACCINE consisting of microorganisms which have been treated (e.g. with formalin) so that they are no longer capable of multiplying, although their PROTECTIVE ANTIGENS remain effective. (See e.g. SALK VACCINE; SEMPLE VACCINE.) inactivation (of a microorganism) (1) The killing of a microorganism. (2) The temporary (reversible) inhibition of growth (or other activity) of a microorganism. inactone See GLUTARIMIDE ANTIBIOTICS. inaequihymeniiferous See LAMELLA. Inc group See INCOMPATIBILITY. incB locus See F PLASMID. IncC group See INCOMPATIBILITY. incC locus See F PLASMID. incertae sedis Of uncertain taxonomic position. IncF groups See INCOMPATIBILITY. IncI groups See INCOMPATIBILITY. incident light microscopy See MICROSCOPY (e) and (g). inclusion blennorrhoea See OPHTHALMIA NEONATORUM. inclusion bodies (‘inclusions’) Discrete structures of various types present (normally or abnormally) within cells. In virology, the term generally refers to those structures which develop in certain virus-infected cells; such structures consist of virions and/or viral components and/or cellular material, and may be characteristic in form and location for a given type of virus. (See also CYTOPATHIC EFFECT; GUARNIERI BODIES; NEGRI BODIES; POLYHEDRA; VIROPLASM.) In bacteriology, the term may refer to structures within a bacterial cell (e.g. granules of GLYCOGEN, POLY-b-HYDROXYBUTYRATE or POLYSULPHATE; ‘hydrocarbon inclusions’ (see HYDROCARBONS); CARBOXYSOMES; GAS VACUOLES; R BODY) or to bacterial cells within a (parasitized) eukaryotic host cell (see e.g. ANAPLASMA and CHLAMYDIA). (See also OVERPRODUCTION.) inclusion body hepatitis A POULTRY DISEASE apparently caused by certain strains of AVIADENOVIRUS (e.g. the ‘Tipton’ strain). The liver of an infected bird is enlarged, yellowish, with haemorrhagic patches; haemorrhages may also occur in the muscles. The disease may be associated with INFECTIOUS BURSAL DISEASE VIRUS infection. inclusion body rhinitis A common, generally mild disease of young pigs, caused by suid herpesvirus 2 (see BETAHERPESVIRINAE). Infection occurs by inhalation; symptoms: e.g. sneezing, nasal discharge etc. The disease may become generalized, resulting in anaemia and sudden death. inclusion conjunctivitis In adults: CONJUNCTIVITIS caused by Chlamydia trachomatis, commonly serotype D, E, F, G, H, I, J or K; if untreated, the disease (which is also called paratrachoma) typically resolves spontaneously after some months. (cf. TRACHOMA.) In newborn infants: see OPHTHALMIA NEONATORUM. IncN group See INCOMPATIBILITY. 391

incompatible incubation period (med., vet.) The time interval between INFECTION (sense 1), or e.g. exposure to a TOXIN, and the appearance of the first symptoms of disease. (cf. PREPATENT PERIOD.) incubator See INCUBATION. IncX group See INCOMPATIBILITY. independent assortment (genetics) During e.g. MEIOSIS: the chance distribution of unlinked genes (see LINKAGE) among progeny cells. Thus, e.g., if the (diploid) parent cell contained the unlinked allelic pairs A/a and Z/z, any one of the four possible allele combinations (A and Z, A and z, a and Z, a and z ) may occur, with equal probability, in a given (haploid) progeny cell. indicator (pH) See PH INDICATOR. indicator organism Any organism whose presence and/or numbers serve to indicate the condition or quality of a material or environment. For example, in studies on faecal pollution in rivers, counts of the faecal bacteria Escherichia coli and Enterococcus faecalis are often used to indicate the degree of sewage pollution at given sites. The same organisms are also used for testing the efficiency of disinfection in treated drinking water, their presence in treated water supplies indicating a failure of the treatment process or contamination by sewage effluent subsequent to treatment. These organisms are used as indicators because they are common intestinal bacteria: their presence in water signals the potential presence of enteric pathogens. Water samples are not routinely tested for each of the (many) different types of enteric pathogen because, even in sewage-contaminated water, a given pathogen may occur only intermittently. Moreover, in sewage-contaminated water the indicator bacteria greatly outnumber pathogens so that they permit detection of very low levels of faecal pollution. Endospores of Clostridium perfringens, which remain viable for long periods of time, have been used to indicate previous contamination. Bifidobacterium spp may specifically indicate human faecal pollution [JAB (1983) 55 349–357], while faecal pollution from human and animal sources may be differentiated by differences in the antibiotic resistance patterns of ‘faecal streptococci’ [AEM (1996) 62 3997–4002]. Traditional tests for faecal indicator bacteria include the MULTIPLE-TUBE METHOD (for E. coli ) and membrane FILTRATION for FAECAL STREPTOCOCCI. Indicator organisms are also monitored in the assessment of food-handling conditions/hygiene [indicator organisms in meat: J. Food Protect. (1984) 47 672–677]. (See also SAPROBITY SYSTEM and lichens and pollution in the entry LICHEN.) indigoidine See ERWINIA (E. chrysanthemi ). indinavir See ANTIRETROVIRAL AGENTS. indirect agglutination Syn. PASSIVE AGGLUTINATION. indirect fluorescent antibody test (IFAT) See indirect IMMUNOFLUORESCENCE. indirect immunofluorescence See IMMUNOFLUORESCENCE. individual quick blanch (IQB) In the preparation of certain foods for CANNING: blanching by exposure of individual items of food to steam for a short period of time. indole 3-acetic acid See AUXINS. indole test An IMVIC TEST used to determine the ability of an organism to produce indole from tryptophan [see Appendix IV(f)]. The organism is grown in PEPTONE WATER or TRYPTONE WATER at 37° C. (N.B. The presence of carbohydrate (which may repress TRYPTOPHANASE) or nitrite in the medium can give ´ false-negative results.) Test procedures vary. (a) KOVACS’ INDOLE REAGENT (0.5 ml) is added to ca. 5 ml of e.g. a 48-hour culture with gentle shaking; the reagent forms a floating layer which,

numeral or Greek letter indicates a particular type of plasmid replication system; thus e.g. IncFI and IncFII plasmids have different replication systems (i.e., they are compatible) though they specify similar conjugation systems. Some examples of enterobacterial Inc groups are given below. IncFI includes the F PLASMID, the COLICIN PLASMID ColV-K94, and the R PLASMID R386. IncFII includes the R1 PLASMID, R6 and R100. IncIa (sometimes written IncI1 or IncI1 ) includes ColIb-P9, the delta plasmid (see DELTA), and R64. IncIg includes R621a. IncN includes N3, R46, and R269N-1. IncX includes the R6K PLASMID. Pseudomonas Inc groups are designated IncP-1 to IncP-13, the numbers referring to each of the 13 different types of replication system. The conjugation systems of Pseudomonas plasmids are less well known than those of enterobacterial plasmids, but the pili encoded by Pseudomonas plasmids have been characterized. [Pili encoded by Pseudomonas plasmids: JGM (1983) 129 2545–2556; Pseudomonas R plasmids: Book ref. 198, pp. 265–293.] Some of the Pseudomonas Inc groups are given below. IncP-2 includes the CAM PLASMID, the OCT PLASMID, and the R plasmid pMG1. IncP-6 includes the R plasmid Rms149. IncP-7 includes Rms148. IncP-8 includes plasmid FP2 (which encodes resistance to mercury). IncP-9 includes R2, the SAL PLASMID, and the TOL PLASMID. IncP-10 includes R91. IncP-11 includes RP8 and R151. IncP-12 includes R716. IncP-13 includes pMG25. Shared enterobacterial and pseudomonad Inc groups. Some of the shared groups are given below, the enterobacterial Inc group being given first. IncC (≡ IncP-3) includes R55. IncP (≡ IncP-1) includes R68, R751, RK2, RP1 and RP4. IncQ (≡ IncP-4) includes RSF1010. (A plasmid apparently related to this group, pFM739, has been isolated from Neisseria sicca [JGM (1986) 132 2491–2496].) incompatible (non-compatible) (plant pathol.) Refers to an interaction between a plant and a microorganism (e.g. an avirulent strain of a pathogen) which does not result in the development of disease in the plant. (cf. COMPATIBLE.) incomplete antibodies (1) Syn. BLOCKING ANTIBODIES (sense 1). (2) FAB PORTIONS. incomplete Freund’s adjuvant See FREUND’S ADJUVANT. IncP groups See INCOMPATIBILITY. IncQ group See INCOMPATIBILITY. incubation The maintenance of e.g. inoculated media or other types of material at a particular ambient temperature over a period of hours, days, weeks, or longer; the purpose of incubation is to provide conditions suitable for growth etc. Incubation is commonly carried out within closed, thermally insulated, thermostatically controlled chambers (incubators) or within vessels suspended in a WATER BATH; refrigerated incubators maintain the lower range of temperatures. Specialized incubation permits control of humidity, light, radiation etc as well as temperature. (cf. PHYTOTRON.) Cultures or specimens are sometimes left outside the incubator, i.e., they are exposed to the (often variable) conditions within the laboratory – a procedure known as ‘incubation at room temperature’. 392

infectious bronchitis extracellular CELLULASES) can use lignocellulose without prior hydrolysis, but the potential of this organism for ethanol production is limited by its poor tolerance of ethanol. On hydrolysis, most usable polysaccharides yield mainly hexoses – from which ethanol can be formed as a major product by various yeasts (including e.g. species of Candida, Kluyveromyces, Saccharomyces and Schizosaccharomyces) and by some bacteria (e.g. Zymomonas mobilis). The hydrolysis of HEMICELLULOSES yields significant quantities of PENTOSES, e.g. xylose; some organisms (e.g. Fusarium oxysporum) can convert xylose to xylulose, and can ferment the latter to ethanol via reactions of the HEXOSE MONOPHOSPHATE PATHWAY and the EMBDEN–MEYERHOF–PARNAS PATHWAY. Certain other organisms (e.g. Candida tropicalis, Pachysolen tannophilus) can also form ethanol from xylose, while a number of organisms (e.g. Saccharomyces, Schizosaccharomyces spp) can form ethanol from xylulose. A strain of Paecilomyces can give good yields of ethanol from a range of hexoses and pentoses [Nature (1986) 321 887–888]. industrial microbiology For examples of microorganisms and/or microbial products used on an industrial or commercial scale see e.g. AGAR, ALCOHOLIC BEVERAGES, ALGINATE, ASCORBIC ACID, BIOLOGICAL CONTROL, BIOMIMETIC TECHNOLOGY, BIOPOL, CARRAGEENAN, CITRIC ACID, COCOA, COFFEE, DAIRY PRODUCTS, DEXTRANS, DIATOMACEOUS EARTH, ENZYMES, ERGOT ALKALOIDS, FERMENTED FOODS, FUNORAN, FURCELLARAN, GELLAN GUM, GLUCONIC ACID, GLUTAMIC ACID, INDUSTRIAL ALCOHOL, INTERESTERIFICATION, KELP, LEACHING, MUSHROOM (senses 3 and 4), OVERPRODUCTION, RETTING, RIBOFLAVIN, SILAGE, SINGLE-CELL PROTEIN, STEROID BIOCONVERSIONS, VINEGAR, VITAMIN B12 , XANTHAN GUM and ZEARALENONE. infant botulism See BOTULISM (a). infantile gastroenteritis See EPEC. infantile paralysis Syn. POLIOMYELITIS. infection (1) The initial entry of a pathogen into a host. (2) The condition in which a pathogen has become established in or on the cells or tissues of a host; such a condition does not necessarily constitute or lead to disease. (3) Synonymous with disease of microbial aetiology. (See also CATHETER-ASSOCIATED INFECTION and TRANSFUSION-TRANSMITTED INFECTION.) (4) The establishment of a microbial symbiont in a host organism (see e.g. ROOT NODULES). infection-associated haemophagocytic syndrome (IAHS) See HAEMOPHAGOCYTIC SYNDROME. infection court (plant pathol.) The site at which a pathogen or parasite initiates infection of a plant (e.g. a wound). infection immunity Syn. PREMUNITION. infection peg See APPRESSORIUM. infection thread See ROOT NODULES. infectious abortion (vet.) See e.g. BRUCELLOSIS, CAMPYLOBACTERIOSIS, ENZOOTIC ABORTION. infectious ascites (of fish) See INFECTIOUS DROPSY. infectious bovine keratoconjunctivitis See INFECTIOUS KERATITIS. infectious bovine rhinotracheitis (red nose) A highly infectious CATTLE DISEASE caused by strains of bovine herpesvirus 1 (see HERPESVIRIDAE). (Rarely, pigs may be affected.) Infection occurs mainly by droplet inhalation. Incubation period: 3–7 days or longer. Onset is sudden, with anorexia, fever, necrotic lesions on the mucous membranes of the nasal septum, serous discharge from the eyes and nose, increased salivation etc; sudden death may result from obstructive bronchiolitis. Abortion is a common sequel. [Book ref. 33, pp. 798–804.] infectious bronchitis See AVIAN INFECTIOUS BRONCHITIS.

in a positive test (i.e. indole produced), becomes pink or red. (b) Xylene (ca. 1 ml) is added to ca. 5 ml of e.g. a 48-hour culture with vigorous shaking (to extract the indole). EHRLICH’S REAGENT (ca. 0.5 ml) is then allowed to run down the side of the slanted tube and forms a layer beneath the (floating) xylene; in a positive test a red colour develops in the reagent layer. (c) An oxalic acid-impregnated paper strip is inserted between the tube and stopper before incubation; during incubation (up to 7 days) indole (volatile at 37° C) reacts with the test strip to give a pink or red colour. indophenol oxidase test See OXIDASE TEST. indoxyl acetate (3-acetoxyindole) A reagent used in identification tests for e.g. species of Arcobacter and Campylobacter. Growth (from a non-selective medium) is suspended in distilled water, and a paper disc, impregnated with indoxyl acetate, is added; on incubation at room temperature for 20 minutes, a blue coloration indicates hydrolysis of indoxyl acetate. inducer exclusion (catabolite inhibition) The inhibition by glucose (or certain other readily metabolizable, ‘preferred’ substrates) of the uptake of certain substrates by bacteria; for example, if the bacteria are growing in a medium containing two substrates, one of the substrates is preferentially taken up and metabolized, and this substrate prevents the uptake of the other. There are several mechanisms for inducer exclusion; for exclusion of e.g. lactose in enterobacteria see CATABOLITE REPRESSION. Uptake of other (structurally unrelated) non-PTS sugars – e.g. maltose, melibiose – is inhibited in a similar way. In other cases, inducer exclusion may be due to competition between structurally related substrates for the same transport system or for shared components of the PTS; for example, in enterobacteria glucose can directly inhibit the uptake of galactose via a transport system common to both sugars. In certain Gram-positive bacteria (e.g. Streptococcus spp, Lactobacillus casei), accumulated sugar phosphates are actually expelled from the cell when e.g. glucose is added (inducer expulsion); this involves a two-step mechanism in which intracellular dephosphorylation of the sugar is followed by efflux of the free sugar. In these organisms regulation of sugar accumulation has been associated with the CcpA system (see CATABOLITE REPRESSION); phosphorylation of HPr at the Ser-46 site reduces its ability to be phosphorylated at the (routine) His-15 site by enzyme I, and this should reduce phosphate transfer to the PTS permeases and (hence) inhibit the uptake of sugars. inducer expulsion See INDUCER EXCLUSION. inducer protein Syn. activator: see OPERON. induction (1) (of enzymes, gene expression) See e.g. OPERON. (2) (of bacteriophage) See LYSOGENY. industrial alcohol (microbiological aspects) Large amounts of ethanol are produced commercially by the microbial fermentation of carbohydrates; ethanol is used primarily as a fuel (e.g. in GASOHOL), as a solvent, and as a feedstock in the chemical industry. ‘Fermentation ethanol’ (= ‘fuel ethanol’) may be produced by the ALCOHOLIC FERMENTATION of substrates such as MOLASSES and STARCH hydrolysates by strains of the yeast Saccharomyces; laboratory- and pilot-scale evaluations have been made of the economics of ethanol production from materials as diverse as cassava, Jerusalem artichoke, LIGNOCELLULOSE, sweet sorghum and WHEY – using various yeasts, certain bacteria, and mixtures of organisms. Since many organisms can utilize only mono- or disaccharides, polymers such as cellulose and starch must be subjected to acid or enzyme-catalysed hydrolysis before they can be fermented; strains of e.g. Clostridium thermocellum (which form 393

infectious bulbar paralysis infectious bulbar paralysis Syn. AUJESZKY’S DISEASE. infectious bursal disease virus (IBDV) A virus which causes severe inflammation of the BURSA OF FABRICIUS in chickens. IBDV closely resembles IPN VIRUS in morphology, genome etc. infectious centre See ONE-STEP GROWTH EXPERIMENT. infectious disease (communicable disease) Any disease which, under natural conditions, can be transmitted from one individual to another by a causal agent which passes either directly (by physical contact) or indirectly (e.g. by DROPLET INFECTION or via FOMITE or VECTOR) from the infected to the noninfected individual (i.e. HORIZONTAL TRANSMISSION); diseases passed on by VERTICAL TRANSMISSION include some which are normally ‘infectious’ (e.g. AIDS) as well as others (e.g. certain TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES) which are hereditary, i.e. not considered ‘infectious’. A transmissible disease may be transmitted from the affected individual to another individual, or to a fetus, by any means, including those processes that are involved in horizontal and vertical transmission as well as those involved in experimental infection (the latter form of transmission may or may not occur naturally in any given instance). TETANUS is an example of a non-infectious disease. (cf. CONTAGIOUS DISEASE; see also IATROGENIC.) [The transmission of infection (review): RMM (1995) 6 217–227.] infectious dropsy (of carp) (syn. rubella; infectious ascites; also: haemorrhagic septicaemia) An ‘umbrella term’ for at least two distinct FISH DISEASES affecting carp (Cyprinus spp): see SPRING VIRAEMIA OF CARP and CARP ERYTHRODERMATITIS; abdominal distension with generalized oedema are common to both diseases. infectious endocarditis See ENDOCARDITIS. infectious enterohepatitis Syn. BLACKHEAD. infectious equine arteritis virus Syn. equine arteritis virus: see ARTERIVIRUS. infectious foot-rot See FOOT-ROT. infectious haematopoietic necrosis (IHN) A FISH DISEASE characterized by massive destruction of the blood-forming tissues; the causal agent is a virus (see RHABDOVIRIDAE). infectious hepatitis Syn. HEPATITIS A. infectious jaundice See LEPTOSPIROSIS. infectious keratitis (infectious bovine keratoconjunctivitis; pinkeye) In cattle: KERATITIS or KERATOCONJUNCTIVITIS which occurs world-wide, particularly in young animals, usually in summer and autumn. The common causal agent is apparently Moraxella bovis. [Microbial flora of the bovine eye: VR (1986) 118 204–206.] (See also CATTLE DISEASES.) infectious mononucleosis (syn. glandular fever) An acute, selflimiting infectious disease of the lymphatic system which primarily affects children and young adults; it is caused by the EPSTEIN–BARR VIRUS (EBV). Transmission occurs by direct oral contact (‘kissing disease’) and may also occur by droplet infection. The incubation period is 1–7 weeks. In the typical ‘glandular fever’ syndrome (the anginose form), common in young adults, there is fever, pharyngitis (often with exudative tonsilitis) and swollen tender lymph nodes (with or without rash); jaundice and/or hepatosplenomegaly occur less commonly. Infrequently, the disease develops with fulminant hepatitis and VAHS (see HAEMOPHAGOCYTIC SYNDROME). Therapeutic approaches to the severe form of the disease may involve the use of agents such as ACYCLOVIR, CYCLOSPORIN A and corticosteroids. Lab. diagnosis may include demonstration of (a) increased levels of heterophil antibodies (see PAUL–BUNNELL TEST); (b)

mononucleosis and lymphocytosis; (c) the presence of atypical lymphocytes (enlarged, with foamy, vacuolated cytoplasm). (The atypical lymphocytes are not virus-infected B cells; they are T cells expressing the CD3 molecule.) [Haematology and cell-mediated immunity in infectious mononucleosis: BCH (1995) 8 165–199 (170–175).] (See also XLP SYNDROME; cf. CYTOMEGALIC INCLUSION DISEASE and EHRLICHIA.) infectious necrotic hepatitis (vet.) Syn. BLACK DISEASE. infectious nucleic acid (virol.) A nucleic acid which, when extracted from virions, can infect a host cell and give rise to progeny virions. Such a nucleic acid must be capable of being expressed and replicated in the cell in the absence of virion enzymes. Examples include DNA genomes which can gain access to the cell nucleus and which can be recognized and transcribed by host enzymes, and positive-sense ssRNA genomes which can be recognized and translated by host proteinsynthesizing machinery. Negative-sense ssRNA genomes are not infectious since an RNA-dependent RNA polymerase (present in the virion) is necessary for the synthesis of positive-sense mRNA. An infectious nucleic acid (e.g. that from polioviruses) may be able to infect cells not normally susceptible to the intact virion since the nucleic acid does not depend on the presence of a specific cell-surface receptor to initiate the infection process. (See also TRANSFECTION.) infectious pancreatic necrosis (IPN) A FISH DISEASE affecting hatchery-reared salmonid fry during the onset and early stages of feeding. Pancreatic tissue degenerates and becomes necrotic; mortality is often high. The causal agent is the IPN VIRUS. infectious polyarthritis (of pigs) Syn. GLASSER’S DISEASE. infectious spread (of plasmids) See EPIDEMIC SPREAD. infectious stunting syndrome (of chickens) See STUNTING SYNDROME. infective endocarditis See ENDOCARDITIS. infectivity (1) (of pathogenic microorganisms) The ability of a pathogen to become established on or within the tissues of a host. (See also VIRULENCE.) (2) (of a disease) The ease with which an infectious disease may be contracted under given conditions. (3) (viral) See END-POINT DILUTION ASSAY. inflammation In man and other animals: an acute or chronic response to tissue damage or to the presence of an allergen, or certain types of microorganism, within the tissues; inflammation may be initiated and sustained by microbial components and/or products. Inflammation is a protective response which commonly enables the body to overcome infection and return to normal function. Acute inflammation is characterized by redness, swelling, warmth (in the affected region), pain and loss of function. This manifestation of the body’s innate response to infection involves a diverse range of intercellular and intracellular signalling events – illustrated in the following generalized account of inflammation triggered by a Gram-negative bacterial pathogen which has breached the epithelial barrier. For convenience only, events mediated by complement and those mediated by cytokines are considered below under separate headings; the events described are representative of a process which is much more complex and which is still not understood fully. Complement-mediated events in inflammation. Activation of COMPLEMENT by LIPOPOLYSACCHARIDES (LPS) gives rise to (among other products) the fragments C3a and C5a; these fragments are anaphylatoxins which elicit HISTAMINE from e.g. MAST CELLS; C5a also acts as a chemotactic factor which attracts MONOCYTES and NEUTROPHILS to the infected site. 394

influenza virus C Histamine increases the permeability of small blood vessels, allowing efflux of plasma (hence the swelling) and exposing the pathogen to (i) increased amounts of antimicrobial agents (e.g. complement and antibodies) and (ii) cells of the immune system attracted by C5a. Histamine is also reported to stimulate the early expression of SELECTIN molecules (specifically P-selectins) on local vascular endothelium (apparently within minutes of stimulation). Cytokine-mediated events in inflammation. CYTOKINES (e.g. IL1, IL-8, TNF-a) are produced by local cells on stimulation by the pathogen. IL-1 and TNF-a promote the expression of E-selectins on local vascular endothelium. Leukocytes in local blood vessels bind weakly to endothelial selectins; binding involves certain carbohydrate ligands in the leukocyte membrane – e.g. sialyl-Lewis x (= CD15). This (labile) selectin–CD15 binding causes leukocytes to slow down and roll along the vascular endothelium in the direction of blood flow, bonds being continually made and broken; this is referred to as tethering. As well as CD15, the leukocyte cell membrane also contains adhesion molecules of the INTEGRIN family – although, in the absence of infection, these molecules are normally inactive; an example is the leukocyte functionassociated antigen 1 (LFA-1; CD11a/CD18). Chemokines, e.g. IL-8 (see above), promote the activation of LFA-1 (via phosphorylation), so that LFA-1 can then bind (strongly) to counterreceptors (e.g. ICAM-1, ICAM-2) on vascular endothelium. [Leukocyte rolling and firm adhesion (biophysical view): PNAS (2000) 97 11262–11267.] The captured leukocytes flatten, and then ‘crawl’ over the endothelium to a cell–cell junction – subsequently migrating between endothelial cells (a process called diapedesis or extravasation) into the affected area (apparently guided by the chemokine gradient). The mechanism of extravasation is not known, but platelet–endothelial cell adhesion molecule-1 (PECAM-1) appears to be required. As indicated, cytokines are important for the recruitment of immune cells to the local site of infection. (Neutrophils are commonly the dominant type of cell in the early stages of acute inflammation; macrophages often become prominent after ∼8 hours, and their ability to secrete FIBRONECTIN may be an important factor in tissue repair [wound healing (review): Science (1997) 276 75–81].) The importance of leukocyte recruitment to infected tissues is emphasized by those genetic disorders in which this process is inhibited (e.g. LEUKOCYTE ADHESION DEFICIENCY). Cytokines are also involved in the production of ACUTE-PHASE PROTEINS (q.v.). Antigen-stimulated T lymphocytes release g-interferon (IFNg) which activates MACROPHAGES. The pain associated with inflammation may be due e.g. to pressure on nerves and/or to PROSTACYCLIN. Chronic inflammation, which occurs e.g. in some persistent intracellular infections, is characterized by the formation of new connective tissue and by the presence of concentrations of macrophages; it often leads to the formation of a GRANULOMA. infliximab See TNF. influenza (flu; grippe) An acute, highly infectious human disease caused by influenza virus A (often widespread epidemics, occasionally pandemics) or influenza viruses B or C (typically sporadic outbreaks, often among children and young adults). (See INFLUENZAVIRUS for details of strains, including those in the 1997 bird flu in Hong Kong, the 1999 outbreak in Guangdong (China), and the 2004–2006 problem with strain H5N1; see also INFLUENZA VIRUS C, GASTRIC FLU and COMMON COLD.)

Infection generally occurs by inhalation of virus-containing aerosols, virions being deposited onto alveolar membrane or (larger droplets) onto mucous membrane lining the respiratory tract; in the latter case, virions may bind to sialic acid residues in mucoproteins (rather than to receptors on respiratory epithelium) – but such (abortive) binding can be broken by the viral neuraminidase. Incubation period: typically 1–3 days. Infection may be asymptomatic, or there may be a sudden onset with chills, fever, headache, muscular aches, anorexia, malaise etc.; fever subsides after 1–5 days, and respiratory symptoms (coryza, cough etc.) then become prominent. Recovery is usually rapid, although cough and malaise may persist for several weeks. Viral infection damages ciliated epithelium in the trachea and bronchi; loss of cilia predisposes to secondary bacterial infection and development of e.g. bronchial pneumonia involving organisms such as Streptococcus pneumoniae and/or Haemophilus influenzae. Secondary infections are particularly problematic e.g. in the elderly, debilitated and immunocompromised; apart from pneumonia, secondary infections may lead to complications such as tracheo-bronchitis, sinusitis, otitis media etc. (One early report indicated that, in mice, the severity of disease can be reduced by ozone [AEM (1982) 44 723–731].) Chemotherapy. Drugs such as AMANTADINE and rimantadine may afford some protection against influenza virus type A if administered before or soon after infection. (See also ZANAMIVIR.) Vaccines. The original, formalin-inactivated, whole-virus vaccines produce local and systemic side-effects. Split-product (split-virus) vaccines, containing H and N components of the virus (as opposed to entire virions), are tolerated better. Various alternative approaches to vaccines have been tried. For example, attempts have been made to prepare attenuated ‘live’ vaccines by using REASSORTANT VIRUSes containing e.g. surface glycoproteins from a currently epidemic strain and internal components from an attenuated strain. In some cases the attenuated strain was a temperature-sensitive (cold-adapted) virus, while in other cases it was a strain from another species with low virulence for man [e.g. avian strains: Book ref. 86, pp 395–405]. Vaccines have been prepared from synthetic oligopeptides that mimic glycoprotein epitopes [oligopeptide vaccines: MS (1984) 1 55–58] and with virosomes [Lancet (1994) 344 160–163]. Owing to the effects of antigenic variation, the components of influenza vaccines must be regularly reviewed to ensure that, when used, a given vaccine will generate protection relevant to the existing strain(s) of virus. [Efficacy of influenza vaccines: RMM (1996) 7 23–30.] influenza virus A See INFLUENZAVIRUS. influenza virus B See INFLUENZAVIRUS. influenza virus C A virus of the ORTHOMYXOVIRIDAE. It is physicochemically and morphologically similar to members of the genus INFLUENZAVIRUS, but differs in containing only 7 RNA segments (total MWt ca. 4–5 × 106 ) and in having only one type of surface glycoprotein (HA) which has both haemagglutinating and receptor-destroying activities, but apparently no neuraminidase activity. It has been shown that, contrary to previous assumptions, sialic acid may nevertheless be an essential component of the host cell-surface receptor [Virol. (1985) 141 144–147]. Influenza virus C primarily infects man, although it has been isolated from pigs in China; it generally causes only mild or subclinical disease of the upper respiratory tract. Antigenic drifting occurs slowly, but antigenic shift has not been observed (cf. INFLUENZAVIRUS). 395

Influenzavirus are apparently resistant to drying at room temperature, and survive at low temperatures in water. The virions can be preserved for long periods at −70° C. Infection of host cells; replication. The virion binds, via the HA protein, to specific cell surface receptors containing sialic acid residues; it is then internalized in a vesicle (endocytosis). Low pH within the vesicle promotes cleavage of the HA protein (by a host protease), and this leads to fusion of the viral envelope with the vesicle’s membrane; as a result, viral ribonucleoprotein and transcriptase are released into the cytoplasm of the host cell. (See also ENVELOPE.) The infectivity of a virion is abolished if antibodies have bound to the globular HA1 portion of the HA glycoprotein. Transcription of the (negative-sense) viral RNA occurs in the nucleus; it involves viral transcriptase but depends on the priming activity of the host’s (a-AMANITIN-sensitive) RNA polymerase II. (See also RIBAVIRIN.) Transcription gives rise to ten molecules of mRNA (two from each of genome segments 7 and 8 – each of which have two reading frames). Viral mRNAs are polyadenylated in the nucleus. Replication of the viral genome also occurs in the nucleus and involves viral transcriptase and the host’s RNA polymerase II. The progeny ribonucleoprotein structures are assembled in the nucleus, but details of the mode of assembly are not available. HA and NA proteins are synthesized on rough endoplasmic reticulum and subsequently migrate to localized sites in the plasma membrane. The type B influenzaviruses (but apparently not type A viruses) encode another glycoprotein, NB, whose reading frame overlaps that of NA; NB does not occur in the virion. Other non-structural (NS) proteins are produced in cells infected with A- or B-type viruses; their role(s) are unknown. Maturation of the virion occurs by budding through the cell membrane at sites containing HA and NA. Classification/nomenclature of influenzaviruses. Influenzaviruses are classified as subtypes on the basis of their HA antigens (15 different subtypes) and NA antigens (9 different subtypes). A given strain of virus is designated by a formula which indicates the following data: (i) type (i.e. A, B or C); (ii) the animal from which the strain was first isolated (omitted if the host was human); (iii) the place where the strain was first isolated; (iv) the strain number; (v) the year of isolation; and (vi) the particular HA (= H) and NA (= N) antigens. Example:

Influenzavirus A genus of viruses (family ORTHOMYXOVIRIDAE) which includes influenza virus type A and influenza virus type B; both viruses cause sporadic or epidemic INFLUENZA in man, but type A strains also cause epizootics in pigs, horses or birds (see e.g. FOWL PLAGUE and SWINE INFLUENZA) and (occasionally) pandemics in humans. (See also INFLUENZA VIRUS C.) Influenzaviruses are transmitted via aerosols or water, or by direct contact. Virions. The enveloped virions are pleomorphic, ca. 80–120 nm across; ‘filamentous’ forms of up to several micrometres in length are common. The genome consists of eight molecules of linear, negative-sense ssRNA (total MWt ca. 5 × 106 ); these RNA segments form a helical ribonucleoprotein complex with the (virus-encoded) NP protein. Associated with the RNA–NP complex are the viral proteins P1, P2 and P3 (also called PA, PB1 and PB2) which, together, constitute a transcriptase (i.e. an RNA-dependent RNA polymerase) which is required for synthesis of viral mRNA and for replication of the RNA genome. [Function of transcriptase (model): Book ref. 86, pp 73–84.] The ribonucleoprotein is surrounded by a layer of (virusencoded) matrix protein M1; this layer of M1 protein is wholly enclosed by the viral envelope. The viral M2 protein forms part of the envelope. It is encoded by genome segment 7 (as is M1); M2 (MWt ca. 13 × 103 ) is translated from a spliced transcript. The viral envelope (containing lipids derived from host cell membrane) forms the outermost layer of the virion. Two types of structure arise from the surface of the envelope. These structures are usually referred to as spikes and mushroomshaped projections (names which reflect their appearance under the electron microscope). Spikes. Each spike (∼10–15 nm long) consists of three identical glycoproteins. Because these glycoproteins can bind to red blood cells (and cause HAEMAGGLUTINATION) they are referred to as haemagglutinins (HA). However, the glycoproteins can bind to any type of cell which has a suitable sialic acid (= Nacetylneuraminic acid, NANA) receptor – e.g. cells of the respiratory epithelium. Each molecule of HA glycoprotein consists of two dissimilar polypeptide subunits which are linked by a disulphide bond; these subunits are termed HA1 (the larger subunit) and HA2. (The HA protein is encoded by segment 4 of the viral genome. It is synthesized as a single polypeptide chain which undergoes post-translational cleavage: an N-terminal signal sequence is removed, and the molecule is commonly cleaved to form HA1 (328 amino acid residues) and HA2 (221 amino acid residues) – which remain linked by a disulphide bond.) In each spike, the proximal HA molecule is attached to the envelope via a site in the HA2 subunit. Mushroom-shaped projections. Each individual mushroomshaped projection is a tetramer of another glycoprotein, NEURAMINIDASE (NA) (q.v.); each protein in the tetramer has a functional enzymic site. Propagation of influenzaviruses in vitro. The influenzaviruses can be propagated in embryonated hens’ eggs and e.g. in chick embryo cell cultures. Some authors prefer monkey kidney or human embryo kidney cells for primary isolation. (Eggs are used for vaccine virus production.) Inactivation of virions. Virions are rapidly inactivated by low pH (24 hours. (cf. CIRCADIAN RHYTHMS.) infrared radiation See dry-heat STERILIZATION. infrasubspecific rank Any rank below subspecies (see e.g. VARIETY). infundibulum (1) In some ciliates: the lower or inner (often tubular) region of the BUCCAL CAVITY; in peritrichs it corresponds to that part of the buccal cavity which excludes the PERISTOME (sense 1). (2) Any funnel-shaped structure. infusion agar Infusion broth (see NUTRIENT BROTH) gelled with 1.5–2.0% w/v AGAR. infusion broth See NUTRIENT BROTH. infusoria An archaic term for the various microscopic organisms – particularly ciliates – found in aqueous infusions of vegetable matter. INH Isonicotinic acid hydrazide: ISONIAZID. inhibitory medium See MEDIUM. initial(s) (microbiol.) Any part of a cell or organism which subsequently develops and/or differentiates to become a distinct and characteristic structure; the earliest or early stage(s) of a given structure. initial body See CHLAMYDIALES. initiation complex See PROMOTER. initiation mass See CELL CYCLE. initiator (of an operon) See OPERON. ink-cap fungi Species of COPRINUS whose autodigesting lamellae form a black, basidiospore-containing, ink-like liquid. Inkoo virus See BUNYAVIRUS. inlA gene See LISTERIOSIS. innate (mycol.) Refers to any fungal structure which is embedded in a substratum, or in the fungal thallus, such that its outer surface is more or less level with the surface of the substratum or thallus. inner primers See NESTED PCR. inner veil (mycol.) Syn. PARTIAL VEIL. inoculation (1) The placing of material (the INOCULUM) on or into a MEDIUM, TISSUE CULTURE, animal etc using an ASEPTIC TECHNIQUE. If the purpose of inoculation is to initiate a CULTURE, the inoculated medium must be incubated (see INCUBATION). (2) (immunol.) Syn. VACCINATION (1) or (2). inoculative infection (parasitol.) Infection in which a pathogen is introduced into the vertebrate host from the ANTERIOR STATION. (cf. CONTAMINATIVE INFECTION.) inoculum (1) Material used for the INOCULATION of a MEDIUM, TISSUE CULTURE, animal etc; it typically comprises or contains viable microorganisms. (2) (plant pathol.) Pathogenic microorganisms which have become established within a plant and which may give rise to disease. inoculum effect In the in vitro testing of bacteria for resistance to antibiotic(s): the phenomenon in which the MIC increases when the size of the test inoculum (cells/ml) is increased; for a given strain of bacteria the inoculum effect may differ greatly with different antibiotics. Inocybe See AGARICALES (Cortinariaceae). Inonotus A genus of fungi of the APHYLLOPHORALES (family Hymenochaetaceae) which form basidiocarps in which the context is reddish-brown and fibrous. I. dryadeus (formerly Polyporus dryadeus) forms bracket-type basidiocarps (context: monomitic) with a pale grey (later darkening) upper surface and a porous underside; basidiospores: whitish, spheroidal, ca. 7 µm diameter. It is parasitic on various types of oak (Quercus). (See also BUTT ROT and POCKET ROT.)

The surface glycoproteins of influenzaviruses undergo ANTIby this means, the virus may avoid the host’s immune response and give rise to new outbreaks of influenza. New strains of virus are generally not inactivated by antibodies induced by a previous strain – i.e. antibody-based protection tends to be strain-specific. Variation in surface antigens may involve ANTIGENIC DRIFT or ANTIGENIC SHIFT. Antigenic drift involves relatively small changes in the surface antigens, and this is associated with the regular occurrence of epidemic influenza. Antigenic shift involves major (and abrupt) changes in the surface antigens, and it happens infrequently. It has been recorded only in type A influenzaviruses; this apparently reflects the fact that type A strains can infect animals as well as man, and that, in mixed infections (involving viruses from different species), segments of the genome may undergo reassortment – resulting in the formation of novel hybrid subtypes containing genome segments from different co-infecting parent virions. In recent times, human strains typically displayed H1, H2 or H3, and N1, N2 or N3 antigens. Many other types of H and N antigens occur in animal strains, suggesting scope for the formation of new pandemic strains by reassortment. Fortunately, influenzaviruses are generally highly species-specific – so that transfer across the species barrier is assumed to occur only rarely. Transfer occurred when American harbour seals were infected by an avian H7N7 virus in 1980 [Virology (1981) 113 712–724] and pigs were infected by avian strains [JV (1996) 70 8041–8046]. Transfer across the species barrier may occur in a two-step process; for example, transmission of the human H3N2 subtype to avian hosts can be achieved after reassortment in pigs. The 1997 outbreak of bird flu in Hong Kong, which caused six deaths, resulted from avian-to-human transmission of a fowl plague strain (H5N1). Subsequently, no deaths from this strain were reported following large-scale slaughter of poultry. In 1999, two children in Hong Kong were infected with influenza A subtype H9N2 (strains A/Hong Kong/1073/99; A/Hong Kong/1074/99); these strains closely resemble a strain isolated from quail in 1997 (A/quail/Hong Kong/G1/97). Also in 1999, H9N2 viruses were isolated from patients with influenzalike illness in Guangdong province (China). The H5N1 and (Hong Kong) H9N2 human isolates are similar in the six genes that encode internal components of the virion, suggesting that H9N2 arose from reassortment of H5N1. Avian strains with these six genes might have a tendency to infect humans and may therefore have the potential to give rise to a novel human pathogen. [Relationship between H9N2 and H5N1 human isolates: PNAS (2000) 97 9654–9658]. H5N1 caused over 50 human deaths in East Asia in 2004–2005. Isolates from humans and those from birds consisted of two distinct clades. In all isolates the genes were of avian influenzaviruses, indicating that they were not derived through reassortment with human strains. Human-to-human transmission was described. [Evolution of H5N1 avian influenza viruses in Asia: EID (2005) 11(10). Influenza (special issue): EID (2006) 12(1) (January).] informational suppressor See SUPPRESSOR MUTATION. informosome See MRNA (b). infraciliature (ciliate protozool.) The subpellicular system which includes the kinetosomes and all the various associated microfibrillar and microtubular structures (see e.g. KINETODESMA; POSTCILIARY MICROTUBULES; TRANSVERSE MICROTUBULES). GENIC VARIATION;

397

inoperculate RFI v strand at a specific site in the IG region; the free 3′ end is elongated as in other ssDNA phages (q.v.). Genome lengths of displaced v ssDNA are cleaved by gp2, and each is circularized to form v ss cccDNA. At first, new v strands are converted to RFs. However, a phage-coded SSB protein (gp5) gradually accumulates, eventually coating the newly formed v strands and blocking their conversion to RFs (stage III). Phage coat proteins (at least gp8 and gp3) are synthesized as soluble cytoplasmic precursors with a ‘signal peptide’ at the amino end (see SIGNAL HYPOTHESIS); these proteins become inserted asymmetrically into the cytoplasmic membrane, the signal peptides are removed, and the proteins are ‘anchored’ within the membrane [PNAS (1982) 79 5200–5204]. Phage assembly – which requires THIOREDOXIN [PNAS (1985) 82 29–33] – occurs (in f1) at zones of adhesion between the cytoplasmic and outer membranes, f1 gp1 possibly being involved in the formation of these adhesion zones [JB (1985) 163 1270–1274] (cf. ADHESION SITE); gp8 displaces gp5, and the mature virion is finally extruded through the host cell envelope. insect diseases Bacterial pathogens of insects include e.g. Bacillus spp (see e.g. AMERICAN FOULBROOD, DELTA-ENDOTOXIN, MILKY DISEASE), Melissococcus pluton (see EUROPEAN FOULBROOD), and species of RICKETTSIELLA, SERRATIA and SPIROPLASMA. (See also CECROPINS and SARCOTOXINS.) Fungal entomopathogens include species of e.g. Ascosphaera (see CHALK-BROOD); ASCHERSONIA; Aspergillus (see e.g. STONEBROOD); BEAUVERIA; Coelomomyces (see BLASTOCLADIALES); CORDYCEPS; CULICINOMYCES; ENTOMOPHTHORA, ERYNIA and other fungi of the ENTOMOPHTHORALES; FUSARIUM; HIRSUTELLA; METARHIZIUM; NOMURAEA; SEPTOBASIDIALES; TERMITARIA; VERTICILLIUM. Protozoal entomopathogens include e.g. species of MALPIGHAMOEBA, NOSEMA and THELOHANIA. (See also CRITHIDIA, HERPETOMONAS and LEPTOMONAS.) For viral entomopathogens see e.g. BACULOVIRIDAE; CYTOPLASMIC POLYHEDROSIS VIRUS GROUP; DENSOVIRUS; DROSOPHILA X VIRUS; ENTOMOPOXVIRINAE; FLACHERIE; HOUSEFLY VIRUS; NODAVIRIDAE; NUDAURELIA b VIRUS GROUP; PICORNAVIRIDAE; POLYDNAVIRIDAE; SIGMA VIRUS. (See also INVERTEBRATE DISEASES and BIOLOGICAL CONTROL.) insect iridescent viruses See CHLORIRIDOVIRUS and IRIDOVIRUS. insect–microbe associations See e.g. AMBROSIA FUNGI; DUTCH ELM DISEASE; FUNGUS GARDENS; FUNGUS GNATS; INSECT DISEASES; MYCETOCYTE; TERMITE–MICROBE ASSOCIATIONS; WOODWASP FUNGI. insecticidal crystal protein (ICP) See BIOLOGICAL CONTROL. insertion mutation (addition mutation) A type of MUTATION in which one or more nucleotides are inserted into the genome; if the number of nucleotides inserted is not divisible by 3, the mutation will be a FRAMESHIFT MUTATION. Insertion mutations commonly result from the insertion of a TRANSPOSABLE ELEMENT or prophage (see also BACTERIOPHAGE CONVERSION). (cf. DELETION MUTATION.) insertion sequence (IS element) A TRANSPOSABLE ELEMENT which contains no genetic information other than that necessary for its transposition. (cf. TRANSPOSON.) An IS element may transpose independently, when it may be detectable by the effect(s) of its insertion at a new site, or it may occur as a terminal part of a composite (class I) TRANSPOSON. An IS element is defined by its ends: an INVERTED REPEAT sequence of ca. 10–40 bp has been found to occur at both ends in every IS element so far analysed; these inverted repeats are apparently necessary for transposition and are probably the recognition sites for the

inoperculate Lacking an OPERCULUM. inorganic pyrophosphate See PYROPHOSPHATE. iNOS See NITRIC OXIDE. inosine See NUCLEOSIDE and Appendix V(a). inositol Hexahydroxycyclohexane. Theoretically there are nine stereoisomers; of these, meso-inositol (= myo-inositol), scyllitol, d-inositol and l-inositol occur naturally, and only meso-inositol is common. Meso-inositol occurs widely e.g. in the phospholipids of microorganisms; it is required, in small amounts, for the growth of a number of microorganisms – including many yeasts (see e.g. BREWING). Inositol is used as a substrate in biochemical characterization tests for bacteria; it is attacked e.g. by Klebsiella pneumoniae. (See also CYCLITOL ANTIBIOTICS.) Inoue–Melnick virus A virus which has been isolated from patients with chronic CNS disease (including MULTIPLE SCLEROSIS) [JCM (1985) 21 698–701]. Inoviridae A family of SSDNA PHAGES in which the virions are rod-shaped or filamentous, the capsid subunits being arranged helically around one piece of ss cccDNA; the virions are chloroform-sensitive. On entry into a host cell the ssDNA is converted into a double-stranded replicative form from which progeny ssDNA can be synthesized. Mature phages are extruded through the host cell envelope. The host remains viable but grows more slowly than an uninfected cell. There are two genera: INOVIRUS and PLECTROVIRUS. [Book ref. 23, pp. 78–79.] Inovirus (filamentous phages) A genus of non-lytic SSDNA PHAGES of the INOVIRIDAE. Hosts: enterobacteria (for e.g. phages fd, f1, M13, If1, If2, IKe, ZJ/2), Pseudomonas (phages Pf1, Pf2), Xanthomonas (phages Xf, Xf2, Cf), and Vibrio (phage v6); most or all inoviruses can infect only ‘male’ cells (i.e. those containing CONJUGATIVE PLASMIDS). Proposed type member: bacteriophage fd; f1 and M13 are very similar to fd. The inovirus virion is a flexible filament (760–1950 × 6 nm, according to phage) comprising ss cccDNA (MWt ca. 1.9–2.7 × 106 ), one major coat protein (gp8, B-protein), and minor coat proteins A (gp3), C (gp9) and D (gp6) at 5, 10 and 5 copies/virion, respectively. Proteins A and D occur at one end of the virion; C seems to occur at the opposite end. The A-protein (gp3) is necessary for adsorption; the roles of C and D are unknown. The DNA loop fits inside the capsid (internal diam. ca. 2 nm) such that the two adjacent (antiparallel) strands of the loop are wound around each other in a type of double helix (pitch ca. 2.7 nm) despite the lack of homology between them; the helix seems to be stabilized by the coat protein [JMB (1982) 157 321–330]. The following refers to fd, f1 and M13; other inoviruses seem to be generally similar. Phages fd, f1 and M13 adsorb specifically to the tips of F and F-like pili (cf. BACTERIOPHAGE IKE, BACTERIOPHAGE IF1, LEVIVIRIDAE). During penetration of the host (which may involve pilus retraction) the capsid proteins (at least gp3 and gp8) become localized asymmetrically in the cell membrane. At it penetrates the cell, the phage DNA becomes coated with host SSB protein, initiating stage I (see SSDNA PHAGES). A unique 508-nucleotide intergenic (IG) region between genes 2 and 4 may remain uncoated; this region binds host RNA POLYMERASE holoenzyme which may recognize the secondary or tertiary structure of DNA in the IG region (which can form several hairpin loops). The RNA polymerase synthesizes an RNA primer at a specific site (ori ) in the IG region. The complementary (c) strand, and hence RF, is completed as in other ssDNA phages (q.v.). RF is supercoiled by GYRASE to become RFI (see RF). The c strand of RFI functions as template for transcription of phage genes. An early product is an endonuclease (gp2) which initiates stage II by cleavage of the 398

intein integrative suppression The phenomenon in which the integration of a plasmid into a bacterial chromosome suppresses the effect of a chromosomal mutation which has inhibited the initiation of chromosome replication; replication of the joint plasmid–chromosome replicon is apparently initiated at a site within the plasmid. Thus, e.g., as a result of integrative suppression, a temperature-sensitive dnaA mutant of Escherichia coli can carry out limited chromosome replication at a non-permissive temperature. integrins A family of CELL ADHESION MOLECULES found on various types of cell and involved in many aspects of cell physiology; the molecule is a heterodimer of proteins consisting of an a subunit non-covalently linked to a b subunit – the particular combination of a subunit (many types) and b subunit (few types) determining the biological activity of each integrin. Integrins of the b1 subfamily are found e.g. on various types of epithelial cell – either on the basolateral surface or (e.g. a6 b1 ) on the basal surface (i.e. adjacent to the basement membrane) [integrins (review): HJ (1993) 25 469–477]. These integrins have a major role in cell–cell and cell–matrix interaction – binding to ligands that include collagen, fibronectin and laminin; however, such interaction involves more than cell position and maintenance of tissue structure: integrin–ligand binding can also trigger signals that modulate a wide range of cell functions, including aspects of the cell cycle. The b1 integrins are also implicated as receptors for the adhesins of invasive pathogenic bacteria; for example, adhesins of Yersinia enterocolitica have been found to bind (in vitro) to the a5 b1 integrin of epithelial cells. The b2 integrins are found primarily on leukocytes; their expression on a given cell is apparently dependent on activation – e.g. cytokine-stimulated cells may exhibit the leukocyte function-associated antigen-1 (LFA-1; = CD11a/CD18; = aL b2 ) and the Mac-1 integrin (= CD11b/CD18; = aM b2 ); both of these integrins can bind to ICAM ligands (see IMMUNOGLOBULIN SUPERFAMILY and INFLAMMATION). The b2 integrins can also serve as receptors for bacterial adhesins. Thus, many integrins bind (via their a subunit) to ligands that contain the amino acid sequence Arg-GlyAsp (RGD), and this sequence is mimicked by the adhesin filamentous haemagglutinin (FHA) of Bordetella pertussis; the binding between FHA (RGD sequence) and Mac-1 (aM b2 ) of an activated macrophage assists bacterial invasion of the phagocyte. The b3 integrin aIIb b3 (gpIIbIIIa; = CD41b/CD61) is found on platelets and megakaryocytes; its ligands include fibrinogen, VON WILLEBRAND FACTOR and fibronectin. Failure to synthesize adequate amounts of this integrin results in deficient platelet aggregation (Glanzmann’s thrombasthenia). (See also LEUKOCYTE ADHESION DEFICIENCY.) [Defects in human integrins: Lancet (1999) 353 341–343.] integron A region of DNA which includes (i) a gene encoding a site-specific recombinase (see SITE-SPECIFIC RECOMBINATION) and (ii) a corresponding site for recombination into which one or more genes may be inserted [see e.g. JAC (1999) 43 1–4]. Integrons may have a role as a general gene-capture mechanism in bacterial evolution [PNAS (2001) 98 652–657]. intein In certain types of protein: an internal sequence of amino acids apparently capable of catalysing a self-splicing reaction in which the intein is excised (forming a separate protein) and the terminal parts of the original polypeptide (the two exteins) are joined to form a functional protein. [Review: TIBS (1995) 20 351–356. Intein sequences (review): NAR (1997) 25 1087–1093.]

corresponding transposition enzymes. Most IS elements also have the potential for encoding 1–3 polypeptides, presumed to include TRANSPOSASE component(s). In many IS elements a small open reading frame occurs within the larger open reading frame but in the opposite orientation; IS50 has overlapping genes (see Tn5 ). IS elements (designated IS1, IS2 etc) may be classified according to their terminal inverted repeats and the number of base pairs duplicated at the target site on insertion. Different IS elements transpose with different frequencies depending e.g. on the structure of the donor and target sequences, on the physiological state of the host cell, etc; frequencies of transposition range from ca. 10−9 to 10−5 per IS element per cell division. (See also e.g. IS1, IS5, IS101.) [Review: Book ref. 20, pp. 159–221.] insertion vector A CLONING vector which has a single site at which a sequence of exogenous DNA can be inserted (cf. REPLACEMENT VECTOR). inside-to-outside model A model which describes the mode of incorporation of PEPTIDOGLYCAN into the CELL WALL of a growing Gram-positive bacillus [FEMS Reviews (1986) 32 247–254; J. Theor. Biol. (1985) 117 137–157]. Essentially, layers of newly formed peptidoglycan are laid down just external to the cytoplasmic membrane – a region in which they are subject to minimal hydrostatic stress; as growth continues, the layers move outwards towards the cell surface (being replaced by new layers) and accordingly bear an increasing proportion of the hydrostatic pressure. Finally, near the region of maximum stress, the peptidoglycan becomes increasingly susceptible to autolysins, the (older) layers of peptidoglycan commonly being shed in fragments. inspissation The process of thickening. In microbiology: a process in which certain heat-coagulable substances (e.g. serum, homogenized hens’ eggs) – or media containing such substances – are solidified by heating to ca. 85° C for ca. 1 hour. ¨ (See e.g. LOWENSTEIN–JENSEN MEDIUM.) instructive theories of antibody-formation Theories (now untenable) which hold that the ability to produce specific antibodies develops in antibody-producing cells only after their initial exposure to the antigen, i.e., it is assumed that pre-existing specificity does not occur. In such theories antigen is supposed to act as a template for the production of specific antibodies or for the formation of an antibody-specifying nucleic acid. (cf. CLONAL SELECTION THEORY.) int (1) See e.g. BACTERIOPHAGE LAMBDA and BACTERIOPHAGE P22. (2) See MOUSE MAMMARY TUMOUR VIRUS. integral membrane protein See CYTOPLASMIC MEMBRANE. integrase See e.g. BACTERIOPHAGE l. integrase-type recombinase See SITE-SPECIFIC RECOMBINATION. integration host factor (IHF) In e.g. Escherichia coli: a heterodimeric protein consisting of polypeptide chains of apparent MWt 11000 and 9500 [JBC (1981) 256 9246–9253]; IHF, which has the ability to induce bends in DNA, has been associated with various roles that include e.g. stimulating the transcription of nitrogen-fixing operons [Cell (1990) 63 11–22], promoting expression of the tra operon in the F plasmid [JB (1990) 172 4603–4609], stimulating helicase-catalysed nicking of the F plasmid at oriT [JBC (1995) 270 28374–28380] and promoting gene specificity for a given sigma factor [EMBO (2000) 19 3028–3037]. IHF is also one of the factors needed for the on–off switching of type I fimbriae in Escherichia coli. (See also SIDD.) 399

interallelic complementation interallelic complementation See COMPLEMENTATION TEST. intercalary Not apical or terminal: e.g. formed or situated between apex and base of a given structure or between two cells in a chain of cells. intercalating agent Any dye possessing a planar chromophore which can insert (intercalate) between adjacent base pairs in dsDNA or in base-paired regions in ssDNA (e.g. HAIRPIN loops); bifunctional (bis) intercalating agents have two such chromophores per molecule (see e.g. QUINOXALINE ANTIBIOTICS). Intercalation forces the base pairs apart and causes (a) local unwinding of the helix, the degree of unwinding (unwinding angle, f) depending on the nature of the dye, and (b) an increase in the length of the DNA. In linear dsDNA these effects lead to an increase in viscosity and a decrease in sedimentation coefficient (s) of the DNA in proportion to the amount of dye intercalated. Intercalative binding is limited to a maximum of one dye molecule per 2–3 bp; the binding of a dye molecule at one site precludes binding of others at the adjacent sites (the neighbour exclusion principle). In circular dsDNA intercalation causes a local increase in pitch and thus a decrease in local (and hence average overall) twist. It follows from W r = Lk − T w (see DNA) that, as increasing amounts of dye intercalate in a negatively supercoiled molecule, the amount of writhe progressively decreases to zero (molecule behaves as relaxed), and then increases again as the molecule becomes positively supercoiled. The changes in writhe are accompanied by changes in viscosity of the DNA solution (increase to a maximum, then decrease) and in sedimentation coefficient of the DNA (decrease, then increase). Since intercalation relieves the strain of negative supercoiling, a negatively supercoiled cccDNA molecule has a higher affinity for intercalating agents than does the equivalent nicked or linear DNA, while a relaxed or positively supercoiled cccDNA has a lower affinity than the equivalent nicked or linear DNA. However, a cccDNA molecule has a limited capacity to unwind, and can therefore bind fewer molecules of intercalating agent than can equivalent linear or nicked circular DNA molecules (see e.g. ETHIDIUM BROMIDE). Many intercalating agents have antimicrobial and antitumour activity, inhibiting e.g. transcription, DNA replication etc, and inducing FRAMESHIFT MUTATIONS. In vivo, intercalation is often followed by DNA strand breakage, possibly due to the action of nucleases which recognize distortion of the helix at the intercalation sites. At lower concentrations some intercalators (e.g. aminoACRIDINES, ETHIDIUM BROMIDE) can cause the selective loss of small cccDNAs such as plasmids (see CURING (2)), mtDNA (see PETITE MUTANT), ctDNA, and kinetoplast DNA. (See also ACTINOMYCIN D; ANTHRACYCLINE ANTIBIOTICS; QUINOXALINE ANTIBIOTICS; TILORONE. cf. MITOMYCIN C and PSORALENS.) [Review of DNA-binding drugs: Bioch. J. (1987) 243 1–13.] intercistronic complementation See COMPLEMENTATION TEST. intercrines Syn. CHEMOKINES; thus, a-intercrines = a-chemokines, b-intercrines = b-chemokines. interesterification An industrial process in which fatty acyl residues are interchanged among the various triglycerides in a mixture of lipids; the process, which is catalysed e.g. by sodium methoxide, is carried out in order to modify the composition (and hence properties) of oils and fats. Interesterification can be carried out using certain microbial LIPASES for the production of useful mixtures of triglycerides which cannot be made by conventional chemical processes. [Enzyme-catalysed modification of oils and fats: PTRSLB (1985) 310 227–233.] interference (1) (virol.) The phenomenon in which the replication of one virus (the challenge virus) is partially or completely

inhibited by the presence in the host cells of another (interfering) virus. In homologous interference the challenge and interfering viruses are of similar or identical types, while in heterologous interference they are unrelated (see e.g. RUBIVIRUS). Interference may result e.g. from competition between the viruses for components of the replication apparatus, etc. (See also DEFECTIVE INTERFERING PARTICLE.) (2) (genetics) The phenomenon in which the occurrence of one recombinational event affects the chances of another occurring between adjacent regions of the same molecules of nucleic acid. In chiasma interference (= positive interference) the occurrence of a cross-over tends to prevent the occurrence of a second cross-over between nearby regions in the same duplexes; this effect decreases with increasing distance from the cross-over. In markers which are closely linked, a localized negative interference is sometimes observed: the occurrence of one recombinational event promotes recombination in an adjacent region; this can be due to the correction of adjacent sequences in hybrid DNA during gene conversion (co-conversion – see RECOMBINATION). interference-contrast microscopy See MICROSCOPY (d). interfering virus See INTERFERENCE (1). interferons (IFNs) A category of CYTOKINES which are able to inhibit the replication of many types of virus in (i) the IFNproducing cell, and (ii) cells exposed to exogenous IFNs; IFNs also have other important roles in host defence mechanisms (see later). Human interferons are divided into two main groups that are designated types I and II. The type I interferons (stable at pH 2) include IFN-a (∼17–26 kDa), IFN-b (∼21 kDa) and IFN-!; these interferons appear to be related – their genes (all of which are intron-less) may have developed from a common ancestral gene. The IFN-a gene exists in many allelic forms (subtypes). The type II (acid-labile) interferon IFN-g (∼25 kDa) exhibits little homology with type I interferons in terms of amino acid sequence; even so, the three-dimensional structure of the molecule has features in common with IFN-b. The gene encoding IFN-g contains three introns. Distinct types of interferon are found in other animals; for example, IFN-t (structurally related to IFN-!) occurs in cows and sheep. These animals also form e.g. interferons related to IFN-b. (A given type of interferon from one species may or may not be active in another species.) Human interferons of both types have antiviral activity, although this function appears to be of major importance primarily in type I interferons. The type II interferon (IFN-g) plays a major role in various immune defence mechanisms. Alpha interferon (IFN-a). IFN-a is produced by leukocytes. At least 14 subtypes of IFN-a occur in humans; these are designated IFN-a1, IFN-a2 etc. Beta interferon (IFN-b). IFN-b is produced by fibroblasts. Compared with IFN-a, the amino acid sequence of IFN-b exhibits only 30% homology; the two IFNs are antigenically distinct. Both IFN-a and IFN-b can induce intracellular antiviral effects that include degradation of viral RNA and inhibition of protein synthesis (described later). These IFNs also upregulate MHC class I molecules at the surface of virus-infected cells; this is of value in that class I molecules act as binding sites for CD8+ cytotoxic T cells (which kill virus-infected cells). Gamma interferon (IFN-g). IFN-g is produced by antigenically and/or mitogenically stimulated T lymphocytes. (See also 400

interleukin-1 INTERLEUKIN-18.) The active form of IFN-g is a non-covalentlybound dimer. Like type I interferons, IFN-g can upregulate class I MHC molecules. It can also upregulate class II MHC molecules on certain types of cell (including fibroblasts and endothelial cells); class II molecules promote the ability of cells to present antigen to CD4+ T cells (for which MHC class II molecules are binding sites). IFN-g is categorized as a pro-inflammatory cytokine (see CYTOKINES). In addition to its ability to upregulate MHC molecules, IFN-g can also e.g. (i) activate macrophages, (ii) stimulate the synthesis of NITRIC OXIDE, and (iii) promote class switching in B cells – upregulating e.g. IgG1 (and murine IgG2a) antibodies. Induction of interferons. Agents which induce the synthesis of interferons include many types of virus, certain bacteria and protozoa, mitogens, lipopolysaccharides, and double-stranded nucleic acids (e.g. poly(I:C) – a polymer consisting of one strand each of polyinosinic acid and polycytidylic acid). (See also TILORONE.) Many of the studies on induction of interferons have investigated transcriptional regulation of the gene encoding IFNb – apparently because this gene lacks the many subtypes of IFN-a and because, unlike IFN-g, it lacks introns. Induction of the gene encoding IFN-b during viral infection appears to involve activation of the transcription factor NF-kB; this seems to depend on phosphorylation of IkB by a dsRNA-dependent kinase designated PKR [PNAS (1994) 91 6288–6292]. (IkB normally inhibits NF-kB by binding to it; phosphorylation (and hence degradation) of IkB therefore results in the activation of NF-kB.) Viral infection also appears to promote synthesis of ‘interferon regulatory factor-1’ (IRF-1) which, together with activated NF-kB, may promote transcription from the regulatory region of the IFN-b gene. Antiviral activity of interferons. Exogenous interferons initially bind to specific cell-surface receptors. There are various kinds of receptor for type I interferons; some (not all) are common to IFN-a, IFN-b and IFN-!. The receptor for IFN-g is distinct from those that bind type I interferons. In all cases, however, the receptor for an interferon consists of a heterodimeric structure associated with tyrosine kinases on the cytoplasmic side; the kinases are involved in initiating the intracellular signal that leads to transcriptional upregulation of certain genes. A generalized account of antiviral activity is as follows. The binding of interferon to a specific receptor activates a JAK–STAT signalling pathway (see JAK and STATs in CYTOKINES); this promotes transcription of certain genes encoding antiviral proteins. The type of interferon-inducible protein produced in any given case will depend on the type of cell and the type of interferon. Proteins induced by interferons include e.g. receptors for TNF; class I and II MHC antigens; nitric oxide synthetase; CD54 (inducible only by IFN-g); Mx protein (an inhibitor of influenzavirus replication inducible only by type I interferons); PKR (a protein kinase); and 2–5A synthetase. The two latter proteins are involved in generalized antiviral activity, as follows. When activated by dsRNA, the PKR kinase phosphorylates (and therefore inactivates) the a subunit of the protein synthesis initiation factor 2; this inhibits formation of initiation complexes and, hence, inhibits the synthesis of both viral and cellular proteins. The 2–5A synthetase (activated by dsRNA) catalyses the synthesis of 2–5A (= 2,5-oligoadenylate). The 2–5A activates

an enzyme, RNase L (also called RNase F), which can cleave viral and cellular RNA; however, 2–5A is unstable, being enzymically degraded by 2′ ,5′ -phosphodiesterase. The antiviral activity of interferons has been assayed in vitro by a plaque-reduction method in which cultured cells are treated with IFN and subsequently challenged with virus; the titre of IFN may be taken as the reciprocal of the highest dilution of IFN that produces a 50% decrease in the number of plaques. Therapeutic uses of interferons. Both natural and recombinant forms of interferon (types I and II) have been evaluated for clinical use in a range of diseases, including various types of malignancy, Kaposi’s sarcoma (IFN-a), multiple sclerosis (IFN-b), diseases of viral aetiology, and disease caused by Mycobacterium tuberculosis (IFN-g). Commercial products include Alferon N (multicomponent IFN-a; Interferon Sciences, USA); Betaferon and Betaseron (recombinant IFN-b; Schering AG); Gammaferon (recombinant IFN-g; Rentschler, Germany). [Clinical uses of interferons: Book ref. 226, pp 237–271.] The enhanced capacity of lymphocytes to secrete IFN-g when thalidomide is used for adjuvant therapy may offer an explanation for the ability of thalidomide to bring about clinical improvement in patients infected with e.g. Mycobacterium tuberculosis and HIV [AAC (2000) 44 2286–2290]. (See also ELISPOT ASSAY (for TB).) intergenic complementation See COMPLEMENTATION TEST. intergenic repeat unit Syn. ERIC SEQUENCE. intergenic spacer region See RIBOTYPING. intergenic suppression See SUPPRESSOR MUTATION. intergenote A partial zygote formed by heterologous TRANSFORMATION (i.e., transformation in which the donor DNA is derived from a species different from that of the recipient). intergranal frets See CHLOROPLAST. interkinesis See MEIOSIS. interkinetal Refers e.g. to the plane of cell division typical of members of the OPALINATA: longitudinal, between the rows of kineties. (cf. HOMOTHETOGENIC.) interleukin-1 (IL-1) A cytokine (see INTERLEUKINS) secreted by various types of cell, including monocytes, fibroblasts, dendritic cells and endothelial cells. There are several forms of IL-1: IL1a (previously called lymphocyte activating factor, LAF) and IL-1b (both pro-inflammatory cytokines with similar or identical functions) and IL-1ra; IL-1ra binds to the cognate receptor of IL-1a and IL-1b but, having no agonist activity, it functions as an antagonist of the a and b forms of IL-1. (There are two types of receptor for IL-1 but only one is functional; the other (‘decoy’) receptor does not initiate intracellular signals when IL-1a or IL-1b binds to it.) For IL-1g see INTERLEUKIN-18. The mature forms of IL-1a and IL-1b are produced by intracellular cleavage of precursor pro-proteins. IL-1b is cleaved (activated) by a cysteine protease referred to as IL-1b-converting enzyme (ICE). (ICE also has a role in APOPTOSIS.) Cells stimulated to produce IL-1 generally form both the a and b types; however, in at least some cases (e.g. a monocyte responding to LPS), the amount of IL-b produced is much greater than that of IL-1a. The known or presumed functions of IL-1a and IL-1b in vivo include: Activation, and induction of cytokine synthesis in macrophages. Induction of ACUTE-PHASE PROTEINS in the liver. Stimulation of activated B cells to proliferate and form antibody (and possibly stimulation of T cells). 401

interleukin-2 Induction of synthesis of endothelial adhesion molecules during INFLAMMATION; induction of e.g. IL-1 and colony-stimulating factors in endothelial cells. Induction of fever (apparently by stimulation of prostaglandins in the temperature regulatory region of the brain). The biological activities of IL-1 overlap with those of tumour necrosis factor (TNF); IL-1b and TNF-a have been found to be synergistic when jointly administered to animals. Moreover, IL1b and TNF-a stimulate the production of each other (as well as their own synthesis). However, despite the overlap in activities, it appears that, unlike TNF-a, IL-1 cannot promote cytotoxic activity via apoptosis. interleukin-2 (IL-2; killer helper factor, KHF; T cell growth factor, TCGF) A cytokine (see INTERLEUKINS) produced by T lymphocytes. In vitro, IL-2 can stimulate proliferation of antigenically or mitogenically activated T cells; in vivo, it appears to promote the growth/differentiation of T cells and to enhance the cytotoxicity of CD8+ T cells and NK cells. (See also CD28 and ANTIBODY FORMATION.) IL-2 promotes development of the Th1 subset of T lymphocytes, and is one of the cytokines secreted by these proinflammatory cells. The gene encoding IL-2 (like that encoding IFN-g) contains three introns. (See also SEVERE COMBINED IMMUNODEFICIENCY.) interleukin-4 (IL-4) A cytokine (see INTERLEUKINS) produced by lymphocytes of the Th2 subset. IL-4 promotes differentiation of Th0 to Th2 cells, and in antigenically stimulated B cells it seems to e.g. induce class switching to IgG4 and IgE (IgG1 and IgE in mice). IL-4 is also involved in the formation of eosinophils – probably through its ability to promote the Th2 subset and (consequent) secretion of interleukin-5 (a cytokine required for the normal development of eosinophils). The ability of naive CD4+ T cells to secrete IL-4 is inhibited when ICAM-1 is co-expressed with antigen on the antigenpresenting cell [PNAS (1999) 96 3023–3028]. interleukin-5 (IL-5) A cytokine (see INTERLEUKINS) produced by the Th2 subset of T lymphocytes (see also INTERLEUKIN-4). IL5 appears to be the main stimulus for eosinophilia in certain parasitic infections. [Eosinophilia and helminthic infections: BCH (2000) 13 301–317.] interleukin-6 (IL-6) A cytokine (see INTERLEUKINS) produced by a variety of cells, including monocytes/macrophages, fibroblasts, endothelial cells and the Th2 subset of T lymphocytes. Synthesis of IL-6 in monocytes/macrophages can be induced by LPS (lipopolysaccharides) or by cytokines (TNF-a or IL-1); the P FIMBRIAE of uropathogenic Escherichia coli are reported to be potent inducers of IL-6. IL-6 appears to have many roles in vivo. These roles include stimulation of growth, differentiation and antibody production in B cells, and induction of ACUTE-PHASE PROTEINS; in at least some cases IL-6 may contribute to the development of fever. interleukin-8 (IL-8) A cytokine (see INTERLEUKINS) produced by many types of cell, including monocytes/macrophages, neutrophils, fibroblasts, epithelial and endothelial cells, keratinocytes, NK cells and T cells. Agents that stimulate production of IL-8 include LPS and the cytokines IL-1 and TNF; production of IL-8 is inhibited by certain cytokines (e.g. IFN-g and IL-4) and by glucocorticoids. IL-8 acts as a chemoattractant and activator primarily for neutrophils (see CHEMOKINES), and its main role in vivo is believed to be the recruitment of leukocytes to sites of infection/INFLAMMATION. IL-8 is found in many inflammatory diseases

but, unlike e.g. TNF, it does not induce shock when administered experimentally. interleukin-10 (IL-10) A cytokine (see INTERLEUKINS) produced e.g. by the Th2 subset of T cells and by monocytes stimulated by LPS. IL-10 has anti-inflammatory activity; for example, it inhibits proliferation and release of cytokines in antigenstimulated Th1 cells, it inhibits release of pro-inflammatory cytokines from monocytes and macrophages, and it promotes proliferation and synthesis of antibodies in activated B cells. interleukin-12 (IL-12; natural killer stimulatory factor) A cytokine (see INTERLEUKINS) produced by B cells and also by macrophages acting as antigen-presenting cells. IL-12 appears to be essential for development of the Th1 subset of T cells from naive T cells; it also stimulates cytotoxicity in NK cells and enhances the release of cytokines from NK cells, macrophages and T cells. IL-12 also has anti-angiogenic activity (it inhibits development of new blood vessels). The ability of macrophages to synthesize IL-12 is inhibited by the binding of measles virus to the complement receptor CD46. interleukin-18 (syn. interleukin-1g) An INTERLEUKIN produced e.g. by macrophages, keratinocytes and (murine) Kupffer cells. IL-18 is a pro-inflammatory cytokine which induces IFN-g in T cells (and murine spleen cells), enhances cytotoxicity in NK cells, and promotes the Th1 (rather than Th2) immune response. IL-18 also triggers activation of NF-kB and synthesis of e.g. IL-1b, TNF-a and Fas ligand. IL-18 is synthesized in a biologically inactive form; it is activated by IL-1b converting enzyme (ICE; also referred to as caspase-1). IL-18-mediated induction of IFN-g can be inhibited by the binding of poxvirus-encoded proteins to IL-18 [PNAS (1999) 96 11537–11542 (correction: PNAS (2000) 97 11673)]. interleukin-21 An INTERLEUKIN which, in vitro, influences the proliferation/maturation of NK cells from bone marrow, the proliferation of B cells co-stimulated with anti-CD40, and the proliferation of T cells co-stimulated with anti-CD3. IL-21 is synthesized by activated CD4+ T cells. [Nature (2000) 408 57–63.] interleukins Certain CYTOKINES which are secreted by, and effective on, leukocytes (white blood cells) – but which, in some cases, can also be secreted by other types of cell (e.g. endothelial cells). It should be noted that the nomenclature is inconsistent in that some cytokines which conform to this description (e.g. tumour necrosis factor) are not formally referred to as interleukins; moreover, some interleukins are also classified in other named categories (e.g. interleukin-8 is a chemokine). Each interleukin (IL) is designated by a number – e.g. IL-4, IL-6, IL-21. (See also separate entries for individual interleukins.) intermediate filaments (IFs; IMFs) In most types of eukaryotic cell: protein filaments, ca. 7–11 nm thick, which form part of the CYTOSKELETON. IMFs appear to be much more stable than either microfilaments or microtubules, and their roles are believed to include the strengthening of the cytoskeleton. IMFs differ e.g. according to cell type and species, and the monomers of different IMFs vary widely in size; the monomer vimentin (MWt ca. 55000) occurs in many types of cell. intermediate host In heteroxenous coccidia: the host in which the asexual phase occurs (see EIMERIORINA). internal guide sequence See SPLIT GENE (b). internalin A See LISTERIOSIS. interphase (1) See MITOSIS. (2) See DICTYOSTELIOMYCETES. interrupted gene Syn. SPLIT GENE. 402

invertase interrupted mating A technique used for studying gene transfer during bacterial CONJUGATION. For example, a population of cells of an Hfr strain of Escherichia coli is mixed with an F− (recipient) population (time zero). At regular intervals of time, a sample is taken from the mating mixture, agitated to separate mating cells, diluted to reduce the probability of further mating contacts, and plated on a medium which will support the growth of particular recombinant(s) but not of the parent Hfr or recipient cells. Samples taken within ca. 5 min of time zero generally do not contain recombinants; samples taken after increasing periods of time will contain recombinants with an increasing number of donor genes. Since donor genes are transferred sequentially, a given donor gene will appear in a recombinant after a characteristic time interval which depends on the distance of the gene from the origin of transfer and on the efficiency with which the gene recombines with the recipient’s chromosome. Thus, the time of transfer of a gene gives an indication of the position of that gene in the donor chromosome, and interrupted mating can be a useful means of genetic mapping. (In practice, the further a gene is from the origin of transfer, the less frequently will it be transferred owing to the increased chances of strand breakage during the longer conjugation times; thus, the yield of recombinants expressing a given donor gene is also indicative of the position of that gene.) In E. coli the time taken to transfer the entire chromosome is typically ca. 100 min at 37° C (estimated using several Hfr strains differing in the position of the origin of transfer). The position of any gene can be given in terms of the time (in minutes) of transfer of that gene relative to a given origin of transfer – arbitrarily standardized at the thr (threonine synthesis) locus (zero minutes). interspecies hydrogen transfer The mutually beneficial, unidirectional transfer of H2 from H2 -producing to H2 -utilizing organisms in a given ecosystem (see e.g. ANAEROBIC DIGESTION). interstitial pneumonia See PNEUMONIA. intervening sequence See SPLIT GENE. intestinal tract flora See GASTROINTESTINAL TRACT FLORA. intimin See EPEC and PATHOGENICITY ISLAND. intine See CYST (a). Intoshellina See ASTOMATIDA. intoxication Poisoning. See e.g. FOOD POISONING and MYCOTOXICOSIS. intra-epithelial lymphocytes (IELs) See T LYMPHOCYTE. intra vitam staining See VITAL STAINING. intracisternal A-type particles See A-TYPE PARTICLES. intracistronic complementation See COMPLEMENTATION TEST. intracytoplasmic membranes (also: cytomembranes) (bacteriol.) Membranous systems or structures present within the cytoplasm in certain bacteria; according to type, the membranes may or may not be continuous with the CYTOPLASMIC MEMBRANE. Intracytoplasmic membranes occur e.g. in members of the METHYLOCOCCACEAE and NITROBACTERACEAE, in HYDROCARBONutilizing bacteria, in photosynthetic bacteria (see CHLOROSOMES, CHROMATOPHORE (sense 2), THYLAKOIDS), etc. (See also MESOSOME and POLAR MEMBRANE.) intragenic complementation See COMPLEMENTATION TEST. intragenic suppression See SUPPRESSOR MUTATION. Intrapes See UREDINIOMYCETES. Intrasporangium A genus of aerobic bacteria (order ACTINOMYCETALES, wall type I). The organisms form branching substrate mycelium (hyphae: 0.4–1.2 µm in diam.) but no aerial hyphae; intercalary or subterminal swellings (‘sporangia’) occur in old cultures. Type species: I. calvum.

intravital staining See VITAL STAINING. intrinsic resistance (to antibiotics) See ANTIBIOTIC. intron See SPLIT GENE. intron homing (in bacteria) The process in which introns (of either group I or group II) spread, in replicative fashion, to allelic intron-less genes. The mechanism of intron homing differs in the two types of intron. Intron homing in group I introns is initiated when a DNA endonuclease (homing endonuclease), encoded within the intron sequence, acts at the potential insertion site in an intron-less allele, typically making a double-stranded cut. The lesion is repaired by enzymes which use the intron-containing gene as a template; in this way, a copy of the intron is synthesized in the insertion site of the intron-less allele. In group II introns, the process begins with an intron-encoded protein which forms a complex with an RNA copy of the intron. This RNA–protein (RNP) complex is able to recognize the insertion site in an intron-less allele. The RNP complex can then (i) cut both strands at the target site, covalently inserting the RNA into one strand, and (ii) form a cDNA copy of the RNA (by virtue of the protein’s reverse transcriptase function); the RNA is then replaced by DNA. The involvement of a reversetranscribed copy of the intron (cf. group I introns) is reflected in the term retrohoming for the process in bacterial group II introns. Intron homing (in both group I and II bacterial introns) is outlined in a recent minireview [JB (2000) 182 5281–5289 (5281–5282)]. inulin A linear FRUCTAN consisting of (2 → 1)-b-linked fructofuranose residues. Inulins occur e.g. as storage polysaccharides in certain plants (e.g. in dahlia tubers). inulinase An enzyme (b-fructosidase, 2,1-b-D-fructan-fructanohydrolase, EC 3.2.1.7) which hydrolyses INULIN to FRUCTOSE. Many microbial inulinases also show INVERTASE activity, and some can hydrolyse bacterial LEVAN. Microbial inulinases may prove useful in the commercial production of fructose from plant inulins [AAM (1983) 29 139–176]. inv gene (Yersinia) See FOOD POISONING (Yersinia). inv–spa genes See PATHOGENICITY ISLAND and FOOD POISONING (Salmonella). invasin In certain pathogenic bacteria: a type of cell-surface molecule which promotes uptake of the pathogen by (eukaryotic) host cells. Examples of invasins include ‘invasin’ (see FOOD POISONING (Yersinia)) and ‘internalin A’ (see LISTERIOSIS). In strains of UPEC (q.v.), the FimH adhesin appears to function as an invasin. invasion (of phagocytes by pathogens) See end of section (a) in PHAGOCYTOSIS. invasiveness (of a pathogenic microorganism) The ability of a pathogen to spread through a host’s tissues; the degree of invasiveness reflects the relative insusceptibility of the pathogen to the host’s defense mechanisms. (See also AGGRESSIN.) invasomes See FOOD POISONING (Salmonella). inversion (mol. biol.) See e.g. CHROMOSOME ABERRATION and RECOMBINATIONAL REGULATION. invert sugar See INVERTASE. invertase (1) (saccharase; sucrase; b-fructosidase; b-D-fructofuranoside fructohydrolase; EC 3.2.1.26) An enzyme which hydrolyses SUCROSE to glucose and fructose; it can also hydrolyse raffinose to fructose and melibiose. Invertase occurs in many yeasts and other fungi and in higher plants; it is obtained commercially mainly from BAKERS’ YEAST in which it occurs in the cell wall as a mannoprotein containing ca. 50% mannose. Invertase is used chiefly in the conversion of sucrose to ‘invert 403

invertebrate diseases sugar’ (a mixture of glucose and fructose) used as a sweetening agent. (See also ENZYMES.) (2) (mol. biol.) A recombinase responsible for the inversion of a segment of DNA: see RECOMBINATIONAL REGULATION. invertebrate diseases See e.g. CRUSTACEAN DISEASES; INSECT DISEASES; NEMATOPHAGOUS FUNGI; OYSTER DISEASES. inverted repeat (IR) In a double-stranded nucleic acid molecule: either of two regions in which the sequences of base pairs are similar or identical and have the same polarity but are opposite in orientation, e.g.:

molecular form (I2 ); however, an iodine solution was reported to inactivate poliovirus (at 25° C) more efficiently at pH 10 than at pH 6 (at pH 10 iodine occurs mainly as hypoiodous acid, HIO) [AEM (1982) 44 1064–1071]. Both I2 and HIO are strongly microbicidal; the ratio I2 :HIO in a solution of iodine is affected not only by pH but also by the total concentration of dissolved iodine and by the presence of organic matter [Book ref. 65, pp. 183–196]. The staining, corrosive and irritant properties of iodine can be overcome by complexing the element with certain high-MWt surface-active compounds – e.g. polyvinyl pyrrolidone, certain quaternary ammonium compounds; such complexes are referred to as iodophores (or iodophors). Iodophores have the antimicrobial properties of iodine together with the detergent properties of the surfactant, but only ca. 80% of the bound iodine is released; their response to pH is similar to that of iodine. Iodophores have been used e.g. for the disinfection of swimming-pool water and dairy equipment; polyvinyl pyrrolidone–iodine (povidone–iodine, PVP–iodine) has been used for treating skin and mucous membrane infections involving species of Streptococcus, Staphylococcus and Candida. Betadine and Wescodyne are iodophores used as antiseptics/disinfectants. (cf. IODOFORM; IODONIUM COMPOUNDS; see also CHLORINE.) (b) (as a stain) See e.g. LUGOL’S IODINE. iodinin A red, water-soluble pigment: 1,6-phenazinediol-5,10dioxide; crystals of iodinin are formed in the culture medium e.g. by Microbispora parva. iodochlorohydroxyquin See 8-HYDROXYQUINOLINE. 5-iodo-2′ -deoxyuridine Syn. IDOXURIDINE. iodoform (CHI3 ) A compound once widely used as an antiseptic; its antimicrobial activity is poor compared with that of IODINE. iodonium compounds Compounds of the form R2 IX, in which R is an organic group and X is an inorganic ion; such compounds (e.g. diphenyliodonium chloride) contain trivalent iodine, are strongly basic, and possess antimicrobial properties, but their activity against spores is doubtful. iodophores (iodophors) See IODINE (a). ion-exchange chromatography See CHROMATOGRAPHY. ion-motive force phosphorylation See ELECTRON TRANSPORT PHOSPHORYLATION. ion transport Ion fluxes across ENERGY-TRANSDUCING MEMBRANES are involved e.g. in certain types of energy conversion (see e.g. PROTON ATPASE, PROTON PPASE, END-PRODUCT EFFLUX), in the ion-linked uptake of certain substrates, in the regulation of intracellular osmotic pressure and pH, in the generation of electrochemical gradients of specific ions, and (apparently) in morphogenetic processes (see GROWTH (fungal)). Since ions cannot pass freely across such membranes (cf. OUTER MEMBRANE) their transmembrane translocation requires a driving force and more or less specific TRANSPORT SYSTEMS which may involve UNIPORT, ANTIPORT or SYMPORT processes. The energy needed for transmembrane ion translocation may be provided, directly, by (a) a concentration gradient of the ion itself; (b) a gradient of another ion – e.g. H+ (see pmf in CHEMIOSMOSIS) or Na+ (see SODIUM MOTIVE FORCE); (c) ATP hydrolysis (see e.g. PROTON ATPASE); (d) the direct coupling of metabolism to ion transport (see ELECTRON TRANSPORT CHAIN and SODIUM MOTIVE FORCE); or (e) light (see PHOTOSYNTHESIS and PURPLE MEMBRANE). Ion electrochemical gradients as driving forces in ion transport. A difference in the concentrations of a given ion on either side of a membrane constitutes an electrochemical gradient which may be able to provide a driving force for the transmembrane transfer of the ion itself or of other types of ion. However, the presence of such a gradient, and the existence of transmembrane route(s) for a given ion, does not necessarily mean that

5′ . . . GGCT . . . AGCC . . . 3′ 3′ . . . CCGA . . . TCGG . . . 5′ (The repeated sequences may or may not be contiguous.) In a single-stranded nucleic acid, IRs are sequences which are complementary and opposite in polarity, i.e., equivalent to one of the strands of a double-stranded IR. (cf. DIRECT REPEAT; see also HAIRPIN and PALINDROMIC SEQUENCE.) invertible DNA See RECOMBINATIONAL REGULATION. invJ gene (Salmonella typhimurium) See NEEDLE COMPLEX. involution forms (of bacteria) Morphologically or otherwise aberrant cells often seen in old cultures or among organisms cultured under harsh or hostile conditions (e.g. in the presence of sub-lethal concentrations of antibiotics). Involution forms are generally regarded as degenerate cells, degeneracy commonly being ascribed to the action of autolysins, failure of cell wall synthesis, or failure of cell division without cessation of macromolecule synthesis. (cf. L-FORM.) Iodamoeba A genus of protozoa of the AMOEBIDA. I. b¨utschlii occurs in the human intestine; it is non-pathogenic. Trophozoites (ca. 9–20 µm diam.) contain numerous vacuoles and form blunt pseudopodia slowly; the single nucleus lacks peripheral chromatin and contains a large karyosome which is variable in shape and location and which is surrounded by clusters of granules. Cysts are irregular in shape, ca. 5–16 µm in diam., containing (usually) a single nucleus and a large persistent glycogen granule which stains a characteristic dark-brown with iodine; chromatoid bodies are usually absent. iodinated density-gradient media Media used e.g. for the separation of macromolecules and sub-cellular fractions by isopycnic ultraCENTRIFUGATION. High-density, non-ionic media in this category include e.g. a tri-iodinated benzamido derivative of glucose (Metrizamide), and a tri-iodinated derivative of benzoic acid (substituted with three highly hydrophilic aliphatic side chains) having a MWt of 821 and a density of 2.1 g/ml (Nycodenz – trade mark of Nyegaard & Co., Oslo, Norway). iodine (a) (as an antimicrobial agent) Iodine has microbicidal activity against a wide range of bacteria (including endospores), fungi, and viruses; in many cases its antimicrobial activity appears to be due to the combination of molecular iodine with proteins (e.g. tyrosine is irreversibly iodinated). Iodine is readily soluble in organic solvents; tincture of iodine (used as an ANTISEPTIC) contains ca. 2.5% iodine in an ethanol–water solution of potassium iodide. The (low) solubility of iodine in water is increased by the presence of iodide, when the tri-iodide (I3 − ) is formed; I3 − itself is not antimicrobial, but it readily decomposes to release free iodine. For skin antisepsis aqueous solutions are generally preferred since they are less irritant than alcoholic solutions; the latter have been used e.g. for the disinfection of thermometers. The antimicrobial activity of aqueous iodine solutions is sometimes said to be maximal under acid conditions (pH 6 or below) – when dissolved iodine is present largely in the 404

ionizing radiation the ion will be translocated: ion transport is subject to various intracellular and extracellular regulatory factors; moreover, the transmembrane route taken by a given ion may vary according e.g. to the extracellular concentration of that ion. The potential energy of a transmembrane gradient of ions can be considered in terms of the change in Gibbs free energy which occurs when a charged species is transferred down an electrochemical gradient. Thus, e.g., if one mole of an ion, Xm+ , is transferred down an electrical potential gradient of 1y millivolts, from concentration [Xm+ ]′ to [Xm+ ]′′ , the net change in Gibbs free energy (1G) can be obtained from the general electrochemical equation: 1G = −mF1y + 2.3RT log10

[Xm+ ]′′ [Xm+ ]′

Ca2+ uptake are modified by the operation of Ca2+ efflux systems, and a steady-state level of intramitochondrial Ca2+ is maintained by the continual cycling of Ca2+ across the membrane. Modes of ion transport include: (a) Uniport driven by pmf. Examples include pmf-mediated ATP synthesis (see PROTON ATPASE) and the uptake of Ca2+ by mitochondria [Book ref. 126, pp. 251–255]. (b) Uniport coupled to ATP hydrolysis. One example is the so-called Kdp transport system for K+ uptake in Escherichia coli. In this system, ATP hydrolysis (rather than pmf) at a membrane-bound K+ -ATPase (‘K+ -dependent ATPase’, ‘K+ stimulated ATPase’, ‘K+ -pump’) brings about the transmembrane translocation of K+ into the cell against a concentration gradient; the Kdp system becomes derepressed under conditions of K+ starvation. [K+ pathway in E. coli : Book ref. 126, pp. 653–666.] Enterococcus faecalis has been reported to use an Na+ -ATPase for Na+ extrusion [JB (1984) 158 844–848], and appears to use a Ca2+ -ATPase for Ca2+ extrusion. (c) Antiport driven by pmf or smf. A Ca2+ /H+ antiporter has been reported to operate in membrane vesicles of Bacillus subtilis for Ca2+ extrusion [JB (1985) 164 1294–1300]. Similar systems appear to function in E. coli and Azotobacter vinelandii for Ca2+ extrusion, while a Ca2+ /Na+ antiporter may occur in halophilic organisms (e.g. Halobacterium spp). Under some conditions the Na+ /H+ antiporter in E. coli can be driven by pmf, extruding Na+ and thus generating a SODIUM MOTIVE FORCE which can be used e.g. for melibiose uptake (Na+ /melibiose symport) and/or for the regulation of intracellular pH. However, in media of high pH, containing high concentrations of Na+ , the Na+ /H+ antiporter can generate pmf by proton extrusion [JB (1985) 163 423–429]. The K+ /H+ antiporter in E. coli is believed to function e.g. for the prevention of over-alkalinization of the cytoplasm in respiring cells. (d) Antiport coupled to ATP hydrolysis. An Na+ /K+ -ATPase (‘sodium pump’) occurs in eukaryotic cells but not in prokaryotic cells or in mitochondria; energy derived from ATP hydrolysis at this ATPase is used to pump Na+ out and K+ in – the Na+ /K+ exchange ratio probably being ca. 3:2. The sodium pump is used e.g. to maintain intracellular osmotic stability, and to generate the smf needed for the uptake of certain substrates; it is inhibited by ouabain. (e) Symport systems. In E. coli, LACTOSE is generally taken up by an H+ /lactose symport, while melibiose uptake involves an Na+ /melibiose symport. Bacillus subtilis, grown aerobically on citrate-containing media, can accumulate Ca2+ by a Ca2+ /citrate symport. An electrogenic H+ /lactate symport is used by some fermentative bacteria for energy conversion (see END-PRODUCT EFFLUX). In mitochondria, phosphate (Pi) uptake occurs by electroneutral symport with H+ . (f) Other ion transport systems. The so-called Trk system is responsible for much of the uptake of K+ in E. coli, and its activity is influenced by extracellular osmotic pressure. Trk is apparently not an ATPase, but it may be regulated by ATP or by a related compound [JGM (1985) 131 77–85]. ionizing radiation (in sterilization) Ionizing radiations (e.g. gamma-rays, beta-rays (electrons), X-rays) are used e.g. for the STERILIZATION of pre-packed medical and biological equipment such as surgical sutures, syringes, plastic Petri dishes, etc; currently they are not used to any great extent for the treatment of foodstuffs because they can cause toxicity and a deterioration in organoleptic properties in foods (but see FOOD PRESERVATION (g)). (See also SEWAGE TREATMENT.)

(1)

in which R is the gas constant, T is the absolute temperature, F is the Faraday constant, and m is the charge on the ion. This expression can be readily converted to the ion electrochemical ˜ Xm+ : potential gradient, 1m ˜ Xm+ = m1y − Z log10 1m

[Xm+ ]′′ [Xm+ ]′

(2)

where Z is the constant 2.3RT/F. When applied to the gradient of an ion which crosses the membrane by electrogenic or electrophoretic uniport, equation 2 gives a measure of the driving force (due to the gradient itself) tending to cause movement of that ion across the membrane. (When an ion is translocated across a membrane by antiport or symport mechanisms equation 2 must be modified so as to accommodate the additional forces acting on the ion.) If a proton gradient is maintained (imposed) across an energytransducing membrane (e.g. by the use of metabolic energy) it will influence the electrochemical equilibria of each of the various types of ion distributed across the membrane. A given cation which crosses the membrane by electrical uniport will tend to redistribute across the membrane so as to reach an electrochemical equilibrium with the membrane potential of the pmf. For example, in the case of the bacterial cytoplasmic membrane (interior negative) a given cation which, initially, is largely extracellular will tend to be accumulated within the cytoplasm; if the cation reaches electrochemical equilibrium, the Gibbs free energy associated with its gradient becomes zero (i.e., ˜ Xm+ = 0), and the relationship of the imposed membrane 1m potential to the intracellular and extracellular concentrations of the given cation is then given by the Nernst equation: 1y =

Z [Xm+ ]int log10 m+ m [X ]ext

(3)

Equation 3 is obtained by re-arranging equation 2 in the ˜ Xm+ = 0. special case when 1m In living cells, transmembrane ion translocation may affect either or both components of pmf. When ions are translocated by antiport or symport processes, the effect of such translocation on pmf depends e.g. on the stoichiometry of the process. For example, under some conditions the Na+ /H+ antiporter in Escherichia coli consumes pmf, H+ influx exceeding Na+ efflux. (Since the H+ /Na+ ratio is >1, operation of the antiporter in this mode consumes 1y as well as 1pH.) However, with high extracellular pH and Na+ the antiporter operates in such a way that H+ efflux is greater than Na+ influx – with consequent augmentation of pmf. Ion uptake or extrusion commonly leads to compensatory ion fluxes. Thus, e.g. in mitochondria the effects of pmf-dependent 405

b-ionone ring Ionizing radiations sterilize by supplying energy which permits a great variety of lethal chemical reactions to occur in contaminating organisms. In general, resistance to ionizing radiation increases in the order: multicellular organisms; Gram-negative bacteria; Gram-positive bacteria and moulds; bacterial endospores, viruses and viroids. Exceptions include e.g. Deinococcus radiodurans, which is more resistant than most or all bacterial endospores. Low (sublethal) doses of radiation can be mutagenic: e.g., in Escherichia coli the SOS SYSTEM – and hence error-prone (mutagenic) repair – may be induced. (In some cases, susceptibility to ionizing radiation is enhanced by the presence of water and/or oxygen.) Typically, toxins and other microbial products are more resistant than cells to ionizing radiations. Ionizing radiation may affect the materials being sterilized – e.g., a sterilizing dose of radiation can damage certain plastics. Large-scale industrial sterilization is generally carried out with either a source of gamma-rays or a source of high-energy electrons. In a gamma-radiation plant the source of radiation is 60 Co (cobalt-60): a radioactive isotope (half-life ca. 5.3 years) which provides both gamma-rays and (relatively) low-energy electrons. High-energy electrons (ca. 5–10 MeV) are produced in electron accelerators. The high-energy electron radiation used for sterilization carries more energy than does the gamma-radiation, although it has poorer powers of penetration; sterilization processes using high-energy electrons require exposures of the order of seconds, while those using gamma-rays require minutes or hours. The actual sterilizing dose used should, ideally, take into account e.g. the numbers and types of contaminants. In many countries the recommended minimum sterilizing dose is ca. 2.5 Mrad (25 kGy, see GRAY); a higher minimum is recommended in Scandinavia. X-rays (a form of electromagnetic radiation) have been used e.g. for sterilizing items of high density which are impermeable to a beam of high-energy electrons. [Quality assurance in radiation sterilization (theoretical treatment): JAB (1985) 58 303–313.] (See also ULTRAVIOLET RADIATION.) b-ionone ring See CAROTENOIDS. ionophore Any substance which actually or effectively increases the permeability of biological membranes (or of artificial lipid bilayers) to one or more types of ion. Channel-forming ionophores (e.g. GRAMICIDINS) form pores in the membrane; such ionophores typically exhibit little discrimination between different ions, and may allow the passage of up to ca. 107 ions per pore per second. Mobile carrier ionophores (e.g. PROTON TRANSLOCATORS) diffuse within the membrane; they can exhibit a high degree of specificity for ions. Mobile carriers may effect ion UNIPORT (see e.g. VALINOMYCIN) or ion ANTIPORT (see e.g. A23187 and NIGERICIN). (See also ENNIATINS, LASALOCID, MACROTETRALIDES, SALINOMYCIN and ION TRANSPORT.) Iotech process A process, involving explosive depressurization, in which the lignin–hemicellulose–cellulose complex from plant material is disrupted to release CELLULOSE for use as a feedstock in certain biotechnological processes (e.g. SINGLE-CELL PROTEIN or INDUSTRIAL ALCOHOL production). IP10 (chemokine) See CHEMOKINES. IpaA protein See DYSENTERY. IpaB protein See APOPTOSIS, DYSENTERY and PROTEIN SECRETION (type III systems). IPN virus (IPNV) The causal agent of INFECTIOUS PANCREATIC NECROSIS disease of salmonid fish. The virion has an unenveloped, icosahedral capsid (ca. 59 nm diam.) containing a

genome of two linear pieces of dsRNA (MWts ca. 2.3 × 106 and 2.5 × 106 ). Each strand of both RNA molecules is covalently linked by its 5′ end to a protein – the first known case of genome-linked protein in a dsRNA virus. A minor protein component (VP105) is reputed to have dsRNA-dependent RNA transcriptase activity. [Review: CJM (1983) 29 377–384.] Virus transmission occurs vertically and horizontally. IPNV is representative of a family of bisegmented dsRNA animal viruses, Birnaviridae [approved: Intervirol. (1986) 25 141–143], which includes the INFECTIOUS BURSAL DISEASE VIRUS of chickens, DROSOPHILA X VIRUS, and various ‘IPNV-like’ viruses isolated from freshwater and marine fish (e.g. Eel Virus European, EVE, isolated from Japanese eels: Anguilla japonica; see also SPINNING DISEASE) and from marine bivalve molluscs (e.g. oysters – Ostrea and Crassostrea spp – and Tellina tenuis). ipomeamarone The (+)-enantiomer of 2-methyl-2-(4-methyl-2oxopentyl)-5-(3-furyl) tetrahydrofuran: a PHYTOALEXIN produced by the sweet potato (Ipomoea batatas) in response to infection by certain fungal pathogens (e.g. the ‘black rot’ fungus Ceratocystis fimbriata). Ipomeamarone and its (−)-enantiomer ngaione (a normal constituent of certain trees and shrubs) are both hepatotoxic and can cause liver disease in livestock. (See also 4-IPOMEANOL.) 4-ipomeanol A substance, (1-(3-furyl)-4-hydroxy-1-pentanone), produced by the sweet potato (Ipomoea batatas) in response to infection by certain fungal pathogens. It is toxic to animals, causing pulmonary oedema and massive pleural effusion. Together with e.g. ipomeanine (a dihydro derivative of 4-ipomeanol) it may be the ‘lung oedema factor’ responsible for the fatal respiratory disease in livestock (especially cattle) which follows ingestion of mould-damaged sweet potatoes. (cf. IPOMEAMARONE.) iprodione See DICARBOXIMIDES. IPTG Isopropyl-b-D-thiogalactoside: a gratuitous inducer of the LAC OPERON. IQB INDIVIDUAL QUICK BLANCH. IR INVERTED REPEAT. Ir genes Immune response genes: genes, associated with the MHC, which determine the ability of a mouse to make humoral and cell-mediated immune responses to a wide range of antigens; certain of these genes encode the IA ANTIGENS. Irgasan DP 33 Syn. TRICLOSAN. Iridaea See RHODOPHYTA. iridescence Coloured light formed by interference when white light is reflected from both surfaces of a thin film. iridescent insect viruses See CHLORIRIDOVIRUS and IRIDOVIRUS. Iridia See FORAMINIFERIDA. Iridoviridae A family of icosahedral dsDNA-containing VIRUSes which infect invertebrates (mainly insects) and poikilothermic vertebrates. The family contains four genera: CHLORIRIDOVIRUS, IRIDOVIRUS, LYMPHOCYSTIVIRUS and RANAVIRUS. (cf. AFRICAN SWINE FEVER.) Virion: icosahedral (ca. 120–300 nm diam.) and complex in structure, consisting of a nucleoprotein core surrounded by a layer composed of a lipoprotein membrane beneath an icosahedral protein lattice. Some virions may have an additional lipoprotein ENVELOPE derived from the host cell plasmalemma or endoplasmic reticulum; the envelope is apparently not essential for infectivity. Virions are generally stable at pH 3–10 and at 4° C; they can be inactivated e.g. at 55° C for 15–30 min. Members of the genera Ranavirus and Lymphocystivirus are sensitive to ether and non-ionic detergents. Genome: one molecule (possibly two in some cases) of linear dsDNA (MWt ca. 100–250 × 106 ); in at least some iridoviruses 406

iron–sulphur proteins Listeria monocytogenes uses siderophores from other bacteria and various iron-chelating agents in the environment and mammalian hosts; a cell-surface ferric reductase may recognize all of these agents. A pathogen’s absolute need for iron has prompted the search for new vaccines that stimulate protective antibodies against the cell-surface receptors for iron-chelating agents. Pseudomonas aeruginosa can reduce PYOCYANIN to leucopyocyanin which, in turn, can reduce the (ferric) iron in iron– transferrin complexes [Inf. Immun. (1986) 52 263–270]; iron thus released from transferrin may be available to iron-limited bacteria. Virulence in the fish pathogen Vibrio anguillarum (see VIBRIO) depends partly on a plasmid-encoded siderophore, anguibactin. [Plasmid-mediated iron transport and bacterial virulence: ARM (1984) 38 69–89.] In plant-pathogenic Erwinia chrysanthemi, mutants defective in iron transport were non-pathogenic [JB (1985) 163 221–227]. [Iron metabolism in pathogenic bacteria: ARM (2000) 54 881–941.] Applied aspects. Siderophore-producing strains of Pseudomonas putida used for the BACTERIZATION of seed potatoes apparently increase the yield in short-rotation crops [NJPP (1986) 92 249–256]; thus, siderophores may modify the RHIZOSPHERE microflora in favour of the potato plant. Interestingly, some microbial ferrisiderophores are taken up by plants [see for example FEBS (1986) 209 147–151]. iron bacteria Bacteria whose growth is associated with the extracellular deposition of oxides or hydroxides of iron and/or manganese; such deposits usually cover or impregnate the bacterial capsule, sheath or stalk. Iron bacteria occur e.g. in various ironand manganese-containing soils and waters, and in water distribution systems (see also TUBERCLE (sense 2)). Evidence that the deposition of metal oxides/hydroxides is a direct result of microbial metabolism has not been obtained for the majority of the iron bacteria (cf. GALLIONELLA) – many of which have not even been grown in pure culture; the opportunity for biological oxidation of Fe2+ is relatively poor under aerobic conditions (in which Fe2+ undergoes rapid autoxidation) but becomes significant under microaerobic conditions, particularly at pH 5–6, in which autoxidation is slow. (Autoxidation of Mn2+ is slow below pH 9.) The iron bacteria include e.g. CLONOTHRIX, CRENOTHRIX, GALLIONELLA, LEPTOTHRIX, METALLOGENIUM, OCHROBIUM and SIDEROCAPSA; some authors include the acidophilic iron oxidizers, e.g. Thiobacillus ferrooxidans. [Review: ARM (1984) 38 515–550.] iron box See OPERATOR. iron corrosion See CATHODIC DEPOLARIZATION THEORY. iron–sulphur centre See IRON–SULPHUR PROTEINS. iron–sulphur proteins (Fe−S proteins) A category of iron- and sulphur-containing proteins which are widely distributed in cells of all types and which participate e.g. in electron transfer processes (see e.g. ELECTRON TRANSPORT CHAIN and NITROGENASE); except in rubredoxins (see later) each iron–sulphur protein contains two or more iron atoms linked to one another by an equal number of (acid-labile) sulphur atoms, the entire complement of iron and acid-labile sulphur forming one or more discrete iron–sulphur centres (= iron–sulphur clusters) linked to the protein typically by thiolate side-chains of cysteine residues. (See also RHODANESE.) Rubredoxins are traditionally included with the Fe−S proteins, although they contain only one iron atom and no acidlabile sulphur; the iron is linked to the protein via four thiolate

(Chilo iridescent virus, frog virus 3, lymphocystis virus) the DNA is circularly permuted and terminally redundant – features unique among animal viruses (but quite common among bacteriophages). The molecular biology of iridoviruses has been studied mainly in FROG VIRUS 3. Iridovirus (small iridescent insect virus group) A genus of viruses (family IRIDOVIRIDAE) which infect insects; infected larvae – and purified virus pellets – exhibit a blue iridescence. Virions (ca. 120 nm diam.) are ether-resistant. Type species: Chilo iridescent virus (insect iridescent virus type 6) [Intervirol. (1986) 25 141–143]. Other members include e.g. Tipula iridescent virus, which infects e.g. craneflies (Tipula spp) and many other insects, and insect iridescent viruses 1, 2, 9, 10 and 16–29. Probable member: Chironomus plumosus iridescent virus (C. plumosus is a type of non-biting midge, with haemoglobin-containing larvae known as ‘blood-worms’). Possible member: Octopus vulgaris disease virus. Irish moss See CHONDRUS. iron Most microorganisms need iron to form e.g. CATALASE, various oxidases, IRON–SULPHUR PROTEINS, ribonucleotide reductase, certain SUPEROXIDE DISMUTASES and/or CYTOCHROMES. Rarely – as e.g. in the type strain of Lactobacillus plantarum [FEMS (1983) 19 29–32] – iron is not an absolute requirement for growth. In many cases microorganisms synthesize and export SIDEROPHORES (q.v.) specifically for the sequestration and uptake of iron, particularly when iron is scarce. Theoretically, siderophores could behave simply as shuttles – remaining extracellular and delivering iron from the environment to the cell surface for internalization by a membrane TRANSPORT SYSTEM. However, in Escherichia coli, the siderophore enterochelin (= enterobactin) carries (ferric) iron into the cytoplasm in an energy-dependent uptake process – binding initially at the cell-surface FEPA PROTEIN; within the cytoplasm, cleavage of the siderophore (by an esterase) releases the iron. Fe3+ is reduced to Fe2+ . Some strains of E. coli produce aerobactin, a siderophore whose outer membrane receptor is the Iut protein. Interestingly, E. coli can also use iron–coprogen and iron–ferrichrome complexes (receptors: FhuE and FhuA (= TonA) proteins, respectively) – even though E. coli produces neither coprogen nor ferrichrome. E. coli can also take up iron–citrate complexes. Iron uptake: regulation. In e.g. E. coli, accumulation of intracellular Fe2+ results in binding of ferrous ions to the regulator FUR PROTEIN which then represses the expression of a number of genes (including fep). Iron in pathogenicity. Pathogens in animals must compete successfully with the host for available iron. [Iron in pathogenicity: RMM (1998) 9 171–178.] Thus, many pathogenic strains of E. coli secrete aerobactin; this promotes bacterial growth in extracellular concentrations of iron ca. 500-fold lower than those needed by the enterochelin system [Inf. Immun. (1986) 51 942–947]. Aerobactin seems able to compete successfully with the SIDEROPHILIN transferrin [Mol. Microbiol. (1994) 14 843–850]. For extracellular growth, Mycobacterium tuberculosis uses EXOCHELINs (which may obtain iron from siderophilins) and cellsurface ferric iron chelators: MYCOBACTINs (which internalize iron transferred from the exochelin). Some pathogens obtain iron directly from siderophilins; thus, e.g. Neisseria gonorrhoeae and N. meningitidis have receptors for human TRANSFERRIN. 407

ironophores ligands. A rubredoxin with an Em of ca. −60 mV occurs in Clostridium pasteurianum. (See also HYDROCARBONS.) Other iron–sulphur proteins contain, per molecule, one or more of the following types of centre: [2Fe−2S] (see also RIESKE PROTEIN), [3Fe−3S] (found e.g. in Azotobacter vinelandii ), and/or [4Fe−4S]; 2S, 3S and 4S refer specifically to acid-labile sulphur. Iron–sulphur proteins can be classified as either simple (e.g. rubredoxins, FERREDOXINS) or complex (= conjugated), the latter having additional prosthetic groups such as a flavin or haem or a non-iron metal atom (e.g. molybdenum). Complex iron–sulphur proteins include e.g. the sulphite reductase of Escherichia coli (EC 1.8.7.1), which includes four [4Fe−4S] centres together with molecules of FAD, FMN and sirohaem, and a chloroplast nitrate reductase (EC 1.7.7.1) containing one [4Fe−4S] centre and sirohaem. [Review: Book ref. 146, pp. 79–120.] ironophores Syn. SIDEROPHORES. Irpex See APHYLLOPHORALES (Polyporaceae). IRS Internal resolution site: see Tn3. IS element See INSERTION SEQUENCE. IS1 A 768-bp INSERTION SEQUENCE present e.g. in R plasmids (see also Tn9 ), the genome of BACTERIOPHAGE P1, the chromosome of Escherichia coli K12 (in multiple copies), etc. IS1 seems to transpose preferentially to target sites which are rich in AT, frequently cleaving at a GC pair within such a region. Transposition can apparently generate either 9- or 8-bp duplications of target DNA [PNAS (1985) 82 839–843]. IS1 encodes two genes, insA and insB, which are required for IS1-mediated transposition and cointegration. IS5 A 1195-bp INSERTION SEQUENCE present in the chromosome of Escherichia coli K12 strains; it has a high target specificity (see TRANSPOSABLE ELEMENT). IS10 An INSERTION SEQUENCE that has been found only in association with Tn10 (q.v.). IS50 See Tn5. IS101 A 209-bp INSERTION SEQUENCE which is defective and carries no genes; its transposition depends entirely on gdencoded transposase and resolvase functions (see Tn3 ). (cf. Tn951.) Its inverted repeat sequences are closely related to, but not identical with, those of gd. IS900 An INSERTION SEQUENCE reported to be specific to Mycobacterium paratuberculosis. IS900 has been used e.g. as a target for PCR-based detection of M. paratuberculosis in milk [AEM (1998) 64 3153–3158]. IS1000 Syn. gd (see Tn3 ). IS6110 An INSERTION SEQUENCE regarded as specific to members of the Mycobacterium tuberculosis complex (i.e. M. tuberculosis, M. bovis, BCG, M. africanum and M. microti ). The number of copies of IS6110 per genome varies with strain; a few strains of M. tuberculosis apparently lack the sequence, while most strains of M. bovis appear to contain only a single copy. Some 16 copies of IS6110 occur in the genome of the H37rv reference strain of M. tuberculosis [Nature (1998) 393 537–544]. Some authors have questioned the specificity of IS6110, indicating that a central region of the sequence is similar to a sequence in non-tuberculous mycobacteria [JCM (1997) 35 799–800]; others have affirmed the specificity of this sequence for members of the M. tuberculosis complex [JCM (1997) 35 800–801]. IS6110 has been widely used for TYPING isolates of M. tuberculosis. However, using SPOLIGOTYPING, some authors have found that, in a particular subset of multidrug-resistant

strains, the rate of transposition of IS6110 within the genome may be too high for reliable RFLP-based typing even over a period of a few years [JCM (1999) 37 788–791]. By contrast, others have reported that IS6110 -based typing gives insufficient discrimination [JCM (1999) 37 3022–3024]. isatin-b-thiosemicarbazone (IBT) An ANTIVIRAL AGENT. IBT and some of its derivatives (e.g. methisazone: N-methyl-IBT) inhibit the replication of poxviruses, apparently acting at a late stage in the replication cycle. Methisazone has been used prophylactically in cases of exposure to smallpox, and in the treatment of complications of smallpox vaccination. (See also THIOSEMICARBAZONES.) ISEM IMMUNOSORBENT ELECTRON MICROSCOPY. IS-GA See IN SITU PCR. ISH See PROBE. isidiate (lichenol.) Bearing or consisting of isidia (see ISIDIUM). isidium (lichenol.) A small protuberance (ca. 0.01–0.3 × 0.5–3.0 mm) which arises from the surface of the thallus in certain lichens; it consists of photobiont cells and medullary tissue, typically covered by a cortex, and may be e.g. spherical, flattened, cylindrical, branched (‘coralloid’), according to species. In many isidiate lichens the isidia are easily broken off and probably serve as propagules; in other cases they may serve to increase the surface area – and hence the assimilative capacity – of the thallus. islandic acid A water-soluble, acidic, extracellular, (1 → 6)-blinked glucan containing malonic acid residues; it is produced by Penicillium islandicum. islet-activating protein Syn. PERTUSSIS TOXIN. isoaccepting tRNA See TRNA. isoamylase See DEBRANCHING ENZYMES. isoantibody Any antibody formed against an antigen derived from a genetically different individual of the same species. isocitrate dehydrogenase See TCA CYCLE. isocitrate dehydrogenase kinase–phosphatase See TCA CYCLE. isocitrate lyase See TCA CYCLE and SERINE PATHWAY. isoconazole See AZOLE ANTIFUNGAL AGENTS. isodiametric Rounded or polyhedral: having roughly the same diameter in all directions. isoelectric focusing (IEF) A type of ELECTROPHORESIS in which amphoteric molecules (e.g. proteins) are separated from one another on the basis of their differing ISOELECTRIC POINTS (IEPs). In principle, a column of gel (e.g. polyacrylamide) containing a mixture of AMPHOLYTES (each with a different IEP) is subjected to an electrical potential difference until the ampholytes are distributed (according to their IEPs) to form a stable pH gradient. The sample (e.g. mixture of proteins) is then added and subjected to an electrical potential difference so that each protein migrates to the region corresponding to its IEP; proteins may then e.g. be stained in situ or removed from the gel. isoelectric point (IEP; pI) In substances (e.g. proteins) whose charge depends on the pH of the medium: the pH at which the molecule has no net charge and hence zero electrophoretic mobility. isoelectrofocusing Syn. ISOELECTRIC FOCUSING. isoenzyme (isozyme) One of a number of ENZYMES which catalyse the same reaction(s) but differ from each other e.g. in primary structure and/or electrophoretic mobility. (See also ZYMODEME.) isofloridoside 1-O-Glycerol-a-D-galactopyranoside: a storage and osmoregulatory glycoside in e.g. Poterioochromonas malhamensis and also (often with FLORIDOSIDE) in members of the Rhodophyta. 408

itraconazole isogamy The union of gametes which are alike in form and physiology. (cf. ANISOGAMY.) isogenic Refers to two or more organisms or cells which have identical genotypes. isoimmunization The stimulation of an immune response to antigens derived from another individual of the same species. (cf. HETEROIMMUNIZATION.) isokont Refers to a pair of flagella (on a biflagellate cell) which are similar in length and type. (cf. HETEROKONT.) isolation (1) (microbiol.) Any procedure in which a given species of organism, present in a particular sample or environment, is obtained in pure CULTURE. According to organism, isolation may involve e.g. culture on a selective MEDIUM, ENRICHMENT, and/or the use of techniques such as FILTRATION or MICROMANIPULATION. (2) (med., vet.) The separation of patient(s) or animals(s) from others in order e.g. to prevent the spread of disease. (See also QUARANTINE.) L-isoleucine biosynthesis Many microorganisms synthesize isoleucine by the pathway shown in Appendix IV(d). Certain bacteria generate a-oxobutyrate by alternative pathways: e.g., from L-glutamate in Escherichia coli, from L-methionine in obligately anaerobic bacteria, from pyruvate in Leptospira sp, and from propionate in Clostridium sporogenes [JGM (1984) 130 309–318, q.v. for refs]. isolichenin A linear a-D-glucan containing (1 → 3) and (1 → 4) linkages; it occurs in certain lichens (e.g. Cetraria islandica). (cf. LICHENIN.) isomaltose A reducing disaccharide: a-D-glucopyranosyl-(1 → 6)-D-glucopyranose. (cf. GENTIOBIOSE.) isomarticin See NAPHTHAZARINS. isomerases ENZYMES (EC class 5) which catalyse isomerizations (i.e., intramolecular rearrangements). They include e.g. epimerases (e.g. that catalysing the interconversion of Dribulose 5-phosphate and D-xylulose 5-phosphate), racemases (e.g. those catalysing L- and D-amino acid interconversions), etc. isometric labile ringspot viruses Syn. ILARVIRUSES. isometric ssDNA phages Syn. MICROVIRIDAE. isometric virus A virus in which the virion is more or less spherical, usually exhibiting ICOSAHEDRAL SYMMETRY. isomorphic Morphologically similar or identical. isomorphic alternation of generations See ALTERNATION OF GENERATIONS. isoniazid A synthetic ANTIBIOTIC, isonicotinic acid hydrazide (INH), bactericidal for actively growing cells of Mycobacterium tuberculosis, M. bovis and, to a lesser extent, other Mycobacterium species. INH is an important anti-TUBERCULOSIS drug whose function depends on prior activation by a catalase (KatG; katG gene product) within the bacterium; the activated drug apparently inhibits enzymic step(s) in the synthesis of essential cell-wall MYCOLIC ACID (Microbiology (2000) 146 289–296]). Resistance to isoniazid can follow mutation in any of several genes, including katG and ahpC ; isoniazid is used in combination therapy for the treatment of tuberculosis. (See also RISE-RESISTANT TUBERCULOSIS.) In M. tuberculosis, susceptibility to isoniazid, oxidative stress response and iron regulation are related features, but precise details of relationships remain to be elucidated [see TIM (1998) 6 354–358]. isopanose a-Maltosyl-(1 → 6)-D-glucose. isopenicillin N See PENICILLIN N. isopropanol See ALCOHOLS. isopropyl-b-D-thiogalactoside A gratuitous inducer of the LAC OPERON.

isopsoralen See PCR. isopycnic centrifugation See CENTRIFUGATION. isorenieratene See LIGHT-HARVESTING COMPLEX. isoschizomers RESTRICTION ENDONUCLEASES which recognize the same sequence in DNA but which are derived from different species. [Restriction endonucleases and their isoschizomers: NAR (1991) 19 2077–2109.] Isosphaera See BACTERIA (taxonomy). Isospora A genus of parasitic protozoa (suborder EIMERIORINA) which form disporic, tetrazoic oocysts (cf. e.g. EIMERIA); the genus, as originally defined, includes only homoxenous species, but it has been expanded by some authors [see AP (1982) 20 403–406] to include heteroxenous species which form disporic, tetrazoic oocysts (typically shed unsporulated) and which may form tissue cysts in the intermediate host. The expanded genus thus includes e.g. organisms otherwise placed in the genera BESNOITIA and TOXOPLASMA, as well as the obligately heteroxenous Isospora datusi (= Hammondia hammondi). For generalized homoxenous and heteroxenous life cycles see EIMERIORINA; see also COCCIDIOSIS (q.v. for refs). Isosticha See HYPOTRICHIDA. isosulfazecin See MONOBACTAMS. isotopic labelling (probe) See PROBE. Isotricha A genus of ciliates related to DASYTRICHA. isotype (class) Each of the five main variant forms (classes) of IMMUNOGLOBULIN (IgA, IgD, IgE, IgG and IgM); isotypes differ in the amino acid sequence in the constant region of their heavy chains. Immunoglobulins of all five isotypes occur in every normal individual (cf. ALLOTYPE). A given isotype may be divided into subclasses (distinguishable serologically). For example, there are several subclasses of IgG (designated IgG1, IgG2 etc.). isotype switching See ANTIBODY FORMATION. isovelleral See LACTARIUS. IsoVitaleX A commercial preparation – containing e.g. vitamin B12 , amino acids, purines, D-glucose, thiamine and TPP, NAD+ , Fe(NO3 )3 , PABA – used for the enrichment of media for isolating and/or cultivating fastidious bacteria (e.g. Haemophilus spp). isozyme Syn. ISOENZYME. Issatchenkia A genus of yeasts (family SACCHAROMYCETACEAE) which reproduce by multilateral budding; pseudomycelium is formed. Asci are persistent. Ascospores: spheroidal, roughsurfaced. Cells contain ubiquinone-7 (Q-7). Sugars may be fermented; NO3 − is not assimilated. A pellicle develops on liquid cultures. Species – I. occidentalis (anamorph: Candida sorbosa), I. orientalis (anamorph: Candida krusei ), I. scutulata, I. terricola – have been isolated from soil, fruit, etc. [Book ref. 100, pp. 214–223.] isthmus (biol.) Any narrow region connecting two structures in an organism or cell: see e.g. placoderm DESMIDS. iteron One of a number of repeated (‘reiterated’) nucleotide sequences which occur in and/or near the replication origin(s) in certain plasmids – e.g. the F PLASMID and the R6K PLASMID. Itersonilia A genus of fungi incertae sedis; the organisms form mycelium containing CLAMP CONNECTIONS, and it has been suggested that I. perplexans forms a one-spored basidium [TBMS (1983) 80 365–368]. itraconazole A clinically useful AZOLE ANTIFUNGAL AGENT (a triazole); it has a high MWt and is highly lipophilic. Itraconazole has a broad spectrum of activity, inhibiting yeasts, dimorphic fungi and filamentous fungi; it appears to be less toxic to mammalian tissues than e.g. miconazole or ketoconazole owing 409

IUB IVET (in vivo expression technology) A technique used for detecting those genes (of a pathogen) which are transcribed only during infection of the host; such genes may be virulence genes, and this can be studied further e.g. by animal tests involving strains of the pathogen which are mutant for the given gene. IVET is outlined in the figure. [Some examples of IVET: TIM (1997) 5 509–513. Behaviour of bacteria in the host, and the methodology for studying it: TIM (1998) 6 239–243.] IVS (mol. biol.) Intervening sequence (= intron): see SPLIT GENE. iwatake The edible lichen Umbilicaria esculenta.

to its much higher selectivity for the fungal rather than the mammalian cytochrome P-450. [Review: Arch. Derm. (1986) 122 399–402.] [Pharmocology of itraconazole (review): Drugs (2001) 61 (supplement 1) 27–37.] IUB International Union of Biochemistry. iucA–iucD genes See SIDEROPHORES. IUdR See IDOXURIDINE. IUPAC International Union of Pure and Applied Chemistry. iutA gene See SIDEROPHORES. ivanolysin See THIOL-ACTIVATED CYTOLYSINS.

Population of small cccDNA molecules, constructed in vitro , each containing (in order of transcription): Population of cells of the pathogen

(1) a random fragment of the pathogen's chromosome (2) a promoter −less gene encoding chloramphenicol acetyltransferase (3) a promoter −less gene encoding β-galactosidase

Population of recombinant cells of the pathogen used to infect a test animal whose food has been supplemented with chloramphenicol

Recover the bacteria from test animal and plate on a medium containing Xgal; select white colonies

IVET (in vivo expression technology): the principle (diagrammatic). The figure shows one of several forms of IVET. IVET detects those genes of a pathogen whose expression is induced during (and only during) infection of the host animal. Vector molecules (see top, right) are inserted, by transformation, into a population of cells of the pathogen. In each transformed cell, the (random) fragment of chromosome in the vector inserts into the corresponding part of the pathogen’s chromosome (by an ‘insertion–duplication’ mechanism); because the vector molecules contain different fragments of the chromosome they will insert into different chromosomal sites in different cells – forming a heterogeneous population of recombinant cells. In some recombinant cells, the vector’s two promoter-less genes will have been inserted ‘in frame’ with an upstream promoter. In such cells, both of these genes will be transcribed if the promoter is active. The recombinant cells of the pathogen are used to infect a test animal whose food contains the antibiotic chloramphenicol (to which the pathogen is normally susceptible). Under these conditions, a recombinant cell can grow only if it produces chloramphenicol acetyltransferase (CAT), i.e. only if the CAT gene (in the vector molecule) is controlled by an active promoter; thus, the fact that a given recombinant cell grows within the animal indicates that its CAT gene is controlled by a promoter which is active within the test animal. (Because synthesis of CAT points to an active promoter, the CAT gene is sometimes called a ‘reporter’ gene.) Cells producing CAT can form large populations which greatly outnumber cells that do not form CAT. We need to know whether the promoter controlling an expressed CAT gene is active only when the pathogen is in the test animal – or whether it is also active when the pathogen is cultured (e.g. on agar media). If active only in the test animal, this indicates that the gene normally controlled by that promoter is induced during infection; such a gene is of interest because of its possible association with virulence. To study promoter activity further, the recovered bacteria are plated on a medium which lacks chloramphenicol but which contains the agent XGAL (q.v.); all the cells will grow. If a given promoter is active in culture then b-galactosidase will be formed and will give rise to a blue-green colony; such a colony tells us that activation of the given promoter does not occur only within the test animal. A white (lac− ) colony indicates that b-galactosidase (and CAT) can be formed only within the test animal, i.e. the relevant promoter is active only when the pathogen is actually infecting the animal. The gene which is normally controlled by this promoter can be isolated, cloned and sequenced and examined for its role in virulence. Reproduced from Bacteria, 5th edition, Figure 11.3, pages 304–305, Paul Singleton (1999) copyright John Wiley & Sons Ltd, UK (ISBN 0471-98880-4) with permission from the publisher.

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J J chain A cystine-rich polypeptide (MWt ca. 15000) involved in the formation of dimeric and polymeric forms of both IgA and IgM (q.v.). In an IgA dimer the J chain forms a link between cystine residues situated near the C-terminal ends of the heavy chains in the two monomers. jaagsiekte (pulmonary adenomatosis) A SHEEP DISEASE characterized by chronic progressive pneumonia in which the alveolar spaces become occluded by adenomatous ingrowths of the epithelium; the causal agent(s) appear to be viral (a herpesvirus and/or a retrovirus), but the causal agent of MAEDI is not involved. Incubation period: 1–3 years. Symptoms: dyspnoea, emaciation, and a profuse watery nasal discharge which may contain hyperplastic adenomatous epithelial cells; fever and inflammation are absent. Death occurs within ca. 4 months. [Book ref. 33, pp. 807–808.] Jaccard coefficient See entry SJ . jack bean lectin CONCANAVALIN A. jack-in-the-box ascus Syn. BITUNICATE ASCUS. Jacquard coefficient See entry SJ . JAK See CYTOKINES. janiemycin A polypeptide ANTIBIOTIC which inhibits transglycosylation in PEPTIDOGLYCAN synthesis. Janthinobacterium A genus of Gram-negative, strictly aerobic, catalase-positive, chemoorganotrophic bacteria which occur e.g. in soil and water; the organisms are motile (flagellated) rods, 0.8–1.2 × 2.5–6.0 µm. Metabolism is respiratory (oxidative); acid (no gas) is formed from e.g. glucose. Growth occurs in/on simple media (e.g. peptone water); violet, often gelatinous, colonies are formed on nutrient agar. Optimum growth temperature: 25° C, maximum 32° C. MR −ve; VP −ve; usually oxidase +ve. GC%: ca. 61–67. Type species: J. lividum (formerly Chromobacterium lividum). [Book ref. 22, pp. 376–377.] Janus green A blue basic DYE which has both azine and azo chromophores; it is used e.g. in VITAL STAINING. Janus kinase See CYTOKINES. Japanese B encephalitis (Japanese encephalitis; Russian autumn encephalitis) A viral ENCEPHALITIS which affects man, pigs and horses; it occurs in epidemics in e.g. Japan, China, Korea and parts of India. The disease is usually acute, but may run a protracted course with acute exacerbations. The causal agent is a flavivirus (see FLAVIVIRIDAE) which occurs e.g. in wild birds and is transmitted by mosquitoes (usually Culex sp). An inactivated vaccine has been used in Japan. [Review: ARM (1986) 40 395–414.] Japanese river fever Syn. SCRUB TYPHUS. Japonochytrium See THRAUSTOCHYTRIDS. Jarisch–Herxheimer reaction (Herxheimer reaction) A potentially fatal reaction which may follow the first effective chemotherapy against e.g. brucellosis or syphilis – or, in general, diseases caused by certain bacteria (particularly spirochaetes) and protozoa. Symptoms (e.g. an initial rise in temperature) are associated with a cascade of CYTOKINES which seem to be responsible for at least some of the pathophysiology. [Review: BCID (1994) 1 65–74.] The reaction has been prevented by treatment with antibodies against tumour necrosis factor (TNF) [NEJM (1996) 335 311–315]. jarrah dieback A disease of the jarrah (Eucalyptus marginata) – an important timber tree e.g. in Western Australia; the causal agent is generally believed to be Phytophthora cinnamomi, but

waterlogging of the soil may be an important contributory factor [New Phyt. (1985) 101 743–753]. (See also TREE DISEASES.) javanicin See NAPHTHAZARINS. JC virus See POLYOMAVIRUS. JCM Japanese Collection of Microorganisms, Riken, Wako-shi, Saitama 351, Japan. jelly fungi Those fungi of the TREMELLALES (e.g. Exidia glandulosa, Tremella mesenterica) which form gelatinous fruiting bodies – or all fungi (including e.g. Auricularia spp) which do so. jelly lichens Gelatinous lichens e.g. of the genera COLLEMA, LEMPHOLEMMA, LEPTOGIUM. Jembrana disease A CATTLE DISEASE, involving e.g. fever, generalized lymphadenopathy, nasal discharge, haemorrhage and splenomegaly; it was formerly assumed to be a tick-borne rickettsial disease but is now known to be caused by the bovine immunodeficiency virus. jet loop fermenter A LOOP FERMENTER in which culture is continually withdrawn from the column and pumped back (together with air/gas) via a nozzle at the base of the DRAFT TUBE; this promotes liquid circulation and dispersion of the injected gas. In the plunging jet design of the Vogelbusch IZ fermenter, re-cycled culture (and air) is introduced under pressure at the top of the column (which lacks a draft tube); this design achieves a high level of dissolved oxygen. Jew’s ear fungus See AURICULARIA. Jeyes fluid A household and horticultural DISINFECTANT consisting of coal tar acids solubilized with a soap prepared from pine resin and alkali. Jirovecella See ASTOMATIDA. JK coryneforms Coryneform bacteria which are resistant to (usually many) antibiotics; they are being increasingly reported as causes of serious nosocomial infections in immunosuppressed patients and patients with implants (pacemakers, prosthetic heart valves, etc). [Biochemical and cultural characteristics: JCP (1986) 39 654–660.] Johne’s bacillus Mycobacterium paratuberculosis. Johne’s disease (chronic bacillary diarrhoea; paratuberculosis) A chronic intestinal CATTLE DISEASE which may also affect other ruminants (e.g. sheep, goats, deer); it occurs worldwide and is caused by Mycobacterium paratuberculosis. Infection occurs on ingestion of contaminated water, grass etc. In cattle, the incubation period is long (usually more than 12 months); symptoms are uncommon in animals under 2 years old. The pathogen multiplies in the intestinal wall which becomes thickened and poorly absorptive; scouring is at first intermittent but becomes persistent and severe. The animal becomes emaciated and anaemic. There is no effective treatment. In goats, the mesenteric lymph nodes become oedematous and there is emaciation, but scouring is not a feature [VR (1983) 113 464–466]. In sheep, the disease involves emaciation but not scouring. joint-breaker fever Syn. O’NYONG-NYONG FEVER. joint-ill (vet.) In e.g. calves, foals and lambs: lameness involving inflammation of the articular surfaces of the joints, caused by any of a variety of organisms – e.g. Actinobacillus equuli, Actinomyces pyogenes, Erysipelothrix rhusiopathiae (particularly in piglets), salmonellae, Staphylococcus aureus. joint molecule (mol. biol.) A term sometimes used to refer to a structure composed of two dsDNA molecules held together only 411

Jones–Mote sensitivity juglone (5-hydroxy-1,4-naphthoquinone) A compound produced in the leaves and roots of walnut trees (Juglans spp); it has antifungal and antibacterial activity, and its presence in the tree may play a role in resistance to disease. [Juglone as a transcription-blocking agent: NAR (2001) 29 767–773.] jumping gene Syn. TRANSPOSABLE ELEMENT. juncopox virus See AVIPOXVIRUS. junctional pore complex (JPC) A carbohydrate-export apparatus, reported to occur in certain motile cyanobacteria, which (in at least some cases) includes a tubular structure (minimum diameter 13 nm) that is capable of spanning the cell envelope. It has been suggested that JPCs form the mechanistic basis of GLIDING MOTILITY in cyanobacteria [JB (2000) 182 1191–1199]. jungle yellow fever See YELLOW FEVER. Jun´ın virus See ARENAVIRIDAE and ARGENTINIAN HAEMORRHAGIC FEVER. junior synonym See SYNONYM. jute retting See RETTING.

by hydrogen bonding – as e.g. in early intermediates formed during homologous RECOMBINATION. Jones–Mote sensitivity (cutaneous basophil hypersensitivity) A form of hypersensitivity which may develop e.g. when a human subject is primed with a soluble protein antigen, or a guinea pig is primed with a protein in incomplete Freund’s adjuvant; subsequent challenge with the relevant allergen (within a few days of priming) leads to a weak, non-indurated, erythematous skin reaction in which the lesion contains a high proportion of BASOPHILS. (These reponses do not occur in mice.) Jones–Mote sensitivity can be transferred to a non-primed animal by serum (cf. DELAYED HYPERSENSITIVITY). Jonesia A genus which contains the former species Listeria denitrificans [IJSB (1987) 37 266–270]. Jopling reactions See LEPROSY. JPC See JUNCTIONAL PORE COMPLEX. Jud. Comm. JUDICIAL COMMISSION. Judicial Commission A taxonomic body concerned with the interpretation and/or amendment of the rules of microbial nomenclature.

1. Words in SMALL CAPITALS are cross-references to separate entries. 2. Keys to journal title abbreviations and Book ref. numbers are given at the end of the Dictionary. 3. The Greek alphabet is given in Appendix VI. 4. For further information see ‘Notes for the User’ at the front of the Dictionary.

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K K Lysine (see AMINO ACIDS). K antigens Capsular antigens – usually capsular polysaccharides (see CAPSULE). Examples include the capsular antigens of Streptococcus pneumoniae, COLOMINIC ACID, and VI ANTIGENS. In Gram-negative bacteria, K antigens can mask O ANTIGENS; in some bacteria the K antigens can be removed by heating (see e.g. VI ANTIGEN), but in others (e.g. Klebsiella spp) they are heat-stable. In Escherichia coli, several surface antigens originally designated K – e.g. K88, K99 – are actually (proteinaceous) fimbrial antigens, and it has been proposed that they be renamed F antigens (K88 = F4, K99 = F5) [Book ref. 68, pp. 61–64]; polysaccharide K antigens may occur together with fimbrial antigens in certain strains of E. coli. (See also ETEC and TEICHOIC ACIDS.) K+ -ATPase See ION TRANSPORT. K cells Killer cells: lymphoid cells which have cytotoxic/cytolytic activity against target cells; syn. NK CELLS. K+ pump See ION TRANSPORT. K+ transport See ION TRANSPORT. K virus See POLYOMAVIRUS. K vitamins See QUINONES. K1 killer strain (of Saccharomyces cerevisiae) See KILLER FACTOR. K1 RNA, K2 RNA See RNASE P. K88, K99 In Escherichia coli : fimbrial antigens of certain strains pathogenic in animals – see ETEC, FIMBRIAE and K ANTIGENS. Kabackosome A type of vesicle formed by the hypotonic lysis of a SPHAEROPLAST. A Kabackosome (which contains little or no cytoplasm) is composed of CYTOPLASMIC MEMBRANE; the inner and outer faces of the membrane correspond to those in the original cell. (cf. ETP.) KAF Syn. FACTOR I. Kaffir pox See SMALLPOX. Kagami fever See EHRLICHIA. Kahn test A STANDARD TEST FOR SYPHILIS. kala-azar See VISCERAL LEISHMANIASIS. Kanagawa phenomenon The phenomenon in which those strains of Vibrio parahaemolyticus isolated from human patients exhibit clear (b) haemolysis when grown on WAGATSUMA AGAR containing human RBCs but not on that containing horse RBCs (a Kanagawa +ve reaction), while almost all strains isolated from other sources, including food suspected of causing V. parahaemolyticus food poisoning, do not (i.e. are Kanagawa −ve). (Discoloration (a-haemolysis) and clear haemolysis on both human and horse RBC-containing media are both regarded as Kanagawa −ve results.) The Kanagawa haemolysin is heatstable, extracellular, cytotoxic and cardiotoxic, and is haemolytic for human, dog and rat RBCs, weakly so for rabbit and sheep RBCs, and inactive against horse RBCs. In feeding experiments (in man), only Kanagawa +ve strains were capable of causing gastroenteritis, but the role of the haemolysin in pathogenesis is unknown; Kanagawa +ve strains appear to be better able to multiply in the intestine than are Kanagawa −ve strains. (See also FOOD POISONING (h).) kanamycin Any of several related AMINOGLYCOSIDE ANTIBIOTICS (kanamycins A, B, C) produced by Streptomyces kanamyceticus; the drug used clinically is composed mainly of kanamycin A. kanchanomycin (albofungin) A complex polycyclic ANTIBIOTIC, produced by Streptomyces sp, which has both antibacterial

and antitumour activity. In the presence of divalent cations, kanchanomycin binds to DNA and inhibits DNA and RNA synthesis. Kaposi’s sarcoma (KS) A rare multifocal neoplastic disease which occurs in two forms: (i) slow and indolent (limited mainly to the skin), and (ii) rapid and fulminant (involving skin and gastrointestinal tract). The milder form occurs in certain ethnic groups (e.g. Ashkenazi Jews). The aggressive form occurs in children in tropical Africa and is also a common feature in HIVinfected patients. (Note that Kaposi’s sarcoma occurs also in some immunosuppressed transplant patients.) Kaposi’s sarcoma appears to be associated with human (gamma) herpesvirus 8 (HHV8) [see e.g. Lancet (1997) 349 558–563] in conjunction with the immunosuppressive effects of HIV. [PCR-based investigation of HHV8 in KS biopsies: Am. J. Path. (1997) 150 147–153.] Activation of latent HHV8 in vitro has been achieved by demethylation of the promoter of a transactivator region by means of the reagent tetradecanoylphorbol acetate (TPA), and studies on the level of methylation of the transactivator region in biopsies have suggested a relationship between methylation status and the development of HHV8associated disease [PNAS (2001) 98 4119–4124]. Kaposi’s varicelliform eruption May refer either to eczema herpeticum or eczema vaccinatum (see ECZEMA). kappa chain See LIGHT CHAIN. kappa particles See CAEDIBACTER. Karatomorpha See PROTEROMONADIDA. K¨arber method See END-POINT DILUTION ASSAY. Karelian fever See SINDBIS VIRUS. Karnal bunt (partial bunt; new bunt) A wheat disease caused by Neovossia indica (formerly e.g. Tilletia indica); originally a minor disease confined to NW India, it has recently spread through northern India and has become established in Afghanistan, Iraq, Pakistan, and Mexico, apparently transmitted on and in wheat seed. Usually only some of the grains in an ear are attacked; infected parts of the grain are initially grey but gradually turn black and emit a foul odour (trimethylamine). [Bot. Rev. (1983) 49 309–330.] (See also COMMON BUNT.) karyogamy The coalescence of nuclei (cf. PLASMOGAMY). karyogram See KARYOTYPE. karyokinesis Syn. MITOSIS. karyological relict (ciliate protozool.) Any present-day ciliate whose characteristics (particularly nuclear constitution) resemble those of (presumably) phylogenetically ancient ciliates. (See also KARYORELICTID GYMNOSTOMES and PRIMOCILIATID GYMNOSTOMES.) karyolysis (histopathol.) The dissolution of a cell’s nucleus with consequent loss of affinity for basic dyes. (cf. KARYORRHEXIS.) karyomastigont A nucleus together with its associated flagellum (or flagella) and, when present, axostyle. (See also DIPLOMONADIDA.) karyomere See MACRONUCLEUS. karyonide (caryonide) (ciliate protozool.) A clone of cells in which all the macronuclei have been derived from the same macronucleus. karyoplast A nucleus which has been isolated from a (eukaryotic) cell and which is enclosed within a sac of cytoplasmic membrane containing a small amount of cytoplasm. (cf. CYTOPLAST.) 413

karyorelictid gymnostomes Kawasaki disease An acute, occasionally fatal, febrile disease of unknown cause which affects infants and young children. Kawasaki disease may be a manifestation of an immune-complex-mediated systemic vasculitis [ADC (1984) 59 405–409]; more recently it has been suggested that at least some of the symptoms may be due to a SUPERANTIGEN. kb (kilobase) Of a DNA or RNA strand: a unit of length equal to 103 bases; the unit may also be used for 103 base pairs (bp) in dsDNA or dsRNA – although kbp (kilobase-pairs) is also used in this context. kbp See previous entry. Kcat mechanism See PHASEOLOTOXIN. KCN broth (cyanide broth; Møller’s [= Moeller’s] cyanide medium; potassium cyanide broth) A MEDIUM used in the CYANIDE TEST; it consists of an aqueous solution of peptone (1.0%), NaCl (0.5%), KH2 PO4 (0.0225%), Na2 HPO4 (0.56%), and KCN (0.0075%). The medium may be stored at 4° C for up to ca. 2 weeks. KCN test See CYANIDE TEST. kDa Kilodalton: 103 DALTONS. kDNA KINETOPLAST DNA. KDO See LIPOPOLYSACCHARIDE. Kdp system See ION TRANSPORT. kefir A fermented milk beverage made in parts of Russia, Bulgaria and the former Yugoslavia. Milk is fermented by a mixed and varied population of organisms which usually include lactobacilli [SAAM (1983) 4 286–294; JAB (1984) 56 503–505], Lactococcus lactis, and yeasts (for example, Saccharomyces spp); lactic acid, ethanol and carbon dioxide (which causes foaming) are the main products. The organisms become embedded in an extracellular polysaccharide (kefiran) to form whitish, gelatinous granules [scanning electron microscopy: JAB (1980) 48 265–268] which are carried to the surface by bubbles of carbon dioxide. The granules are collected and used as an inoculum for subsequent fermentations; they can be stored for several days in cold milk or water. (See also DAIRY PRODUCTS.) kefiran See KEFIR. Kellogg classification (of Neisseria gonorrhoeae) An early classification based on e.g.: (i) appearance of colony; (ii) autoagglutinability; and (iii) virulence. Types T1 and T2 correspond to fimbriate, virulent strains, while types T3 and T4 correspond to afimbriate, non-virulent strains. keloidal blastomycosis Syn. LOBOMYCOSIS. kelp (1) Any of various seaweeds that are used to obtain kelp (sense 2). (2) The ashes obtained by burning various large brown seaweeds such as Ascophyllum, Fucus, Laminaria, Macrocystis; such ashes have been used as an agricultural fertilizer and as a source of iodine, potash and soda (sodium carbonate). Kelsey–Sykes test A CAPACITY TEST used to determine the efficacy of each of several dilutions of a given disinfectant under simulated practical conditions. (cf. USE-DILUTION TEST.) To 3 ml of a given dilution of disinfectant is added a 1-ml aliquot of bacterial suspension at times 0, 10 and 20 min; at 8, 18 and 28 min the disinfectant is subcultured to each of five tubes of nutrient broth which are then incubated to detect the presence or absence of viable bacteria. A given dilution passes the test if no growth is obtained in at least two of the five tubes inoculated from it at 8 and 18 min. The test organism used is Pseudomonas aeruginosa NCTC 6749, Proteus vulgaris NCTC 4635, Escherichia coli NCTC 8196 or Staphylococcus aureus NCTC 4163; in a given test the organism used is that which is the most resistant to the test disinfectant. To examine the efficacy of the disinfectant under ‘dirty’ conditions a yeast

karyorelictid gymnostomes Presumptively primitive ciliates (subclass GYMNOSTOMATIA, order Karyorelictida) which contain diploid, non-dividing macronuclei; genera include e.g. Geleia, KENTROPHOROS, LOXODES, Remanella and Tracheloraphis. karyorrhexis (histopathol.) The fragmentation of a cell’s nucleus (cf. KARYOLYSIS; PYKNOSIS). karyoskeleton Syn. NUCLEOSKELETON. karyosome A NUCLEOLUS or nucleolus-like body. karyotic (of cells) Nucleated. karyotype The chromosomal constitution of a (eukaryotic) cell in terms of the number, size and morphology of the chromosomes at metaphase. A systematized diagrammatic representation of a karyotype is called an idiogram; a systematized photographic representation may be referred to as an idiogram or as a karyogram. kasugamycin An atypical AMINOGLYCOSIDE ANTIBIOTIC whose molecule contains neither streptidine nor deoxystreptamine. Kasugamycin is bacteriostatic and is also active against certain fungi (e.g. Pyricularia oryzae and Rhizoctonia solani ). kat See KATAL. Kata virus See PESTE DES PETITS RUMINANTS. Katadyn silver Metallic SILVER – containing traces of impurities (gold, palladium etc) – deposited on sand (or other filtering medium) used for the filtration and disinfection of water; the impurities facilitate ionization of the silver. katal (abbrv. kat) A unit of enzyme activity: that which increases the rate of conversion of a given chemical reaction by one mole per second under defined conditions. katG gene See ISONIAZID. Katodinium See DINOFLAGELLATES. Kauffmann–White classification A scheme for the classification and identification of the numerous serotypes of SALMONELLA (e.g. for epidemiological purposes). Each serotype is defined by its O ANTIGENS and, where applicable, its H ANTIGENS and VI ANTIGENS, and is given a specific ANTIGENIC FORMULA which indicates the nature of these antigens in the order O, Vi (if present) : H phase 1 : H phase 2. For example, S. typhi is designated by the formula 9, 12, [Vi]:d:–. This means that the organism has O antigens 9 and 12, may have Vi antigen (variable presence indicated by [ ]), and has phase 1 flagellar antigen d and no phase 2 flagellar antigen (indicated by a dash) – i.e. PHASE VARIATION does not occur in this serotype. The antigenic formula for S. panama is 1, 9, 12:1, v:1, 5 where 1, 9 and 12 are O antigens, and either phase 1 flagellar antigens 1 and v or phase 2 flagellar antigens 1 and 5 may be present; this serotype has no Vi antigen. Underlining (as in O antigen 1 in S. panama) indicates that the antigen is present as a result of BACTERIOPHAGE CONVERSION. (Phage conversion may lead to a change in serotype: thus, e.g., S. anatum, 3, 10:e, h:1, 6, may be converted to S. newington, 3, 15:e, h:1, 6. Similar effects can occur in bacteria of other genera, including e.g. Shigella [serotpe-converting bacteriophages and O-antigen modification in Shigella flexneri : TIM (2000) 8 17–23].) For further examples of antigenic formulae see SALMONELLA. (See also SMOOTH–ROUGH VARIATION.) Serotypes thus identified are placed into groups (O groups), the serotypes in each group having in common at least one major O antigen (the group antigen) which is not found in members of any other group. For example, the group antigen of group A is O antigen 2; that of group B is O antigen 4; group C, O antigen 6; group D, O antigen 9; group E, O antigen 3. Thus, both S. typhi and S. panama are group D strains. (Minor O antigens may occur in more than one group: e.g., O antigen 12 occurs in strains from groups A, B and D.) 414

Kineosporia kidney stones (in humans) See UROLITHIASIS kieselguhr Syn. DIATOMACEOUS EARTH. kievitone An isoflavonoid PHYTOALEXIN produced by the French bean (Phaseolus vulgaris). Cell-free extracts of Rhizoctonia solani elicit high levels of kievitone from excised bean hypocotyls, but those of Fusarium solani elicit only trace amounts. Kievitone can be converted to the less fungitoxic kievitone hydrate by an extracellular enzyme produced by Fusarium solani f.sp solani. Kilham rat virus See PARVOVIRUS. killed vaccine Syn. INACTIVATED VACCINE. killer cells (immunol.) Commonly refers to NK CELLS (q.v.) but may also refer e.g. to cytotoxic T cells. killer factor Any of several protein toxins secreted by ‘killer’ strains of Saccharomyces cerevisiae and encoded by one of two cytoplasmically co-inherited dsRNA elements; the K1 toxin (formed by K1 or type 1 killer strains) binds initially to a cell wall D-glucan of a sensitive cell and then transfers to the cytoplasmic membrane where it disrupts the membrane potential. One of the dsRNA elements (designated M) encodes both the toxin and an ‘immunity protein’ which confers on the producing cell immunity to the toxin; the toxin contains two subunits, a and b, both derived by proteolytic processing of a precursor polypeptide during toxin secretion. The precursor polypeptide apparently functions as the immunity protein – possibly by competing with the mature toxin for binding sites on the membrane [Cell (1986) 46 105–113]. The other dsRNA element (designated L) encodes a protein required for the (separate) encapsidation of M and L. The encapsidated particles (termed VLPs: virus-like particles) are variously regarded as plasmids or as viruses (Saccharomyces cerevisiae viruses, ScVs – see MYCOVIRUS). [Review: MR (1984) 48 125–156.] (cf. KILLER PLASMIDS; see also BACTERIOCIN.) killer helper factor Syn. INTERLEUKIN-2. killer paramecia Strains of Paramecium which are able to kill other (‘sensitive’) paramecia. See: CAEDIBACTER, LYTICUM, MATE KILLER, PSEUDOCAEDIBACTER, R BODY, SPIN KILLING. (cf. TECTIBACTER.) killer plasmids (in yeasts) In some strains of Kluyveromyces marxianus var. lactis the cells contain multiple copies of each of two linear, cytoplasmically inherited dsDNA plasmids, pGl1 and pGl2; cells containing these plasmids secrete a glycoprotein toxin capable of killing other (sensitive) strains of e.g. Candida, Kluyveromyces and Saccharomyces by inhibiting adenylate cyclase activity. These plasmids can be transferred to Saccharomyces cerevisiae (e.g. by protoplast fusion) on which they confer the killer phenotype. [ARM (1983) 37 253–276.] (cf. KILLER FACTOR.) killer yeasts See KILLER FACTOR and KILLER PLASMIDS. kilobase See entry kb. kimchi A Chinese and Korean food made by the lactic acid fermentation of vegetables (usually cabbage or radishes). Preparation resembles that of SAUERKRAUT. KinA, KinB See ENDOSPORE (sense 1). kinase An ENZYME which catalyses the transfer of a phosphate group from one substrate (commonly ATP) to another; examples include hexokinase and pyruvate kinase (both involved in the Embden–Meyerhof–Parnas pathway: see Appendix I(a)), ADENYLATE KINASE, and PPi:phosphofructose dikinase (see PYROPHOSPHATE). Kineosporia A genus of bacteria (order ACTINOMYCETALES, wall type I). The organisms form a substrate mycelium but no aerial hyphae; sporangia, each containing one zoospore, develop on

suspension is incorporated in each dilution of the disinfectant. The test conditions are standardized – e.g. the bacteria, yeast and disinfectant are each diluted in standard hard water. [PJ (1974) 213 528–530.] Kemerovo subgroup See ORBIVIRUS. kennel cough See MASTADENOVIRUS. Kentrophoros A genus of marine ciliates (subclass GYMNOSTOMATIA) related to LOXODES. Cells: very elongated and flattened (ribbon-like), ciliated only on one side, and associated with ectosymbiotic bacteria; there is no cytostome. keratin A highly insoluble protein found e.g. in hair, wool, horn, skin, feathers. Keratin is degraded by relatively few organisms – e.g. Candida albicans, DERMATOPHYTES. (See also PILIMELIA and THERMOMONOSPORA.) keratitis Inflammation of the cornea. (cf. KERATOCONJUNCTIVITIS; see also INFECTIOUS KERATITIS.) keratoconjunctivitis Inflammation of the cornea and conjunctiva. It may be caused e.g. by Chlamydia trachomatis (see e.g. TRACHOMA), Staphylococcus aureus, HERPES SIMPLEX virus, or adenoviruses (see e.g. EPIDEMIC KERATOCONJUNCTIVITIS). keratomycosis KERATITIS due to a fungus; it is usually due to an opportunist pathogen (e.g. Aspergillus spp, Candida spp). kerion (exudative ringworm; tinea kerion) A severe form of RINGWORM (usually tinea capitis) in which the dry, scaling skin lesions become inflamed and suppurative. kerogen Solvent-insoluble, condensed (i.e., covalently crosslinked and/or aromatized) organic matter which forms the major part of OIL SHALE; it is formed by the gradual transformation of sedimented biomolecules in the absence of high temperatures and pressures. (Protokerogen is a less mature form of kerogen from more recent sediments.) Kerogen is believed to be the precursor material of PETROLEUM and natural gas; on heating it yields HYDROCARBONS. (See also MICROBIAL MAT.) kerosene See PETROLEUM. kerosene fungus See HORMOCONIS. kethoxal (2-keto-3-ethoxyl-n-butyraldehyde) A reagent which reacts with and modifies only unpaired guanine residues in DNA or RNA. ketoconazole (1,3-dioxolanylmethylimidazole) An AZOLE ANTIFUNGAL AGENT which is effective against various mucocutaneous and cutaneous mycoses (including those caused by fungi resistant to GRISEOFULVIN) as well as systemic mycoses such as aspergillosis, blastomycosis, coccidioidomycosis, histoplasmosis, etc; unlike most of the imidazole antifungal agents, ketoconazole can be administered orally. ketogenic fermentations Commercial fermentation processes in which polyhydric alcohols are converted to ketoses: see e.g. DIHYDROXYACETONE FERMENTATION and SORBOSE FERMENTATION. a-ketoglutarate dehydrogenase See TCA CYCLE. ketopentose See PENTOSES. kGy See GRAY. Khawkinea See EUGLENOID FLAGELLATES. KIA KLIGLER’S IRON AGAR. Kickxellales An order of fungi (class ZYGOMYCETES) which are typically saprotrophic in soil and dung; all species form one-spored sporangiola – numbers of which are borne on a short hyphal branch (sporocladium). Genera: e.g. Coemansia, Linderina, Martensella (species can be parasitic on other fungi), and Spiromyces. kidney disease (Dee disease) A systemic, usually chronic FISH DISEASE affecting salmonids. The kidneys become pale and swollen with characteristic greyish necrotic lesions; mortality may be high. Pathogen: Renibacterium salmoninarum. 415

kinesis the hyphae. Growth occurs at/below 30° C, but not at 37° C. Type species: K. aurantiaca. kinesis (1) A behavioural response in which the speed (but not the direction) of locomotion of a motile organism depends on the intensity of an external stimulus; e.g., when light intensity increases, an organism may swim faster (positive photokinesis) or slower (negative photokinesis). (See also PHOTOTAXIS.) Kinesis, unlike TAXIS, is a continuous response and is not cancelled by ADAPTATION. (2) A behavioural response in which the rate of activity of an organism depends on the intensity of an external stimulus. When the activity concerned is speed of swimming, the phenomenon is known as orthokinesis (syn. kinesis sense 1). When the activity concerned is frequency of directional change, the phenomenon is termed klinokinesis. [Photochem. Photobiol. (1977) 26 559–560.] kinete A motile zygote, or a motile form derived from a zygote. kinetic response Syn. KINESIS. kinetid (ciliary corpuscle; kinetosomal territory) In ciliates: a unit of the KINETY; it typically includes a CILIUM with its associated kinetosome, KINETODESMA, cytoplasmic membrane and alveolus (see PELLICLE), and may also include e.g. a MUCOCYST, PARASOMAL SAC and TRICHOCYST together with various microfibrils and/or microtubules (e.g. nematodesmata). kinetin 6-Furfurylaminopurine, a compound formed during the hydrolysis of DNA; it has CYTOKININ activity but it apparently does not occur in plants. kinetochore An electron-dense MICROTUBULE-ORGANIZING CENTRE, one of which develops on each side of the CENTROMERE during MITOSIS. kinetochore fibre See MITOSIS. kinetocyst See AXOPODIUM. kinetodesma (kinetodesmos) In some ciliates: one of a series of overlapping endoplasmic fibrils which, by light microscopy, may appear as a single fibre running parallel with, and to the right of, a row of basal bodies in a somatic KINETY; each kinetodesma arises from a kinetosome (near triplets 5–8, GRAIN CONVENTION), passes a little to the right, and then runs anteriorly to terminate in a position where it may overlap the kinetodesma(ta) of the more anterior kinetosome(s). Kinetodesmata have crossstriations of periodicity ca. 30 nm. The role of the kinetodesmata is unknown; they are commonly believed not to be involved in ciliary coordination. (See also RULE OF DESMODEXY; SILVER LINE SYSTEM.) kinetofragments In many members of the KINETOFRAGMINOPHOREA: patches or short rows of kinetids (sometimes with non-ciliferous kinetosomes) in the vicinity of the oral area; their evolutionary origin is presumed to have been the anterior ends of somatic kineties. Kinetofragminophorea A class of protozoa (phylum CILIOPHORA) which characteristically have an apical or subapical cytostome and a CYTOPHARYNGEAL APPARATUS which is usually conspicuous; COMPOUND CILIATURE is typically absent, and ciliature in the oral region is not obviously differentiated from that in other region(s) of the body. STOMATOGENESIS is typically telokinetal (apparently apokinetal in the ENTODINIOMORPHIDA). This class includes many of the ciliates previously referred to as the ‘lower holotrichs’ (e.g. the apostomes, chonotrichs, gymnostomes and trichostomes) together with e.g. the suctorians. Subclasses: GYMNOSTOMATIA, HYPOSTOMATIA, SUCTORIA, VESTIBULIFERIA. kinetoplast In protozoa of the KINETOPLASTIDA: a unique structure which forms a distinct region of the mitochondrion; it

comprises a complex network of numerous catenated circular DNA molecules (kDNA), including several thousand small circles (minicircles) and fewer (ca. 20–50) identical larger circles (maxicircles). The maxicircles are the functional counterpart of the mitochondrial DNA of other eukaryotes, encoding e.g. rRNA and proteins. Minicircles encode most of the gRNAs for RNA EDITING (their only known function). [kDNA: Eukaryotic Cell (2002) 1 495–502]. During cell division, the kinetoplast (and mitochondrion) divides before nuclear division, Kinetoplast division is inhibited by certain drugs, including e.g. ACRIDINES, DIAMIDINES and PHENANTHRIDINE derivatives. (See also DYSKINETOPLASTY.) The kinetoplast stains red with ROMANOWSKY STAINS. Kinetoplastida An order of protozoa (class ZOOMASTIGOPHOREA); each organism has a single nucleus, one or two flagella (which arise from flagellar pockets and which often contain a PARAXIAL ROD) and a single, simple or branched, typically elongated mitochondrion which usually contains a KINETOPLAST located close to the flagellar basal body. (See also GLYCOSOME.) Two suborders: BODONINA and TRYPANOSOMATINA. kinetosomal territory Syn. KINETID. kinetosome (protozool.) Syn. BASAL BODY (b). kinety In ciliates: typically, a longitudinal (‘meridianal’) row of somatic KINETIDS; a kinety corresponds to the ‘primary meridian’ in the SILVER LINE SYSTEM. kingdom A major taxonomic category (see TAXONOMY) ranking above phylum. Organisms are grouped into kingdoms in various ways according to different schemes; e.g., according to the ‘fivekingdoms’ classification scheme the kingdoms are Animalia, FUNGI, MONERA, Plantae, and PROTISTA (sense 2). Kingella A genus of catalase-negative, oxidase-positive bacteria (family NEISSERIACEAE) which occur e.g. in the upper respiratory tract. (See also HACEK.) Cells: rods, 1 × 2–3 µm, in pairs or chains. Growth occurs aerobically, and has been reported to occur anaerobically on blood agar with a gaseous phase of 95% hydrogen and 5% carbon dioxide. The organisms are nutritionally fastidious. Optimal growth temperature: 33–37° C. GC%: ∼47–55. Type species: K. kingae. kinins See CYTOKININS. Kinyoun stain An ACID-FAST STAIN which resembles ZIEHL– NEELSEN’S STAIN but differs in that the stain contains higher concentrations of phenol and basic fuchsin and is used cold; methylene blue may be used as counterstain. [Methods: Book ref. 53, pp. 1381, 1384–1385.] Kirby–Bauer technique See DISC DIFFUSION TEST. kirromycin See POLYENE ANTIBIOTICS (b). kirrothricin See POLYENE ANTIBIOTICS (b). Kirsten murine sarcoma virus (Ki-MSV) A replicationdefective MURINE SARCOMA VIRUS isolated from rats inoculated neonatally with a cell-free extract from thymic lymphomas of C3H mice. Ki-MSV resembles HARVEY MURINE SARCOMA VIRUS in carrying the oncogene v-ras (v-Ki-ras: see RAS) and in causing erythroleukaemia as well as sarcomas in newborn mice. kissing disease See INFECTIOUS MONONUCLEOSIS. Kitasatoa A genus of bacteria which resemble Streptomyces spp in e.g. wall type and phage sensitivity; species have been regarded as members of the genus Streptomyces [JGM (1983) 129 1743–1813] and as species incertae sedis [Book ref. 73, pp. 97–98]. kitazin (O,O-diethyl-S-benzyl phosphorothioate) An ORGANOPHOSPHORUS COMPOUND used as an antifungal agent against rice blast disease; kitazin and its isopropyl analogue (kitazin P) is readily absorbed by plant roots and is rapidly translocated in the 416

Kluyveromyces transpiration stream. It appears to function by inhibiting CHITIN synthesis. klebicin (klebecin, klebocin) See BACTERIOCIN. Klebs–L¨offler bacillus Corynebacterium diphtheriae. Klebsiella (1) A genus of Gram-negative bacteria of the ENTEROBACTERIACEAE (q.v.). Cells: straight rods, ca. 0.3–1.0 × 0.6– 6.0 µm, occurring singly, in pairs, or in short chains; non-motile. The cells are capsulated and usually form convex, glistening, viscid (mucoid) colonies on carbohydrate-rich media. Serotyping [Book ref. 68, pp. 143–164] is based on capsular (K) rather than on O antigens. Some strains may possess mannose-sensitive (type 1) and/or mannose-resistant (type 3) FIMBRIAE. Typical reactions: acid (sometimes with gas) from glucose; H2 S −ve; phenylalanine deaminase −ve; ornithine decarboxylase −ve; myo-inositol +ve; growth in KCN media. Many strains are lactose +ve. GC%: 53–58. Type species: K. pneumoniae. K. oxytoca. Indole +ve; MR −ve; VP +ve; no gas from lactose at 44.5° C; growth occurs at 10° C; melezitose sometimes +ve; pectate +ve. Occurs in the intestines of man and animals and in plant and aquatic environments. K. planticola (= K. trevisanii [IJSB (1986) 36 486–488]). Indole and MR reactions variable; VP +ve; no gas from lactose at 44.5° C; growth occurs at 10° C; melezitose −ve; pectate −ve. Occurs mainly in plant, soil and aquatic environments. K. pneumoniae (including strains sometimes called K. aerogenes and K. edwardsii – cf. AEROBACTER). Indole −ve; no growth at 10° C; melezitose −ve; pectate −ve. Some strains carry out NITROGEN FIXATION. Strains occur in the intestines and respiratory tract of man and animals and may be pathogenic, causing e.g. bovine MASTITIS, equine metritis, OZAENA, PNEUMONIA, and nosocomial URINARY TRACT INFECTION. Subspecies pneumoniae: gas from lactose at 44.5° C; MR −ve, VP +ve (but see METHYL RED TEST); urease +ve. Subspecies ozaenae (formerly K. ozaenae): lactose fermentation variable; MR (usually) +ve; VP −ve; urease variable. Subspecies rhinoscleromatis (formerly K. rhinoscleromatis): lactose −ve; MR +ve; VP −ve; urease −ve. K. terrigena. Indole −ve; no gas from lactose at 44.5° C; growth occurs at 10° C; melezitose +ve; pectate −ve. Occurs mainly in soil and aquatic environments. K. trevisanii. See K. planticola. [Book ref. 22, pp. 461–465.] (2) A genus of EUGLENOID FLAGELLATES found in marine or brackish waters; each cell is partly enclosed in a yellow to brown LORICA. Klebsormidium (Hormidium) A genus of filamentous, unbranched, freshwater or terrestrial green algae (division CHLOROPHYTA). The filaments lack a holdfast and are composed of uninucleate cells each containing a single plate-like chloroplast. Zoospores (rarely formed) are asymmetric, biflagellate and naked, and are released via a pore in the mother cell wall. Sexual reproduction is isogamous; gametes are biflagellate. (cf. STICHOCOCCUS.) Kleinschmidt monolayer technique A method for preparing a nucleic acid for examination by ELECTRON MICROSCOPY. Essentially, a solution of e.g. DNA is mixed with a solution of the globular protein cytochrome c (which adheres to DNA), and one drop of this mixture is allowed to run down a sloping surface onto an air–liquid interface. This gives rise to a monolayer of denatured cytochrome c containing extended molecules of DNA which are thickened by a coating of cytochrome c; dsDNA appears thicker than ssDNA. A small area of the monolayer is transferred to a prepared grid, and the preparation is either shadowed on a rotating platform or stained e.g. with uranyl acetate;

the thread-like molecules of DNA thus become more electrondense than the background. In a modification of this technique, benzalkonium chloride is used instead of cytochrome c; since, in this case, the DNA is not thickened with adherent protein, its relationship to other macromolecules (e.g. polymerases) can be determined more easily. Klenow fragment (Klenow enzyme) The larger of two fragments obtained by proteolytic cleavage (using e.g. subtilisin) of the DNA POLYMERASE I of Escherichia coli. The Klenow fragment retains 5′ -to-3′ polymerase and 3′ -to-5′ exonuclease activities but lacks 5′ -to-3′ exonuclease activity; it has various uses in genetic engineering techniques and in DNA sequencing methods. Klett–Summerson colorimeter See TURBIDIMETRY. Klett unit A unit of turbidity as measured with the Klett–Summerson colorimeter using monochromatic light of a specified colour. Kligler’s iron agar (KIA) A double-sugar–iron agar (cf. TSI AGAR) used e.g. for distinguishing between members of the Enterobacteriaceae. It is prepared as a slope with a deep butt, and consists of nutrient agar (pH 7.4) supplemented with glucose (ca. 0.1%), lactose (1%), sodium thiosulphate (0.05%), ferric ammonium citrate (0.05%), and phenol red (ca. 0.0025%). In general, bacterial reactions with KIA are similar to those with TSI agar; however, the absence of sucrose in KIA means that the lactose-negative reaction given by some organisms is not masked by their ability to attack sucrose. klinokinesis See KINESIS (sense 2). Kloeckera A genus of yeasts (class HYPHOMYCETES) which have teleomorphs in the genus HANSENIASPORA. Vegetative cells are more or less lemon-shaped (apiculate) and reproduce by bipolar budding in basipetal succession; pseudomycelium may be formed. All species ferment glucose; some ferment sucrose, none ferments maltose (although some species can assimilate maltose). NO3 − is not assimilated. All species require inositol and pantothenate for growth. Species (K. africana, K. apiculata, K. apis, K. corticis, K. japonica, K. javanica) have been isolated from fruit, soil, bark etc. [Book ref. 100, pp. 873–881.] Klonostricha See HYPOTRICHIDA. Klossiella See ADELEORINA. Kluyver effect The phenomenon in which certain yeasts can utilize particular disaccharides aerobically, but not anaerobically. The mechanism underlying the effect is unknown [JGM (1982) 128 2303–2312]. Kluyvera A genus of motile bacteria of the ENTEROBACTERIACEAE. MR +ve; VP −ve; usually indole +ve and citrate +ve. 2-Oxoglutarate is formed from glucose. The organisms occur in food, soil and sewage, and may be opportunist pathogens in man. [Book ref. 22, pp. 511–513.] Kluyveromyces A genus of yeasts (family SACCHAROMYCETACEAE) in which the cells are spheroidal, ovoid, ellipsoidal, or cylindrical to elongate; vegetative reproduction occurs by multilateral budding. Pseudomycelium may be formed. Asci are evanescent; they contain one to many spores which may be crescent-shaped, reniform, spheroidal etc, and which tend to agglutinate after liberation. Cells contain ubiquinone-6 (Q6). All species can ferment glucose; K. marxianus var. lactis and some strains of K. marxianus var. marxianus can ferment LACTOSE. NO3 − is not assimilated. Eleven species have been recognized primarily on the basis of hybridization data; on this basis some former species (e.g. K. bulgaricus, K. fragilis, K. lactis) have been relegated to varieties of K. marxianus – e.g., ‘K. fragilis’ is K. marxianus var. marxianus (anamorph: Candida kefyr, = ‘C. pseudotropicalis’), and 417

k-MTs field diaphragm. (v) Focus on the specimen with a low-power (e.g. ×10) objective, and adjust the substage condenser slightly so that the edge of the field diaphragm is in sharp focus in the plane of the specimen. (vi) Open the field diaphragm until the small disc of light in the centre of the field of view has expanded to cover the entire field. Under these conditions an image of the lamp’s filament is formed in the lower focal plane of the substage condenser, and divergent rays from each point of the filament’s image pass through the condenser and emerge as parallel rays which illuminate the specimen. koji A preparation consisting of mould (usually Aspergillus oryzae) growing on cooked cereal and/or soybeans; the mould produces enzymes (including a range of proteases, amylases, pectinases, glutaminase, etc) and is used in the production of e.g. SOY SAUCE and MISO. The inoculum for making koji is a koji starter or tane koji : a powder consisting of mould spores. Tane koji is typically made by inoculating steamed polished rice with spores of selected fungal strains; the rice is spread in shallow trays, incubated at 30° C for ca. 5 days, and the spores are then harvested and dried. kojibiose A reducing disaccharide: a-D-glucopyranosyl-(1 → 2)D-glucopyranose. It can occur e.g. as a product of enzymic degradation of certain plant carbohydrates, and is present in glycerol TEICHOIC ACIDS of group D streptococci (in which it is linked to the C-2 position of glycerol and may be esterified with D-alanine). kojic acid (5-hydroxy-2-hydroxymethyl-4-pyrone) A secondary metabolite produced e.g. by Aspergillus spp (particularly the flavus–oryzae group) when grown on glucose, xylose or certain other sugars. It is a chelating agent which gives a strong blood-red colour with Fe3+ ; it also has weak antibiotic activity (enhanced by certain metal ions), being effective mainly against Gram-negative bacteria. Kolmer CFT See STANDARD TESTS FOR SYPHILIS. Kolpoda Syn. COLPODA. kombu See LAMINARIA. Konservomat See BATCH RETORT. Kopeloff modification A modification of the GRAM STAIN used for staining anaerobic bacteria. The technique involves the addition of ca. 5 drops of NaHCO3 solution (5%) to the smear after the latter has been flooded with crystal violet (1%); the iodine solution (iodine 2%, KI 0.1%) includes NaOH (0.4%), decolorization is carried out with acetone–alcohol, and safranin (2%) is used for counterstaining. Koplik’s spots Small, white, necrotic lesions formed in the mouth in the early stage of MEASLES. Kordyana See EXOBASIDIALES. Korean haemorrhagic fever (epidemic haemorrhagic fever) A VIRAL HAEMORRHAGIC FEVER involving renal dysfunction, proteinuria and oliguria; the mortality rate may be up to 30%. The causal agent is the Hantaan virus (see HANTAVIRUS); reservoirs of infection are found in rodent populations. Infection typically occurs by inhalation of aerosols of urine, faeces etc. from infected rodents. The disease occurs in Asia and Europe. Korfia See HELOTIALES. Kornberg enzyme See DNA POLYMERASES. Koserella A genus of Gram-negative bacteria of the ENTEROBACTERIACEAE. K. trabulsii (formerly known as ‘enteric group 45’ and originally identified as an atypical strain of Hafnia alvei ) has been isolated from clinical specimens; it is MR +ve; VP −ve; indole −ve; citrate +ve; H2 S − ve; urease −ve; LDC

‘K. lactis’ is K. marxianus var. lactis (anamorph: Candida sphaerica). Other species include e.g. K. aestuarii, K. africanus, K. blattae, K. polysporus, K. thermotolerans (anamorph: Candida dattila). [Book ref. 100, pp. 224–251.] Kluyveromyces spp occur in a wide range of habitats: e.g. sea-water (K. aestuarii ), soil, insects, fruit and other plant material, foods and beverages, etc. (See also CHEESE-MAKING (c), SINGLE-CELL PROTEIN, YEAST EXTRACT, and KILLER PLASMIDS.) k-MTs MICROTUBULES attached to a KINETOCHORE. knallgas bacteria Syn. HYDROGEN-OXIDIZING BACTERIA. knallgas reaction (oxyhydrogen reaction) The oxidation of gaseous hydrogen by oxygen. In the HYDROGEN-OXIDIZING BACTERIA this reaction, which provides energy for growth, involves one or more types of HYDROGENASE and a respiratory chain which may contain e.g. a-, b-, c- and o-type cytochromes, iron–sulphur proteins and ubiquinones. [Ubiquinones in hydrogen-oxidizing bacteria: SAAM (1983) 4 181–183.] In e.g. chemolithoautotrophically grown Paracoccus denitrificans, electrons from hydrogen appear to be transferred to oxygen via hydrogenase, UQ-10 and cytochromes b562 and o. In e.g. ‘Alcaligenes eutrophus’ (which has both NAD-independent and NAD-reducing hydrogenases) it has been suggested that electrons from hydrogen may be donated to the respiratory chain and/or to NAD – the NADH being oxidized via the respiratory chain. knockout mice Mice in which specific gene(s) have been disrupted (by genetic manipulation at the embryo stage) such that the corresponding gene product(s) are not synthesized in active form. knopvelsiekte The severe form of LUMPY SKIN DISEASE. knot (in DNA) An entanglement within a single, circularly closed DNA molecule, resolution of which (to form a knotfree cccDNA molecule) requires the activity of a TOPOISOMERASE (q.v.). koala (chlamydiosis in) See CHLAMYDIA. Koch–Weeks bacillus Haemophilus aegyptius. Koch’s blue bodies See EAST COAST FEVER. Koch’s phenomenon The phenomenon in which different responses are given by healthy and tuberculous guinea pigs to a subcutaneous injection of virulent tubercle bacilli; reactions in the tuberculous animals are manifestations of DELAYED HYPERSENSITIVITY (q.v.). Koch’s postulates According to Robert Koch (1843–1910): a set of conditions which should be fulfilled in order to establish that a given organism is the causal agent of a particular disease. (i) The organism must be present in every case of the disease. (ii) It should be isolable in pure culture. (iii) Inoculation of susceptible animals with the isolated organism must produce the disease. (iv) The organism must be observable in, and/or isolable from, the (experimental) diseased animals. ¨ Koehler illumination Syn. KOHLER ILLUMINATION. Kofoidinium A genus of DINOFLAGELLATES. K¨ohler illumination (Koehler illumination) In MICROSCOPY: illumination in which the entire field is lit with uniform intensity, regardless of any non-uniformity in the light source (cf. CRITICAL ILLUMINATION). To obtain K¨ ohler illumination with an external lamp having a condensing lens with an iris diaphragm (field diaphragm) outside it: (i) Close the substage CONDENSER diaphragm (aperture diaphragm). (ii) Open the field diaphragm. (iii) Using the microscope’s plane mirror, image the lamp’s filament on the underside of the aperture diaphragm; thereafter, keep lamp and microscope in the same relative positions. (iv) Open the aperture diaphragm and almost close the 418

Kyzylagach virus Kupffer cells Actively phagocytic cells which line the liver sinusoids. Kurthia A genus of Gram-positive, asporogenous, catalasepositive, obligately aerobic bacteria which occur e.g. in meat and meat products. In the exponential growth phase the organisms occur in long chains of rods (or of short filaments) but in the stationary phase coccoid forms or short rods predominate; individual rods are peritrichously flagellated. Kurthia spp are chemoorganotrophs which can utilize certain alcohols (e.g. ethanol, ethanediol), amino acids (e.g. L-alanine) and fatty acids (e.g. butyric acid). VP −ve. Indole-negative. The type species, K. zopfii, grows in the temperature range 5–35° C and is killed by heating to 55° C/20 minutes. K. gibsonii grows in the range 5–45° C and survives heating to 55° C/20 minutes [SAAM (1983) 4 253–276]. GC%: ca. 36–38. kuru A human TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY [early description: NEJM (1957) 257 974–978]. The incubation period may range from a few years to some 30 years or more; characteristically there is ataxia, tremor, dysarthria and sometimes late dementia, and death occurs within a year of the onset of symptoms. Kuru is found in certain regions of Papua New Guinea and is believed to result from the ingestion of prion-containing flesh during ritual cannibalism; as this practice has declined, the incidence of kuru has decreased. Kuru can be transmitted experimentally to chimpanzees and to other primate and non-primate animals; goats (but not sheep) inoculated with tissue from kuru victims develop a disease that closely resembles SCRAPIE. [Review of kuru: Book ref. 159, pp. 483–544 (497–510).] Kusnezovia A genus of poorly-characterized, manganesedepositing bacteria found in mud; the organisms have not been obtained in pure culture, and the validity of the genus (and of an apparently similar genus, Caulococcus) has been questioned [Book ref. 45, pp. 529–530]. Kyasanur Forest disease An acute, tick-borne human disease (vector: mainly Haemaphysalis sp) caused by a flavivirus (see FLAVIVIRIDAE); it occurs in Mysore State, India. Onset is sudden, with e.g. fever, headache, severe myalgia, haemorrhages, etc. Mortality rates are generally low (95%). The disease may also affect certain other ungulates (e.g. sheep, wildebeest, deer). [Review of the disease: VR (1984) 114 581–583.] malignant oedema (vet.) Tissue oedema and necrosis, often involving frank GAS GANGRENE, due to wound infection by one or more species of Clostridium – e.g. C. chauvoei, C. novyi, C. septicum, C. sordellii. Symptoms: fever, with a soft, red, local swelling which becomes dark; in some cases gas production gives rise to a frothy exudate from the wound. Death usually occurs within 1–2 days. Treatment: parenteral administration of antibiotics, antitoxin therapy (appropriate only in early stages of the disease), irrigation of the wound with hydrogen peroxide. (See also SWELLED HEAD.) malignant pustule Cutaneous ANTHRAX. malignant tertian malaria See MALARIA. mallein test (vet.) A test for GLANDERS (sense 1) involving the intradermal injection of mallein (containing antigens of the pathogen) e.g. into the lower eyelid; a positive reaction is GONIST;

457

Mancini test Mancini test See SINGLE DIFFUSION. mancozeb An agricultural antifungal agent consisting of a complex of zinc and MANEB; it is used, for example, against late blight of potato. Mandelamine See HEXAMINE. mandelic acid Hydroxyphenylacetic acid: C6 H5 .CHOH.COOH. Mandelic acid has bacteriostatic properties and is used as a urinary antiseptic – being excreted unchanged if the urine is sufficiently acidic; it may be used in combination with HEXAMINE. Mandler filter See FILTRATION. maneb (dithane M-22) Manganese ethylene-BISDITHIOCARBAMATE, an agricultural antifungal agent with a spectrum of activity similar to that of ZINEB; it is used e.g. to control diseases caused by Alternaria solani and Phytophthora infestans. manganese (in microbiology) See e.g. IRON BACTERIA, PSEUDOCATALASE and SUPEROXIDE DISMUTASE. mango black spot See BLACK SPOT (3). mannans Polysaccharides composed of manosyl residues. Linear (1 ! 4)-b-linked mannans occur in some algae of the Chlorophyta (e.g. Acetabularia, Codium) – in which they may replace cellulose as the main structural component of the CELL WALL – and in certain plants (e.g. in many palm seeds); in many yeasts the CELL WALL has a high mannan content. Heteroglycans consisting of (1 ! 4)-b-linked D-glucosyl and D-mannosyl residues (glucomannans) are major HEMICELLULOSES in gymnosperms. mannitol The POLYOL corresponding to mannose; it occurs e.g. in many plants, algae, fungi and lichens, and is formed by the reduction of fructose by certain bacteria (see e.g. SILAGE). Mannitol is a major carbohydrate in members of the Phaeophyta and in chrysophytes (in which it is the primary photosynthetic carbohydrate) and in ascomycetous and basidiomycetous fungi; earlier reports that it occurs in the Rhodophyta appear to be incorrect [Book ref. 37, pp. 162–165]. Mannitol can have an osmoregulatory role in certain algae and fungi exposed to fluctuating salinities. mannopine An opine of the agropine type: see e.g. HAIRY ROOT. mannose An aldohexose found e.g. in MANNANS and in animal mucolipids and mucoproteins. (See also NEURAMINIC ACIDS; cf. MANNITOL.) mannose-binding lectin See COMPLEMENT FIXATION (c). mannose-resistant haemagglutination See FIMBRIAE. mannose-sensitive haemagglutination See FIMBRIAE. mantle (mycol.) See MYCORRHIZA. Mantonella See EIMERIORINA. Mantoniella See MICROMONADOPHYCEAE. Mantoux test See TUBERCULIN TEST. manure gas poisoning Poisoning of man or animals by gases (e.g. H2 S, NH3 , CO2 ) produced by anaerobic bacteria in manure stored in large slurry pits; exposure to high concentrations of these gases – e.g. during mixing of slurries prior to emptying pits – can be rapidly fatal. MAP (1) (M-associated protein) A protein often associated with the streptococcal M PROTEIN; it also occurs in streptococci of groups C and G that have M-like antigens. (2) MICROTUBULE-ASSOCIATED PROTEIN. (3) METHIONINE AMINOPEPTIDASE. MAP kinase See ANTHRAX TOXIN. map lichens Rhizocarpon spp, particularly R. geographicum. map unit (map distance) (1) Syn. CENTIMORGAN. (2) Any unit used for indicating the position of markers in a genome: e.g. the chromosome of Escherichia coli is divided into 100 minutes (see INTERRUPTED MATING).

maple bark strippers’ disease An EXTRINSIC ALLERGIC ALVEOLITIS associated with inhalation of the spores of Cryptostroma corticale. Maranil Dodecylbenzolsulphonate: an agent used e.g. in BTB AGAR (0.005%) to inhibit swarming by Proteus spp. Marasmius See AGARICALES (Tricholomataceae); see also MYCORRHIZA. marble bone Syn. OSTEOPETROSIS. marble spleen disease A disease of pheasants caused by an adenovirus very similar to the causal agent of HAEMORRHAGIC ENTERITIS OF TURKEYS. The disease is acute and rapidly fatal, and involves severe pulmonary oedema with enlargement and mottling of the spleen. [Book ref. 116, pp. 537–539.] Marburg fever (green monkey fever) A VIRAL HAEMORRHAGIC FEVER, caused by the Marburg virus (see FILOVIRIDAE), first reported in 1967 when an outbreak occurred in Marburg (W. Germany) among laboratory personnel working with infected tissues of the African green monkey (Cercopithecus aethiops). Incubation period: ca. 6–10 days. Onset is sudden, with e.g. fever, mental confusion, diarrhoea, haemorrhages from mucous membranes, and often a maculopapular rash. The disease is often fatal. (Ebola virus causes a similar disease.) Marburg virus See FILOVIRIDAE. Marek’s disease (fowl paralysis) A POULTRY DISEASE caused by gallid herpesvirus 1 (see GAMMAHERPESVIRINAE); chickens, turkeys, pheasants, ducks, pigeons and other birds are susceptible, but the principal natural hosts appear to be domestic chickens and their close relatives (Gallus spp). Infection seems to occur primarily by inhalation of ‘feather dust’ released from the feather follicles of infected birds. The classical (chronic) form of the disease involves the development of T-cell lymphomas in the peripheral nerves, causing progressive paralysis. A visceral (acute) form also occurs in which lymphomas develop in internal organs; mortality rates for the acute disease are commonly high. Infected birds remain carriers – probably for life. Live vaccines are available: e.g., vaccination with gallid herpesvirus 2 (‘turkey herpesvirus’) protects chickens and turkeys against Marek’s disease. [Review of Marek’s disease and its virus: Book ref. 105, pp. 155–183.] Marek’s disease virus can also cause chronic atherosclerosis in SPF chickens [AJP (1986) 122 62–70]; MDV infection apparently prevents activation of cytoplasmic cholesteryl esterase in arterial smooth muscle cells [JBC (1986) 261 7611–7614]. These observations lend support to the hypothesis that herpesvirus infection may play a role in the pathogenesis of atherosclerosis (‘hardening of the arteries’) in man [review: MS (1986) 3 50–52]. Marfanil (sulphamylon; p-aminomethylbenzenesulphonamide: NH2 CH2 .C6 H4 .SO2 .NH2 ) A drug which has been used e.g. in the topical treatment of wounds, burns, etc. It differs from other SULPHONAMIDES in that it is not a sulphanilamide derivative, the p-aminomethyl group replacing the p-amino group of sulphanilamide. marginal zone B cells (MZ B cells) A subset of B LYMPHOCYTES found within the marginal zone of the spleen (i.e. the junction of red and white pulp) – together with DENDRITIC CELLS and macrophages; cells in the marginal zone are considered to represent an early form of defence against blood-borne pathogens. MZ B cells are important in responses to T-independent antigens, and they are particularly sensitive to lipopolysaccharides. [See e.g. Science (2000) 290 89–92.] Marinomonas See ALTEROMONAS. 458

Mastadenovirus marker (genetics) A genetic locus which is associated with a particular (usually readily detectable) phenotypic characteristic: e.g., an antibiotic resistance gene. marker rescue Conferment on a gene, or genes, of the ability to replicate as a result of the integration of the gene(s) with a replicon. (See also REACTIVATION sense 1.) Marseilles fever Syn. BOUTONNEUSE. marsh gas See ANAEROBIC DIGESTION. Marssonina See MELANCONIALES. marsupium Syn. BROOD POUCH. Marteilia See STELLATOSPOREA. Martensella See KICKXELLALES. marticin See NAPHTHAZARINS. Mason–Pfizer monkey virus (MPMV) An exogenous, xenotropic retrovirus of the TYPE D RETROVIRUS GROUP. MPMV was isolated from a carcinoma of a rhesus monkey; it has not been shown to be oncogenic either in its natural host or in other primates. (cf. SIMIAN AIDS.) MASP MBL-associated serine protease: see COMPLEMENT FIXATION (c). mast cell A cell which can respond to certain stimuli by rapidly secreting e.g. vasoactive products; it is important e.g. in immediate-type hypersensitivity reactions and in acute INFLAMMATION. Unlike the BASOPHIL, the mast cell is primarily a noncirculating cell, occurring e.g. in blood vessels and in the lymphatic system. The (basophilic) cytoplasmic granules in the mast cell contain a variety of biologically active products – e.g. HISTAMINE, HEPARIN, SEROTONIN (significant amounts in some species), and proteases – which are released, within 15–20 sec, on activation and degranulation of the cell. Mast cells can be activated and degranulated e.g. by certain CYTOKINES, ANAPHYLATOXINS, IgE (and certain IgG) antibodies together with their homologous antigens, IgE aggregates (not monomeric IgE), bivalent anti-IgE receptor antibodies, and some LECTINS (e.g. PHA). The mast cell surface contains many high-affinity receptor sites for the Fc portion of IgE, and the cross-linking of surfacebound IgE antibodies by antigen (allergen) appears to be a trigger for degranulation (see also TYPE I REACTION). (Degranulated mast cells gradually replace their histamine.) Activated mast cells also produce e.g. SUPEROXIDE, H2 O2 , and factors which are chemotactic for NEUTROPHILS and EOSINOPHILS. Mastadenovirus (mammalian adenoviruses) A genus of adenoviruses (family ADENOVIRIDAE) which infect mammals (including man); type species: human adenovirus type 2 (D h2, D Ad2). Almost all mammalian adenoviruses share a common (groupspecific) antigen (a hexon surface antigen); subgenus-specific and species-specific antigens can also be detected. Human adenovirus species are designated by the prefix Ad (or h) followed by the species (serotype) number: Ad1, Ad2, etc (or h1, h2, etc). Human adenoviruses can cause a wide range of diseases (as well as subclinical infections) in humans. Several can induce tumours (mainly sarcomas) when injected into newborn rodents, but none is known to cause tumours in man under natural conditions; however, most human adenoviruses can cause morphological transformation in certain types of cell cultures, causing the formation of characteristic foci of small, often polygonal cells containing scanty cytoplasm and capable of dividing indefinitely. Transformation of cells by adenoviruses involves the integration of viral DNA sequences into host chromosomal DNA. Depending on the host cell, the whole viral genome or (more commonly) a fragment of it may be integrated; integration apparently occurs at random sites in the host DNA, and the viral DNA – together with flanking

host sequences – often undergoes amplification. Transformation requires the integration of at least the E1a region, but the mechanism of transformation is unknown. [Adenoviral genes and transformation: Book ref. 110, pp. 125–172.] Human adenoviruses have been classified into subgenera (subgroups) on the basis of e.g. DNA characteristics, oncogenicity, subgenus-specific antigens, morphology, haemagglutinating properties, etc: Subgenus A (Ad12, 18 and 31): GC% of the DNA: 47–49; length of virion fibres: 28–31 nm. Viruses in this subgenus are highly oncogenic when injected into newborn hamsters or rats, causing tumours after ca. 2–4 months; in man, they are associated with upper respiratory tract infections and diarrhoea, or infection may be subclinical. Subgenus B (Ad3, 7, 11, 14, 16, 21, 34 and 35): GC% of the DNA: 49–52; length of the virion fibres: 9–11 nm. Viruses in this subgenus are weakly oncogenic when injected into newborn hamsters, causing tumours at low incidence after ca. one year; in man, they cause e.g. ARD (Ad3, 7, 14, 21), acute haemorrhagic CYSTITIS (Ad11), PHARYNGOCONJUNCTIVAL FEVER, pneumonia, etc. Subgenus C (Ad1, 2, 5 and 6): GC% of the DNA: 57–59; length of the virion fibres: 23–31 nm. These viruses are nononcogenic in newborn rodents, but can cause transformation of rodent cells in vitro; they can cause mild to severe upper respiratory tract disease in young children. Subgenus D (Ad8–10, 13, 15, 17, 19, 20, 22–30, 32, 33, 36, 37–39): GC% of the DNA: 57–60; length of the virion fibres: 12–13 nm. The viruses are non-oncogenic in newborn hamsters, but may cause mammary adenomas in newborn female rats and can transform rodent cells in vitro. Ad8 and Ad19 are causal agents of EPIDEMIC KERATOCONJUNCTIVITIS. Subgenus E (Ad4): GC% of the DNA: 57; length of virion fibres: 17 nm. Non-oncogenic in newborn hamsters. Ad4 can cause EPIDEMIC KERATOCONJUNCTIVITIS, acute respiratory disease (see ARD), and PHARYNGOCONJUNCTIVAL FEVER. Two further subgenera, F (Ad40) and G (Ad41), have been recognized but are not yet well characterized; these include the ‘enteric’ or ‘fastidious’ adenoviruses [review: Arch. Virol. (1986) 88 1–17] which cause diarrhoea in infants and young children, and which cannot be propagated in conventional cell cultures. They can be grown in an Ad5-transformed human embryonic kidney cell line. Most human adenoviruses will not replicate readily in simian cell lines, but may do so in the presence of simian virus 40 (SV40); SV40 can interact extensively with human adenoviruses, e.g. forming SV40–adenovirus hybrids [Book ref. 116, pp. 399–449]. Animal adenovirus nomenclature follows at least two different conventions; a species may be designated by a three-letter prefix derived either from the name of the animal plus ‘AV’ (e.g. BAV for bovine adenovirus, SAV for simian adenovirus [Book ref. 116, p. 500]) or from the genus name of the host animal (e.g. bos for cattle, sus for pigs, equ for horses, mus for mice [Book ref. 23, p. 60]), followed in either case by the serotype (species) number – e.g. BAV-3 or bos-3, MAV-1 or mus-1, etc. Infection of animals by adenoviruses may result in (usually mild) respiratory or diarrhoeal illnesses, conjunctivitis, etc. Canine adenovirus type 1 (CAV-1, can-1) can cause encephalitis in foxes and e.g. hepatitis in dogs; CAV-2 is thought to be a causal agent of laryngotracheitis (‘kennel cough’) in dogs. Several animal adenoviruses (11 simian, 2 bovine and 2 canine species) can induce tumours when injected into newborn hamsters. [Animal adenoviruses: Book ref. 116, pp. 497–562.] 459

Mastigocladus maternal inheritance A form of CYTOPLASMIC INHERITANCE in which certain characteristics are transmitted to sexually derived progeny only from the female parent cell. Various hypotheses have been proposed to account for maternal inheritance, and different mechanisms may be applicable in different cases. Thus, in certain cases where maternally inherited genes occur in mitochondria, mitochondria from the male parent are presumed to be excluded from the zygote (see e.g. POKY MUTANT). To account for the maternal inheritance of genes in chloroplast DNA (a phenomenon recorded in some isogamous green algae) it has been proposed that chloroplast DNA from the male parent is preferentially digested [MS (1985) 2 267–270]. mating Syn. CONJUGATION (sense 1). mating type A strain of an organism which can interact sexually only with other, genetically distinct, strains of the same species. (See also HETEROTHALLISM and SYNGEN.) In Saccharomyces cerevisiae mating type is determined at a single genetic locus, designated MAT, on chromosome III. In haploid cells, MAT is occupied by either the MAT a allele or the MAT a allele – which occur in a and a mating types respectively. According to the widely-accepted ‘a1-a2 hypothesis’, MAT a and MAT a regulate the same groups of structural genes, but their different modes of regulation result in the development of phenotypically different mating types; thus, groups of genes known as ‘a-specific genes’ and ‘a-specific genes’ (which specify the a and a phenotypes, respectively) occur in the cells of both a and a mating types, and the way in which these genes are controlled by the MAT locus determines the cell’s mating type. MAT a is transcribed in two parts from a central promoter region, the two RNA transcripts being copied from different DNA strands; the parts are called MAT a1 and MAT a2. MAT a1 expression is necessary for the transcription of the a-specific genes – whose products include the a-f actor (a PHEROMONE). MAT a2 is a negative regulator of a-specific genes. The (single) MATa product has no effect in the a-type haploid vegetative cell; by default, a-type genes (including that encoding the a-type pheromone a-factor) are expressed in cells of this mating type. In most natural isolates of S. cerevisiae, spontaneous conversion of the MAT a allele to the MAT a allele, and vice versa, occurs quite frequently – with concomitant switching of mating type; a given population will therefore consist of a mixture of compatible mating types (a and a) and will give the appearance of being homothallic. (Stability at the MAT locus involves another locus, designated HO for homothallism, located on chromosome IV.) Switching involves a cassette mechanism, unexpressed copies of MATa and MATa being stored on chromosome III at sites designated, respectively, HMR and HML; these genes are silenced by the transcription-resistant form of their chromatin. Switching requires a double-stranded cut at the MAT locus, made by the HO (‘YZ’) endonuclease, followed by excision of the resident MAT allele and its replacement with a copy of the allele of the other mating-type (gene conversion). When a-type and a-type cells are mixed, the pheromone from a given mating type causes cells of the other type to stop in the G1 phase of the CELL CYCLE, and to exhibit a mating typespecific glycoprotein component of the cell wall which promotes fusion between cells of opposite mating types. The zygote, which lacks mating potential and mating type characteristics, is designated a/a. In the a/a zygote, the a2 and a1 proteins jointly switch off various genes, including a-specific and a-specific genes and the ‘haploid-specific’ genes active in both mating types.

Mastigocladus See FISCHERELLA and CHLOROGLOEOPSIS. Mastigomycota In some taxonomic schemes: a division equivalent to the subdivision MASTIGOMYCOTINA. Mastigomycotina A subdivision of unicellular and (more commonly) mycelial fungi (division EUMYCOTA); most species (though not e.g. Peronospora spp) form flagellated spores or gametes. Classes: CHYTRIDIOMYCETES, HYPHOCHYTRIOMYCETES, OOMYCETES. mastigoneme See FLAGELLUM (b). Mastigophora A subphylum of protozoa (phylum SARCOMASTIGOPHORA) which have one or more flagella; cell division is typically symmetrogenic. Classes: PHYTOMASTIGOPHOREA and ZOOMASTIGOPHOREA. mastigosome Syn. BASAL BODY (b). mastitis Inflammation of the mammary gland; it may or may not be of microbial causation. (a) (med.) Puerperal mastitis may occur in lactating women, commonly ca. 1 month after childbirth, and may be caused by staphylococci or streptococci. (b) (vet.) Mastitis is quite common among farm animals, but is uncommon in mares. In cows, common causal agents include e.g. Actinomyces pyogenes (‘summer mastitis’ in dry cows and precalving heifers), Escherichia coli (‘coliform mastitis’ is caused by E. coli or other coliforms), Staphylococcus aureus (see also BLACK POX), and Streptococcus agalactiae, but any of a wide range of organisms may be involved, including various other bacteria (e.g. species of Pasteurella, Pseudomonas), fungi (e.g. Aspergillus, Candida) and algae (Prototheca spp). In ewes, mastitis is commonly caused by E. coli, S. aureus or S. agalactiae but may be due e.g. to Mycoplasma agalactiae, while in mares the causal agent may be e.g. Streptococcus equi. In cows, predisposing factors include age and the stage of lactation; thus, e.g. cows which have had ca. four or more lactations, and those within the first two months of lactation, are more susceptible than others. Symptoms may range from mild to an acute inflammatory condition with fever and other systemic effects; the milk contains an increased number of white blood cells, and may contain a significant number of pathogenic microorganisms. (See also CALIFORNIA MASTITIS TEST and CAMP TEST.) Treatment: e.g. parenteral administration or intramammary infusion of antibiotics [Book ref. 33, pp. 451–500]. [Chemoprophylaxis in bovine mastitis: Book ref. 121, pp. 193–204.] [DNA fingerprinting and ribotyping in epidemiological investigations of outbreaks of Pseudomonas aeruginosa mastitis among Irish dairy herds: AEM (1999) 65 2723–2729.] mat (microbial) See MICROBIAL MAT. MAT locus See MATING TYPE. matching (in taxometrics) See entry SSM . MATE Multidrug and toxic compound extrusion: an EFFLUX MECHANISM which e.g. mediates resistance to antibiotic(s) in certain bacteria (including e.g. Escherichia coli and Vibrio parahaemolyticus). [Mol. Microbiol. (1999) 31 393–395.] mate killer The term for certain (endosymbiont-containing) strains of ciliate protozoa which, on conjugation (mating), cause the death of the conjugal partner; mate killers include strains of Paramecium aurelia (endosymbiont: Caedibacter paraconjugatus or Pseudocaedibacter conjugatus) and of Euplotes crassus and E. patella (endosymbionts unnamed). In each case mating is essential for killing; thus, e.g. the ingestion of C. paraconjugatus by sensitive paramecia does not cause harmful effects. maternal immunity PASSIVE IMMUNITY acquired by a fetus or neonate from its mother either via the placenta or from COLOSTRUM. 460

measles between an ecotropic MuLV and an endogenous xenotropic retrovirus. Since many MCF viruses have a leukaemogenic potential greater than that of the parent MuLV, it has been suggested that an MCF component may be responsible for ‘MuLV-induced’ leukaemogenesis. (See also AKV; cf. FRIEND VIRUS.) McFadyean’s test A confirmatory test for ANTHRAX carried out, post-mortem, on an infected guinea pig. Blood (from the heart), or a spleen imprint, is stained with polychrome methylene blue; in a positive test, the stained smear reveals large, blue, squareended bacilli surrounded by a reddish granular capsule. McIntosh and Fildes’ anaerobic jar (modified) An ANAEROBIC JAR which consists of a strong cylindrical metal chamber with a flat, circular, gas-tight lid; such jars are referred to by various trade names (e.g. Torbal jar). Media etc are placed in the jar, and the lid is secured by means of a screw clamp. The jar is then evacuated, by a suction pump, via one of two screw-controlled needle valves in the lid; this valve is then closed. (To prevent the vacuum sucking the agar from Petri dishes, plates are incubated lid-side up – cf. GASPAK.) The jar is filled, via the other valve, with gas(es) – e.g. H2 , or CO2 and H2 – from a compressed-gas cylinder or from a gas-filled rubber bladder; this valve is closed, and the cycle of evacuation and re-filling is carried out several times. Attached to the inside of the lid is a gauze envelope containing a catalyst (e.g. palladium-coated pellets of alumina) which promotes chemical combination between hydrogen and the last traces of oxygen in the jar; such catalysts work at room temperatures and are called ‘cold’ catalysts. The jar also has a side-arm to which is attached a small, thick-walled, closed glass vessel which communicates with the interior of the jar and which contains an indicator of anaerobiosis (e.g. METHYLENE BLUE solution). MCP (1) Methyl-accepting chemotaxis protein (see CHEMOTAXIS). (2) Membrane co-factor protein (see COMPLEMENT FIXATION (b).) MCS (multiple cloning site) See POLYLINKER. M-CSF See COLONY-STIMULATING FACTORS. MDa Megadalton: 106 DALTONS. MDCK cells Madin–Darby canine kidney cells: a heteroploid cell line derived from the kidney of an apparently normal dog. MDCK cell cultures have been used e.g. for the primary isolation and passage of influenzavirus type A [PNAS (2000) 97 9654–9658]. MDP Muramyl dipeptide: N-acetylmuramyl-L-alanyl-D-isoglutamine; a water-soluble component of a modified form of complete FREUND’S ADJUVANT. mean doubling time See GROWTH (a). mean generation time See GROWTH (a). measles (morbilli; cf. RUBEOLA) An acute and highly infectious human disease which affects mainly children. (Other primates can be affected.) The causal agent is a MORBILLIVIRUS. Transmission occurs by droplet infection or via fomites; the conjunctivae may be important sites of infection. Incubation period: 8–12 days. In the prodromal stage (2–4 days) there is coryza, cough, fever, and the appearance of KOPLIK’S SPOTS. Subsequently, a maculopapular rash develops on the head, then on the limbs and trunk. The spots are initially bright pink but become deeper red and then brownish – a phenomenon known as ‘staining’. Viruses are present in the urine, nasopharyngeal secretions etc during the prodromal period and for several days after the appearance of the rash. Complications may include ENCEPHALITIS [NEJM (1984) 310 137–141]; secondary bacterial infection may result in e.g.

matrix protein (bacteriol.) A former term for PORIN. maturase See SPLIT GENE (b) and (c). Maurer’s clefts (Maurer’s dots) Large dots, streaks, or ‘commas’ sometimes observed, on suitable staining, in erythrocytes infected with certain stages of Plasmodium falciparum. Maus Elberfeld virus See CARDIOVIRUS. maxicell A bacterial ‘cell’ obtained by UV irradiation of recA, uvrA mutant strains of e.g. Escherichia coli. Irradiation of such mutants results in damage to and degradation of chromosomal DNA (cf. RECKLESS DNA DEGRADATION); however, if small, multicopy plasmids are present in such cells, some of the plasmids may be undamaged by the UV radiation and can subsequently replicate. These cells therefore synthesize plasmidencoded proteins almost exclusively; the proteins can be labelled by adding e.g. [35 S]methionine to the medium. [JB (1979) 137 692–693.] (cf. MINICELL.) maxicircle DNA See KINETOPLAST. maximum specific growth rate (µmax ) See SPECIFIC GROWTH RATE. Mayaro fever An epidemic febrile human disease caused by an ALPHAVIRUS and transmitted by mosquitoes (e.g. Haemagogus janthinomys); it occurs in the Caribbean and parts of S. America. Symptoms: e.g. headache, myalgia, arthralgia, and a maculopapular rash. Monkeys are probably the main natural hosts. Mayorella A large genus of amoebae (order AMOEBIDA) which characteristically form several bluntly conical, hyaline pseudopodia of similar lengths. (See also UROID.) Some species have a surface covering of complex scales (not discernible by light microscopy). Species occur in freshwater habitats and e.g. sewage treatment plants. M. viridans contains ZOOCHLORELLAE. maytansine See MICROTUBULES. mazaedium A type of ascocarp in which the asci disintegrate to release a powdery mass of ascospores (with sterile elements); mazaedia are formed in members of the Caliciales and in Onygena. (The term ‘mazaedium’ may also refer to the spore mass per se.) MBC fungicides See BENZIMIDAZOLES (a). MBL Mannose-binding lectin: see COMPLEMENT FIXATION (c). Mbl protein See CELL CYCLE (b) (determination of shape). MBP Mannose-binding protein, referred to more commonly as MBL (mannose-binding lectin) – see COMPLEMENT FIXATION (c). MBSA Methylated bovine serum albumin. MC29 See AVIAN ACUTE LEUKAEMIA VIRUSES. Mcc plasmid See MICROCINS. McCartney bottle A bottle similar to a UNIVERSAL BOTTLE but which has a narrower neck. McClung Toabe egg-yolk agar (modified) A medium used for the isolation and identification of clostridia and other anaerobes; it permits detection of lecithinase, lipase and proteolytic activity. The medium contains tryptone, yeast extract, glucose, egg yolk, Na2 HPO4 , NaCl, MgSO4 and agar. McDonough feline sarcoma virus See FMS. MCF viruses Mink cell focus-forming viruses: variant MURINE LEUKAEMIA VIRUSES (MuLVs) which can be detected and assayed by their ability to induce foci of transformed cells in monolayer cultures of a mink lung cell line. MCF viruses were originally isolated from mouse strains (e.g. AKR) which show a very high incidence of spontaneous leukaemia. The env gene of an MCF virus resembles a mixture of those of murine ecotropic and xenotropic viruses, and confers on it a DUALTROPIC host range. MCF viruses are believed to have arisen by recombination 461

meat spoilage OTITIS MEDIA or PNEUMONIA. Measles is usually self-limiting, but may be fatal in young infants or in malnourished children; death is usually due to respiratory complications. Life-long immunity usually follows recovery (cf. SUBACUTE SCLEROSING PANENCEPHALITIS). Lab. diagnosis: microscopic examination of smears of the nasal mucosa for epithelial GIANT CELLS; detection of the measles virus in blood, urine or nasal secretions. Chemotherapy: none. Measles immune globulin may be used prophylactically in high-risk patients exposed to measles. Live attenuated vaccines (cf. MR and MMR) may be given to infants and young children. meat spoilage The occurrence, nature and extent of meat spoilage depends on e.g. the initial numbers and types of contaminating microorganisms, the conditions of storage (particularly temperature and oxygen tension), the length of storage, and the nature of the meat itself (e.g. its WATER ACTIVITY, glucose content [see e.g. AEM (1982) 44 521–524], pH). Spoilage may involve slime formation, discoloration, souring, and off-odours (due e.g. to the volatile products of microbial amino acid metabolism). (a) Carcasses. Carcass meat is normally surface-contaminated with bacteria and fungi derived from the animal’s skin, intestine, faeces etc., from soil, and e.g. from the hands and tools of workers. Even under good hygienic conditions, carcasses are likely to carry 102 –105 bacteria/cm2 , but spoilage commonly becomes apparent only after bacterial numbers reach ca. 107 –109 per cm2 . After slaughter, the pH of meat gradually falls as the muscle glycogen is converted to lactic acid – the final pH depending on the amount of glycogen present at the time of death. The final pH of red meats is commonly 5.4–5.8; chicken leg meat normally has a pH of ca. 6.5, although the breast meat usually has a pH of ca. 5.7. Meat from stressed animals has a higher pH and is more susceptible to spoilage – see DFD MEAT. For short-term storage, carcasses may be chilled to e.g. 0–10° C. Below ca. 10° C psychrotrophic spoilage organisms increase greatly in numbers; by contrast, pathogenic organisms (cf. FOOD POISONING) grow very slowly, and their presence is usually not obvious. In most meats, including uncured pig meat and poultry, the commonest spoilage bacteria under aerobic conditions are strains of Pseudomonas [JAB (1982) 52 219–228 (taxonomic study)], often occurring together with smaller numbers of bacteria such as Acinetobacter, Alteromonas, Brochothrix and Lactobacillus spp. Of the spoilage organisms, Pseudomonas spp have the highest growth rate at low temperatures, and this advantage tends to become more marked with decreasing temperature. (In poultry, Acinetobacter replaces Pseudomonas as the commonest spoilage organism at temperatures above ca. 10° C.) However, Brochothrix thermosphacta and Lactobacillus spp, for example, are more tolerant than pseudomonads of low aw , and these may become dominant on drying carcasses. On cured meats (see CURING), e.g. bacon, the commonest spoilage bacteria under aerobic conditions are halophilic, psychrophilic vibrios (e.g. Vibrio costicola) and species of Acinetobacter and Micrococcus; the micrococci are lipolytic and proteolytic, and some strains can reduce nitrite. Fungi found on chilled carcasses include Cladosporium, Penicillium, Mucor, Rhizopus and Thamnidium, and the yeasts Candida, Cryptococcus and Rhodotorula; these may cause e.g. surface discolorations. For long-term storage, temperatures of ca.
12° C to
18° C are often used; the process of freezing kills or damages a proportion of contaminants, although lower temperatures (e.g.
30° C) are less lethal (see FREEZING). At temperatures between ca.
5° C and
10° C fungal contaminants may become important spoilage agents (see e.g. BLACK SPOT sense 1).

(b) Packaged meats. As well as the factors cited above, the nature of spoilage of packaged meats depends on the type of packaging – particularly on the permeability of the packing material to air. Spoilage of chilled red meats typically occurs more rapidly in the presence of oxygen than under vacuum. Under aerobic conditions (e.g. with oxygen-permeable packing film) Pseudomonas spp are the commonest spoilage organisms; Acinetobacter may be present in significant numbers if the pH is above ca. 6.0. Under anaerobic conditions (e.g. in oxygen-impermeable vacuum packs) these organisms are inhibited, permitting the growth of e.g. Lactobacillus spp and Brochothrix thermosphacta; CARBON DIOXIDE per se (ca. 10–20% v/v) inhibits the growth of e.g. Pseudomonas spp, Alteromonas putrefaciens, Acinetobacter sp, and Yersinia enterocolitica, but not of e.g. B. thermosphacta or lactobacilli. (cf. DFD MEAT.) At low temperatures (e.g. 5° C) vacuum-packed cured meats (e.g. bacon) are susceptible to spoilage by e.g. Lactobacillus spp (which may cause e.g. souring) [AvL (1983) 49 327–336]; lactobacilli are resistant to nitrite, smoke (see SMOKING), and low concentrations of salt. At higher salt concentrations, Micrococcus spp may become dominant. Cooked hams and cooked sausage (in which CATALASE has been destroyed) may undergo a type of greening caused by e.g. lactobacilli (especially L. viridescens); these organisms produce H2 O2 which oxidizes the porphyrin ring in meat haem pigments to form a green compound (cf. DFD MEAT). (Higher concentrations of H2 O2 can produce yellow or colourless compounds.) [Book ref. 30.] (See also CANNING; FOOD SPOILAGE; SALAMI; SOFT CORE HAM.) mecA gene See MRSA. MECAM A (synthetic) functional analogue of enterobactin used e.g. in studies on IRON uptake [see e.g. JB (1986) 167 666–680]. mechanical transmission Transmission of a parasite by passive transfer from one host to another, e.g. via a mechanical VECTOR, via contaminated tools or instruments etc. mechanical vector See VECTOR (1). mechanosensitive channel (stretch-activated channel) A channel through the CYTOPLASMIC MEMBRANE which responds to increases in the cell’s turgor pressure by increasing in pore size, thus facilitating efflux of water and certain solutes [JBC (1997) 272 32150–32157]; one example is the MscL channel in Escherichia coli [mechanosensitive channels in E. coli : ARP (1997) 59 633–657]. Such channels occur in many types of bacteria and appear to have an important role in OSMOREGULATION; they open when the cell’s turgor pressure is just below the level at which fatal disruption would occur [EMBO (1999) 18 1730–1737]. [The gating mechanism of the large mechanosensitive channel in Mycobacterium tuberculosis: Nature (2001) 409 720–724.] mecI, mecR1 genes See MRSA. mecillinam (Coactin; amdinocillin) A derivative of 6-b-amidinopenicillanic acid (cf. PENICILLINS) which, in e.g. Escherichia coli, binds exclusively to PBP-2 (see PENICILLIN-BINDING PROTEINS). medallion clamp See CLAMP CONNECTION. median lethal dose Syn. LD50 (q.v.). medical flat A flat-sided glass screw-cap bottle obtainable in various sizes. medicarpin An isoflavonoid PHYTOALEXIN produced e.g. by the broad bean (Vicia faba). (cf. WYERONE.) Medina reaction See LEPROMIN TEST. 462

meiosis medium In microbiology: any liquid or solid preparation made specifically for the growth, storage or transport of microorganisms or other types of cell. Growth media for microorganisms may be used e.g. for the initiation of a CULTURE (or a SUBCULTURE), for ENRICHMENT, or for diagnostic (identification) tests – i.e. tests in which the identity of a given organism may be deduced from the characteristics of its growth in or on particular media. (See also TRANSPORT MEDIUM.) Specialized media are used for the growth/maintenance of mammalian (and other) cells in TISSUE CULTURE (q.v.). Before use, a medium is normally STERILE (sense 1). Many chemolithautotrophic bacteria can be cultured in simple aqueous media containing mainly, or only, mixtures of inorganic salts. Nutritionally undemanding heterotrophs can be grown on/in a range of culture media (see e.g. NUTRIENT BROTH and PETONE WATER). Nutritionally ‘fastidious’ heterotrophs may be grown on an ENRICHED MEDIUM. Strict anaerobes are often cultured on ‘prereduced’ media (see ANAEROBE). Solid media usually consist of liquid media which have been solidified (‘gelled’) with an agent such as AGAR or GELATIN; other gelling agents include e.g. ALGINATE, Gelrite (see GELLAN GUM), and PLURONIC POLYOL F127. (See also SILICA GEL.) Solid media (such as e.g. NUTRIENT AGAR) may be used in order to obtain colonies (see COLONY) of a given organism; colonies may be required for identification purposes or e.g. for the determination of viable cell counts (see COUNTING METHODS). Media containing an unusually high concentration of solidifying agent (e.g. stiff AGAR) are used e.g. to inhibit SWARMING; those containing less than normal concentrations of solidifying agent (e.g. semi-solid or ‘sloppy’ agar) may be used e.g. for CRAIGIE’S TUBE METHOD. Basal medium. One which, without supplement, can support the growth of various nutritionally undemanding species; see e.g. NUTRIENT BROTH. Defined medium. One in which all the constituents (including trace substances) are quantitatively known. Differential medium. A solid medium on/in which different types of organism may be distinguished by their different forms of growth; see e.g. MACCONKEY’S AGAR; SS AGAR. Diphasic medium. See DIPHASIC MEDIUM. Enriched medium. See ENRICHED MEDIUM. Enrichment medium. See ENRICHMENT MEDIUM. Inhibitory medium. One containing certain constituent(s) which suppress the growth of certain type(s) of microorganism. Maintenance medium. One used for the initial growth and subsequent storage (under conditions of minimal growth) of microorganisms or other cells. For microorganisms, a maintenance medium is used to prepare a CULTURE of the given organism which is then stored either at room temperature or under refrigeration; subculture is required at intervals ranging from 1 to 12 months. Ideally, the constituents of a maintenance medium are the minimum consistent with the need to maintain viability of the organisms. Examples: COOKED MEAT MEDIUM and DORSET’S EGG. (See also TISSUE CULTURE.) Pre-reduced medium. See ANAEROBE. Selective medium. One which allows or encourages the growth of some type(s) of organism in preference to others. The term usually refers to media such as DCA, MacConkey’s agar (which generally supports the growth of enteric – but not nonenteric – bacteria), and all the various types of enrichment media; however, all media are selective to some extent. Test medium. One used for diagnostic (identification) tests. Test media are often made by incorporating additional substance(s) into standard or modified liquid or solid media; often a

is included to monitor certain aspects of metabolic activity. Examples: KCN BROTH, LITMUS MILK, TSI AGAR. Transport medium. See TRANSPORT MEDIUM. MEE MULTILOCUS ENZYME ELECTROPHORESIS. mefA gene See MACROLIDE ANTIBIOTICS. mefloquine See AMINOQUINOLINES and MALARIA. megacins See BACTERIOCIN. megacolon See CHAGAS’ DISEASE. megalomycin See MACROLIDE ANTIBIOTICS. Megasphaera A genus of Gram-negative bacteria (family VEILLONELLACEAE) which occur e.g. in the RUMEN and in the human intestine. Cells: cocci, ca. 2.0–2.5 µm diam., commonly occurring in pairs. The fermentation of glucose yields mainly caproate, while that of lactate yields acetate, propionate, valerate, C4 fatty acids, much CO2 and a little H2 – but little or no caproate. GC%: ca. 54. Type species: M. elsdenii (formerly Peptostreptococcus elsdenii ). Megatrypanum A subgenus of TRYPANOSOMA within the STERCORARIA; species are parasitic in e.g. cattle and sheep. The organisms are large, sometimes greater than 100 µm in length; the kinetoplast is situated approximately mid-way between the nucleus and the posterior end of the cell, and there is a free flagellum. T . (M.) theileri occurs in cattle, and is probably transmitted by contaminative infection of mucous membranes etc with metacyclic forms via tabanid vectors; it is generally non-pathogenic. T . (M.) melophagium occurs in sheep, and T . (M.) theodori occurs in goats. megrims Syn. STAGGERS. MEIA (microparticle enzyme immunoassay) See LCR. meiocyte A cell whose nucleus undergoes MEIOSIS. meiosis (reduction division) The process in which a eukaryotic nucleus divides into nuclei whose ploidy is lower than that of the parent nucleus (typically, haploid nuclei being formed from diploid nuclei) and in which RECOMBINATION usually occurs. (cf. MITOSIS.) Meiosis occurs e.g. during the formation of gametes from diploid cells, and at the inception of haplophase in those organisms which exhibit an ALTERNATION OF GENERATIONS. (See also GAMETIC MEIOSIS; SPORIC MEIOSIS; ZYGOTIC MEIOSIS.) The best-known form of meiosis is that which occurs in higher animals; other forms of meiosis (which differ in one or more aspects) occur in various microorganisms. Meiosis in higher animals involves two distinct nuclear divisions: the first meiotic division (meiosis I) and the second meiotic division (meiosis II) – each division exhibiting a prophase, metaphase, anaphase and telophase. (cf. MITOSIS.) Prophase I. Individual chromosomes, each having previously replicated to form two chromatids, become visible as long, single threads (leptotene stage). In the zygotene stage each chromosome pairs, lengthwise, with its HOMOLOGUE, the pair of closely adjacent chromosomes being called a bivalent ; the pairing of chromosomes (synapsis) involves the SYNAPTONEMAL COMPLEX. In this stage and/or the next (pachytene) stage CROSSING OVER occurs between pairs of non-sister chromatids. In the diplotene stage each chromosome begins to separate from its homologue – but the chromosomes of each homologous pair remain in contact at sites of crossing over (see CHIASMA). In the final stage of prophase I (diakinesis) the chromosomes condense, and each homologous pair is seen to consist of four chromatids (i.e., a tetrad ). By the end of diakinesis the nucleolus and nuclear membrane have disintegrated. Metaphase I. Homologous pairs of chromosomes form a layer at the equator of a microtubular spindle (as in MITOSIS). Anaphase I. The two chromosomes in each homologous pair move to opposite poles of the spindle. PH INDICATOR

463

meiosporangium L-arabinose.

The disease occurs primarily in tropical regions, particularly in S. E. Asia. Infection usually occurs via wounds or (infrequently) by inhalation of contaminated dust or by ingestion. The causal organism occurs as a free-living bacterium in both soil and water; infection by B. (P.) pseudomallei (through cuts, abrasions) has been reported to occur more often during the wet season. Person-to-person transmission of the disease has been reported [Lancet (1991) 337 1290–1291]. In man, the disease is very variable, ranging from a local suppurative lesion at the site of infection to an acute, fulminating septicaemia. The disease may flare up after long periods of time (as found e.g. in American veterans of the Vietnam war). In a recent study of melioidosis in Taiwan, all the isolates of B. (P.) pseudomallei were reported to be susceptible to the following antibiotics: amoxycillin-clavulanate, piperacillintazobactam (tazobactam is a b-lactamase inhibitor), imipenem and meropenem [EID (2001) 7 428–433]. Meliola See BLACK MILDEWS. Melissococcus See EUROPEAN FOULBROOD. Melittangium See MYXOBACTERALES. Melksham virus See SMALL ROUND STRUCTURED VIRUSES. Melolontha melolontha EPV See ENTOMOPOXVIRINAE. Melosira A genus of freshwater and marine centric DIATOMS in which the cylindrical cells (diam. ca. 5–100 µm) are typically joined valve-to-valve to form long chains. In many species the valves are highly pleomorphic; in e.g. M. islandica valve morphology apparently depends on nutrient (phosphorus and silicon) levels [Limn. Ocean. (1985) 30 414–418]. Sexual reproduction is oogamous. melting (of DNA) See HELIX–COIL TRANSITION. Meltzer’s reagent A mycological stain used e.g. for studying spore septation and ascus structure; it consists of iodine (0.5 g), potassium iodide (1–1.5 g), and chloral hydrate (20 g) in distilled water (20 ml). membrane anchor sequence See SIGNAL HYPOTHESIS. membrane attack complex See COMPLEMENT FIXATION (a). membrane co-factor protein See COMPLEMENT FIXATION (b). membrane filter See FILTRATION. membrane fusion protein (MFP) In certain transport systems of Gram-negative bacteria: a protein which appears to act as a link between inner and outer membranes (see e.g. ABC EXPORTER and RND). membrane-inlet mass spectrometry A method used for the direct and continuous monitoring of gas(es) dissolved in a liquid medium, e.g. a bacterial culture. Essentially, a hydrophobic membrane (e.g. PTFE – see FILTRATION) separates the liquid from a vacuum; dissolved gas(es) pass through the membrane into the vacuum and thence into the mass spectrometer. [MS (1984) 1 200–203; Book ref. 132, pp. 239–262; some applications: Book ref. 132, pp. 271–294.] membrane potential See CHEMIOSMOSIS. membrane trigger hypothesis See SIGNAL HYPOTHESIS. membranelle (protozool.) A discrete tuft or band of closely packed, apparently coherent cilia which behave as a unified organelle. (cf. SYNCILIUM.) The term is sometimes used to refer specifically to any one of the serially arranged membranelles of the AZM (q.v.). (See also COMPOUND CILIATURE.) membranous croup Syn. DIPHTHERIA. memory cells (immunol.) Lymphocytes which have had initial contact with specific antigen and which, on subsequent challenge with antigen, can give a rapid and heightened response (compared with the response that followed initial challenge).

Telophase I. Each of the two groups of chromosomes becomes enclosed by a nuclear membrane. The interval between the first and second meiotic divisions is called interkinesis or interphase II. The second meiotic division is analogous to mitosis, and consists of prophase II, metaphase II, anaphase II and telophase II. [Control of meiosis: SEBS (1984) 38.] meiosporangium A SPORANGIUM within which MEIOSIS occurs (see e.g. ALLOMYCES). meiospore A haploid spore formed by meiotic cell division. (See also ALTERNATION OF GENERATIONS.) meiotic Of or pertaining to MEIOSIS. Mel B Syn. melarsoprol (see ARSENIC). Mel T See ARSENIC (a). Melampsora A genus of homoxenous and heteroxenous rust fungi (class UREDINIOMYCETES) which typically form caeomatoid aecia, peridiate uredia, and sessile teliospores. (See also FLAX RUST.) Melanconiales An order of fungi (class COELOMYCETES) in which the vegetative mycelium occurs within the substrate or host, and the conidiomata are formed in the superficial layers of the host, becoming erumpent at maturity; mature conidiomata are either acervuli or sporodochia. Some species are important plant pathogens (see e.g. ANTHRACNOSE). Genera include COLLETOTRICHUM, Cylindrosporium, Entomosporium, Marssonina and Pestalotia. (See also DIPLOCARPON.) melanin A high-MWt, amorphous polymer of indole quinone; melanins are pigments found in plants, animals (including the skin and hair in man), insects etc, and also in certain microorganisms (e.g. in actinomycetes, in hyphal walls of dematiaceous fungi, in the spore walls of e.g. Mucor spp). Melanins are relatively non-specific enzyme inhibitors; they may e.g. protect fungal cell walls from enzymic attack [Book ref. 38, pp. 373–374] and prevent cell lysis in old cultures. Melanins in plants may play a role in resistance to fungal infection. The first step in melanin biosynthesis involves the ohydroxylation of L-tyrosine (by tyrosinase) to form L-3,4dihydroxyphenylalanine (L-dopa); L-dopa is used e.g. in the treatment of Parkinson’s disease, and attempts have been made to adapt melanin-producing microorganisms for the commercial production of L-dopa [Book ref. 31, p. 567]. Melanogaster See GASTEROMYCETES (Melanogastrales). Melanogastrales See GASTEROMYCETES. Melanoplus sanguinipes EPV See ENTOMOPOXVIRINAE. Melanospora See SORDARIALES. Melanotaenium A genus of smut fungi (order USTILAGINALES) which are parasitic on the pteridophyte Selaginella. melarsoprol See ARSENIC. Melasmia A genus of fungi of the COELOMYCETES. (See also RHYTISMA.) melezitose A trisaccharide – a-D-glucopyranosyl-(1 ! 3)-b-Dfructofuranosyl-(2 $ 1)-a-D-glucopyranoside – found in nature e.g. in certain HONEYDEWS. It can be metabolized e.g. by certain Lactobacillus spp. Hydrolysis of melezitose by a-glucosidase yields glucose and turanose (a-D-glucopyranosyl-(1 ! 3)-Dfructose). melibiose A reducing disaccharide: a-D-galactopyranosyl-(1 ! 6)-D-glucopyranose, formed from RAFFINOSE by the action of b-fructosidase (invertase). In Escherichia coli melibiose uptake occurs by NaC /melibiose symport (see ION TRANSPORT). melioidosis A disease of man and animals (particularly rodents) caused by Burkholderia (Pseudomonas) pseudomallei – commonly by strains of the biotype that are unable to assimilate 464

mercury nerve-tissue rabies vaccines (e.g. Semple vaccine); and in certain non-microbial diseases (e.g. cerebral tumours). (See also MENINGOENCEPHALITIS.) meningococcus Neisseria meningitidis. meningoencephalitis Inflammation of the brain and its meninges (cf. ENCEPHALITIS and MENINGITIS). Primary amoebic meningoencephalitis is a human disease which affects mainly children and young adults and is usually fatal. It is usually caused by Naegleria fowleri. Infection occurs via the nasal mucosa and is usually associated with swimming in e.g. freshwater lakes rich in organic matter. Symptoms may include headache, fever, vomiting, disturbances to taste, smell and vision, and coma; death may occur within ca. 72 h. Amoebae of the Acanthamoeba-Hartmannella group may cause a subacute or chronic granulomatous meningoencephalitis. Lab. diagnosis: identification of amoebae in the CSF. Chemotherapy: e.g. amphotericin B (see also MICONAZOLE). meningoencephalomyelitis See ENCEPHALITIS. meningomyelitis Inflammation of the spinal cord and its meninges (cf. MENINGITIS). Meniscus A genus of Gram-negative, anaerobic (but aerotolerant) bacteria which occur e.g. in anaerobic digester sludge. The cells are capsulated, straight or curved, non-motile rods, 0.7–1.0 ð 2.0–3.0 µm, which contain gas vacuoles. The organisms are chemoorganotrophs with a strictly anaerogenic fermentative metabolism; growth requirements include vitamin B12 , thiamine, and a raised partial pressure of CO2 . Optimum growth temperature: ca. 30° C. GC%: ca. 45. Type species: M. glaucopsis. [Book ref. 22, pp. 135–137.] Menoidium See EUGLENOID FLAGELLATES. menthol See PHENOLS. mepacrine Syn. QUINACRINE. merbromin See MERCURY. 2-mercaptoethanesulphonic acid Coenzyme M: see METHANOGENESIS. mercaptoethanol (HSCH2 CH2 OH) A reagent used e.g. to reduce disulphide bonds in proteins (e.g. immunoglobulins – see FAB PORTION). Mercurochrome See MERCURY. mercury (as an antimicrobial agent) Mercury is a HEAVY METAL whose compounds include many effective antimicrobial agents; such agents are typically reversibly microbistatic, and they have little or no effect on the viability of bacterial endospores – though they can delay germination. The functional part of an antimicrobial mercurial is the mercury cation or the mercury-containing moiety; antimicrobial activity may involve the binding of these entities to certain groups (particularly thiols – but also e.g. amides and amines, purines and pyrimidines) in e.g. enzymes, cell walls, cytoplasmic membranes and nucleic acids. Microbistatic activity can be reversed with e.g. thiols – which probably compete with the mercury-binding sites of the organisms. In bacteria, resistance to mercurials can be plasmid-mediated. Inorganic mercurials are toxic and irritant to tissues; their activity is readily inhibited or reversed by organic matter (e.g. blood or serum). Mercuric chloride (corrosive sublimate) has been used for the disinfection of inanimate objects when other methods are unsuitable, and as a preservative for e.g. paper and timber. Mercurous chloride (calomel) has restricted use as a fungicide in horticulture – e.g. as a control against clubroot. Yellow mercuric oxide has been used in ointments for the treatment of conjunctivitis and blepharitis. Ammoniated mercury (aminomercuric chloride; white precipitate; HgNH2 Cl) has been used in ophthalmic preparations and for the treatment of superficial mycoses.

Unlike other lymphocytes in the circulation, memory cells persist for long periods of time; they are also distinguishable by certain cell-surface antigens, e.g. CD44. (See also ANTIBODY FORMATION.) menadione See QUINONES. menaquinones See QUINONES. Mendosicutes A proposed division of the PROCARYOTAE comprising the single class ARCHAEOBACTERIA. mengovirus See CARDIOVIRUS. meningitis Inflammation of the meninges (membranes covering the brain and spinal cord). Meningitis may be of non-microbial causation, or it may result from primary or secondary infection by any of a range of microorganisms which gain access to the meninges via the blood or lymph systems, head wounds, or paranasal sinuses. (a) Bacterial meningitis. Symptoms typically include a severe, throbbing headache, stiff neck, fever, delirium and coma; bacterial meningitis may be rapidly fatal. Lab. diagnosis: the pathogen can often be detected by microscopic examination of a Gram-stained smear of CSF sediment. Meningococcal meningitis (‘epidemic meningitis’) – caused by Neisseria meningitidis (the meningococcus) – occurs sporadically or in epidemics. Transmission occurs by direct contact or by droplet infection; asymptomatic carriers harbour meningococci in the nasopharynx. Incubation period: ca. 2–10 days. Onset is usually abrupt, with rapid progression to confusion and coma; meningitic symptoms are often accompanied by petechial or purpuric skin lesions which may become gangrenous. Mortality rates: ca. 25–75% in untreated cases, ca. 7–10% in treated cases. A severe, fulminating form involving cyanosis, coma, and skin and adrenal haemorrhages (Waterhouse–Friderichsen syndrome) may be fatal within a few hours. Chemotherapy: benzylpenicillin, chloramphenicol. Rifampicin can eliminate meningococci from carriers. [A meningococcal C vaccine in teenagers: Lancet (2003) 361 675–676.] Haemophilus influenzae type b is a common cause of bacterial meningitis in infants and young children, often secondary to otitis media, pneumonia or viral respiratory disease. Mortality rates (treated cases): ca. 3–10%. Chemotherapy: e.g. chloramphenicol. Pneumococcal meningitis (caused by Streptococcus pneumoniae) occurs mostly in infants and the elderly or debilitated. It is commonly associated with pneumococcal pneumonia, but may follow otitis media, head wounds etc. Mortality rates: ca. 20–70%. Chemotherapy: e.g. benzylpenicillin, chloramphenicol. Various other bacteria can cause meningitis in adults – e.g. other streptococci, staphylococci, Acinetobacter calcoaceticus, Listeria monocytogenes, enterobacteria. Neonates are particularly vulnerable to meningitis caused by Escherichia coli and other enterobacteria, group B streptococci, Staphylococcus aureus, L. monocytogenes, Flavobacterium meningosepticum etc; mortality rates may be high, and motor or intellectual impairment often persists in survivors. (b) Aseptic meningitis is generally a benign, self-limiting condition characterized by a lymphocytic infiltration of the meninges and raised protein levels in the CSF. It is usually caused by a virus – commonly mumps virus or enteroviruses (e.g. echoviruses or coxsackieviruses), also e.g. ENCEPHALITIS viruses, herpes simplex virus and LCM VIRUS. A lymphocytic meningitis may also occur in e.g. CRYPTOCOCCOSIS, LEPTOSPIROSIS, SYPHILIS and TUBERCULOSIS; following administration of 465

meriOrganic mercurials are generally less toxic (to man), are less irritant, and are typically more effective antimicrobial agents. Mercurochrome (merbromin; disodium 20 ,70 -dibromo-40 hydroxymercurifluorescein) was one of the first organic mercurial antiseptics, but it is among the least effective and is no longer widely used. Nitromersol (Metaphen; 4-nitro-3-hydroxymercurio-cresol anhydride) is used e.g. in antimicrobial solutions and ointments for the treatment of e.g. conjunctivitis and superficial mycoses. (See also THIOMERSAL.) Phenylmercuric borate, nitrate and acetate (the most soluble) all have similar antimicrobial properties; they have been used as antiseptics, as preservatives for pharmaceutical preparations, paper, wood etc, and as seed dressings. Microbial resistance to mercury and organomercurials: see HEAVY METALS. meri- Combining form signifying ‘part’. Meria See HYPHOMYCETES and NEMATOPHAGOUS FUNGI. Merismopedia A phycological genus of unicellular ‘blue-green algae’ (Chroococcales) in which the cells occur (in nature) in rectangular ‘plates’. See SYNECHOCYSTIS. meristem A region of an organism at which new, permanent tissue is formed, i.e., a ‘growth region’ of a plant or multicellular microorganism. meristematic nodules See ROOT NODULES. meristoderm In certain algae (e.g. Laminaria): a surface layer of cells which, on division, gives rise to an increase in the thickness of the thallus. meristogenous development (mycol.) The development of certain fungal structures (e.g. pycnidia, stromata) by the proliferation and differentiation of a small number of adjacent cells in a single hypha. (cf. SYMPHOGENOUS DEVELOPMENT.) mermaid’s wine-glass See ACETABULARIA. mero- Combining form signifying ‘part’. Merocystis See EIMERIORINA. merodiploid See DIPLOID. merogony Syn. SCHIZOGONY. meromictic lake A permanently stratified lake in which only the upper layers undergo turnover, the lower layer (hypolimnion) being typically stagnant, anaerobic, and rich in sulphide. (cf. HOLOMICTIC LAKE.) meropenem A broad-spectrum 1-b-methylCARBAPENEM antibiotic. (See also ERTAPENEM.) merosporangium An elongated (‘cylindrical’) SPORANGIUM containing either a single spore or a small number of spores in a row; merosporangia are formed e.g. by Piptocephalis and Syncephalastrum. merozoite See SCHIZOGONY. merozygote A bacterium which is part DIPLOID, part haploid; it may be formed in certain processes in which chromosomal genes pass from one bacterium (the donor) to another (the recipient) – see CONJUGATION, TRANSDUCTION and TRANSFORMATION. The genetic complement of a merozygote comprises the endogenote (the recipient’s own chromosome) and the fragment of genetic material (the exogenote) received from the donor. If corresponding ALLELES in the endogenote and exogenote are identical the merozygote is said to be a homogenote; if not, it is said to be a heterogenote. merthiolate Syn. THIOMERSAL. Merulius See APHYLLOPHORALES (Corticiaceae). (cf. SERPULA.) MES A pH buffer based on 2-(N-morpholino)-ethanesulphonic acid. Meselson–Radding model See RECOMBINATION (Figure 2). mesocyst See CYST (b).

Mesodinium See GYMNOSTOMATIA. meso-inositol See INOSITOL. mesokaryotic See DINOFLAGELLATES. mesophile An organism whose optimum growth temperature lies within a range generally accepted as ca. 20–45° C; bearing in mind the definition of PSYCHROPHILE, it would be reasonable to extend this range to 15–45° C. mesoplankton See PLANKTON. mesoporphyrins See PORPHYRINS. mesosaprobic zone See SAPROBITY SYSTEM. mesosomes (chondrioids) Intracellular membranous structures, apparently continuous with the CYTOPLASMIC MEMBRANE, which have been observed in electron micrographs of many bacteria. In Gram-positive species they may appear e.g. as parallel or concentric lamellae or as vesicles (perhaps tubules) which may be interconnected; in Gram-negative bacteria mesosomes appear to be smaller and less intricate, and are often seen as simple invaginations of the cytoplasmic membrane. Mesosomes are commonly associated with the developing septum in a dividing cell, but their function – if any – is unknown; they are widely believed to be artefacts derived from the cytoplasmic membrane during preparation of specimens for electron microscopy [see e.g. AvL (1984) 50 433–460 (439–443)]. (cf. INTRACYTOPLASMIC MEMBRANES.) Mesostigma See MICROMONADOPHYCEAE. Mesotaenium A genus of saccoderm DESMIDS. messenger RNA See MRNA. messenger RNA-interfering complementary RNA See ANTISENSE RNA. metabasidium A developing BASIDIUM at the stage at which MEIOSIS occurs, or that part of a developing basidium in which meiosis occurs. According to species, the metabasidium may be a later stage of (but morphologically identical to) the PROBASIDIUM, or it may arise – as a separate structure – from the probasidium. According to species, a metabasidium gives rise to sterigmata (each STERIGMA bearing one terminal basidiospore) or to basidiospores borne directly on its surface (i.e., without sterigmata). A metabasidium may be septate (as e.g. in Tremella) or aseptate (as e.g. in Agaricus). In e.g. rust fungi the metabasidium is a septate structure (D ‘promycelium’) which grows out from the teliospore. metabiosis The phenomenon in which one organism alters environmental conditions in such a way as to allow the growth of another or others; e.g., utilization of oxygen by aerobic organisms may create anaerobic microenvironments in which strict anaerobes can grow. metabisulphites See SULPHUR DIOXIDE. metabolic inhibition test Any test in which an agent is detected or quantified by its ability to inhibit metabolic activity. For example, a toxin, virus, or other cytocidal agent can be assayed by determining its ability to inhibit the normal metabolic processes in a tissue culture; normally, the medium in a tissue culture becomes acidic with time, and the titre of the cytocidal agent can be estimated by determining the highest dilution of the agent which delays or inhibits acidification of the medium. metaboly See EUGLENA. metachromasy The phenomenon in which certain substances (termed chromotropes) develop a colour different to that of the dye used to stain them. See e.g. METACHROMATIC GRANULES. metachromatic dye Any DYE which gives rise to METACHROMASY when used to stain chromotropic substances. metachromatic granules Intracellular POLYPHOSPHATE-containing granules which, on staining with certain basic dyes (e.g. polychrome methylene blue or toluidine blue – see ALBERT’S STAIN), 466

Methanobacteriaceae exhibit METACHROMASY. [Composition of metachromatic granules: JB (1984) 158 441–446.] metachronal waves (protozool.) Waves which may be seen on the surface of a ciliate due to the beating of its cilia – an effect similar to that produced by an intermittent breeze on a field of barley or tall grass. While the cilia of a given ciliate beat with similar or identical frequencies, they do not, in general, beat synchronously – i.e., all the cilia do not pass simultaneously through the same phase of the beat cycle (see CILIUM). Instead, ciliary beating is usually metachronous: adjacent cilia pass through slightly different phases of the beat cycle at any given instant – the phase difference between a given cilium and other cilia in a KINETY increasing and decreasing cyclically with distance from the given cilium. (This results in the smooth motion characteristic of ciliates.) In one type of metachrony (symplectic metachrony) a sequence of cilia which, at a given instant, are all passing through (different stages of) the effective stroke of the beat cycle, tend to bunch together to form the crest of a metachronal wave; the crests of such waves move in the direction of the effective stroke. In antiplectic metachrony, cilia passing through the effective stroke do not bunch together, and the metachronal crests move in a direction opposite to that of the effective stroke. In both symplectic and antiplectic metachrony the effective and recovery strokes occur in the plane of the kinety; these types of metachrony are termed orthoplectic metachrony. In diaplectic metachrony the effective and recovery strokes occur in a plane perpendicular to the kinety; the effective stroke may be to the right (dexioplectic metachrony) or to the left (laeoplectic metachrony) when looking in the direction of the metachronal wave. Symplectic metachrony is quite rare in ciliates, but antiplectic and diaplectic (dexioplectic) types of metachrony are quite common. metacyclic forms (metatrypanosomes) Trypanosomes, infective for the vertebrate host, which develop at the end of the period of cyclical development in the invertebrate vector; they are trypomastigote in form, with or without a short free flagellum. In Trypanosoma vivax a ‘surface coat’ (see VSG) has been reported to occur on metacyclic forms prior to contact with the mammalian host [Parasitol. (1986) 92 75–82]. Metacystis See GYMNOSTOMATIA. Metadinium See ENTODINIOMORPHIDA. metal leaching See LEACHING. metalaxyl See PHENYLAMIDE ANTIFUNGAL AGENTS. metalimnion (thermocline) In a lake: the layer of water between the EPILIMNION and the HYPOLIMNION; this layer is characterized by the maximum rate of decrease in temperature with depth. Metallogenium A genus of IRON BACTERIA. The organisms have been reported to be capable of passing through a filter of pore size 0.2 µm and of inhibiting various prokaryotic and eukaryotic microorganisms when cultured with them [Curr. Micro. (1984) 11 349–356]. metalloporphyrins See PORPHYRINS. metallothionein A cysteine-rich, low-MWt, inducible protein which binds (and may detoxify) HEAVY METAL ions; metallothioneins from a range of organisms (e.g. Synechococcus, Neurospora, Saccharomyces, crab, horse, man) are structurally similar. metaphase See MITOSIS and MEIOSIS. metaphase plate See MITOSIS. Metaphen See MERCURY. Metarhizium A genus of entomopathogenic fungi (class HYPHOMYCETES). M. anisopliae can infect a wide variety of insects; it

produces depsipeptide entomotoxins (destruxins) which apparently play an important role in pathogenesis. M. anisopliae has been used for the BIOLOGICAL CONTROL of e.g. froghoppers (Mahanarva posticata) in Brazilian sugar-cane plantations. metastasis (med.) The dissemination of disease from a localized site in the body, with the formation of new foci at distant sites. (Usually used in the context of CANCER, but also of certain infectious diseases – e.g. TUBERCULOSIS.) (Hence verb metastasize, adj. metastatic.) metatrypanosomes Syn. METACYCLIC FORMS. Metchnikovella See RUDIMICROSPOREA. methacycline See TETRACYCLINES. metham sodium (vapam) Sodium N-methyl-DITHIOCARBAMATE (CH3 .NH.CS.SNa), a soil fumigant which, in soil, breaks down to form the volatile methyl-isothiocyanate. (cf. DAZOMET, QUINTOZENE.) methanal Syn. FORMALDEHYDE. methane monooxygenase (MMO) A MONOOXYGENASE which occurs in methanotrophs (see METHYLOCOCCACEAE) and which catalyses the oxidation of methane to methanol by molecular oxygen; MMO can also catalyse the oxidation of substrates such as n-alkanes and n-alkenes: e.g., propene (propylene) is oxidized to 1,2-epoxypropane. (See also CO-METABOLISM.) MMO may be ‘particulate’ (i.e., membrane bound) or soluble, depending on growth conditions. Thus, e.g., in cells of Methylococcus capsulatus and ‘Methylosinus trichosporium’ grown on methane, the MMO is soluble or particulate according to whether the culture medium contains low (e.g. 1 µM) or high (e.g. 5 µM) levels of Cu2C respectively. However, in M. capsulatus only particulate MMO is formed when growth occurs on methanol – in this case an increase in the level of Cu2C enhancing MMO activity [JGM (1985) 131 155–163]. The soluble MMO of M. capsulatus is a three-component enzyme comprising proteins A (believed to be the oxygenase [JBC (1984) 259 53–59]), B and C, and that of ‘Methylosinus trichosporium’ is apparently similar. The substrate specificities of particulate and soluble MMOs may differ appreciably. Thus, e.g. the soluble MMO of ‘M. trichosporium’ can oxidize n-alkanes, n-alkenes, aromatic and alicyclic compounds, while the particulate MMO of the same organism cannot oxidize aromatic or alicyclic substrates [JGM (1984) 130 3327–3333]. In various types of methanotroph the reducing power requirement for MMO activity in vitro (i.e. in cell extracts) appears to be satisfied by NADH for both the soluble and particulate forms of the enzyme. However, it has been proposed that the reducing power needed for in vivo particulate MMO activity in ‘M. trichosporium’ may be derived from a reduced c-type cytochrome. It has been suggested that reducing power for in vivo particulate MMO activity in M. capsulatus may be supplied by an electron transfer protein (e.g. an Fe–S protein) the reduction of which depends on reversed electron transport [JGM (1983) 129 3487–3497]. methane production See METHANOGENESIS. methane utilization See METHANOTROPHY. Methanobacillus omelianskii A syntrophic association of two species of prokaryote: Methanobacterium bryantii and an obligate proton reducer (the ‘S’ organism) which oxidizes ethanol to acetate and hydrogen gas. Methanobacteriaceae A family of METHANOGENS (order METHANOBACTERIALES); two genera: METHANOBACTERIUM and METHANOBREVIBACTER. (This family formerly included all the methane-producing species.) 467

Methanobacteriales Methanobacteriales An order of METHANOGENS comprising those species whose cell wall contains PSEUDOMUREIN. Two families: METHANOBACTERIACEAE, METHANOTHERMACEAE. Methanobacterium A genus of facultatively autotrophic archaeans (family METHANOBACTERIACEAE). Cells: non-motile rods. Methane may be produced from carbon dioxide and hydrogen and/or from formate. GC% ca. 33–50. M. bryantii. Mesophilic. Cells: morphologically indistinguishable from M. formicicum (see below), but the organisms cannot use formate. Growth is stimulated by acetate and B vitamins. (See also METHANOBACILLUS OMELIANSKII.) M. formicicum. Cells: round-ended rods, ca. 0.6 ð 2–15 µm, often in chains. Formate can be used as an electron donor, and acetate stimulates growth. M. thermoautotrophicum. Thermophilic (opt. temperature: 65–70° C). Formate is not metabolized. Methanobrevibacter A genus of archaeans of the family METHANOBACTERIACEAE. Cells: cocci or short rods, often in pairs or chains. Mesophilic. Methane may be produced from carbon dioxide and hydrogen and/or from formate. GC% ca. 27–32. M. arboriphilus. A facultative autotroph which occurs e.g. in soil (see also WETWOOD). Formate is not used. M. ruminantium. Cells: rods, ca. 0.7 ð 2.0 µm, often in chains. Habitat: the RUMEN. Methane can be formed from carbon dioxide and hydrogen or from formate. Strain M-1 has been used for the BIOASSAY of coenzyme M. M. smithii. Morphologically similar to M. ruminantium. Coenzyme M is not required for growth. methanochondrion A term proposed for the apparent organelle formed (in a number of methane-producing archaeans) from invaginated cytoplasmic membrane and assumed to be the site of methanogenesis. (Such a structure is not invariably present in methanogenic species [CJM (1984) 30 594–604].) Methanococcaceae See METHANOCOCCALES. Methanococcales An order of METHANOGENS comprising one family (Methanococcaceae) and one genus, METHANOCOCCUS. Methanococcoides A genus of METHANOGENS (see METHANOSARCINACEAE). The cells of M. methylutens are non-flagellated cocci (ca. 1 µm diam.); the cell wall consists of an S LAYER only. Methanol and methylamine are methanogenic substrates. GC%: ca. 42. Methanococcus A genus of mesophilic and thermophilic archaeans (order METHANOCOCCALES) which occur e.g. in saltmarsh sediments and marine muds. Cells: motile cocci in which the cell wall consists solely of an S LAYER; the GRAM REACTION is negative. Methane is typically produced from carbon dioxide and hydrogen and/or from formate. Most species (but not M. voltae) can grow autotrophically. (The original type species, M. mazei, differs markedly from the other species, and has been transferred to METHANOSARCINA (Methanosarcina mazei ), Methanococcus vannielii being designated the new type species of the (conserved) genus Methanococcus [IJSB (1986) 36 491].) GC%: ca. 30–33. M. jannaschii. Thermophilic (optimum: 86° C). Methane is produced from carbon dioxide and hydrogen, but not from formate. The growth rate is the highest of all known methanogens (doubling time: 30 min). Isolated from a HYDROTHERMAL VENT. M. maripaludis. Cells 1.2–1.6 µm diam. Mesophilic. M. mazei. See METHANOSARCINA. M. thermolithotrophicus. Cells ca. 1.5 µm diam. Thermophilic (optimum: 65° C). M. vannielii. Cells ca. 3–4 µm diam. Mesophilic. Methane is produced from carbon dioxide and hydrogen and from formate.

M. voltae. Cells ca. 0.5–3.0 µm diam. Mesophilic. Growth is optimal in 0.4 M NaCl. Methane is produced from carbon dioxide and hydrogen and from formate. methanofuran See METHANOGENESIS. methanogen Any member of the domain ARCHAEA which can carry out METHANOGENESIS; all known methanogens are obligate anaerobes which occur e.g. in muds and in the RUMEN (some forming close physical associations with protozoa [MS (1986) 3 100–105]). (See also ANAEROBIC DIGESTION and WETWOOD.) Methanogens have been classified in three orders (METHANOBACTERIALES, METHANOCOCCALES, METHANOMICROBIALES) on the basis of 16S rRNA sequence analysis. Many methanogens can grow chemolithoautotrophically in mineral salts solution with carbon dioxide and hydrogen (although some need e.g. acetate and amino acids). Methanogens are not necessarily confined to simple substrates such as acetate, methanol and methylamines; thus, pure cultures of e.g. Methanospirillum can be grown on 2-propanol and certain other alcohols [AEM (1986) 51 1056–1062]. The methanogens have been divided into two groups: group I (carbon dioxide and hydrogen, or formate, typically used), and group II (carbon dioxide and hydrogen, or formate, typically not used); group II includes the family METHANOSARCINACEAE [AvL (1984) 50 557–567]. Autotrophic carbon dioxide fixation apparently occurs via a pathway resembling that used for the synthesis of acetylCoA from carbon dioxide in ACETOGENESIS, although formyl tetrahydrofolate synthase does not seem to be involved. AcetylCoA appears to be reductively carboxylated to pyruvate – which is converted to phosphoenolpyruvate (PEP); carboxylation of PEP gives rise to oxaloacetate. Oxaloacetate appears to be metabolized to 2-oxoglutarate as in the TCA cycle [see Appendix II(a)] – via citrate in Methanosarcina barkeri, via malate in Methanobacterium thermoautotrophicum. Some species (e.g. Methanococcus thermolithotrophicus, Methanosarcina barkeri ) can carry out NITROGEN FIXATION [Nature (1984) 312 284–288; FEMS Ecol. (1985) 31 47–55]. methanogenesis The biosynthesis of methane (CH4 ): an energyyielding process carried out by certain members of the domain Archaea (METHANOGENS) in anaerobic environments that are characterized by an Eh below about
330 mV (see e.g. ANAEROBIC DIGESTION, RUMEN and WETWOOD). Methane can be formed from several substrates: carbon dioxide and hydrogen (or carbon dioxide and formate), acetate, methanol, or methylamines. Methanogenesis involves a number of novel enzymes and coenzymes/cofactors [FEMS Reviews (1999) 23 13–38]. Methane from carbon dioxide and hydrogen. Essentially, the carbon atom of carbon dioxide is bound, sequentially, to each of several C1 -carrier molecules and undergoes progressive reduction (via formyl and methyl stages) to methane (see figure). The final stage (reduction of CoM-S-CH3 ) is thermodynamically 0 favourable (1G0 greater than
100 kJ). Methane from acetate. Growth on acetate is slower than that on carbon dioxide and hydrogen; the free energy of the reaction CH3 CO2
C H2 O

! CH4 C HCO3
is about
37 kJ. Note that this pathway differs from the carbon dioxide/hydrogen pathway e.g. in the requirement for an initial stage of ATP-dependent activation. Methanogenesis from acetate is inhibited by cyanide (which inhibits CO dehydrogenase). Methane from methanol. In this pathway, the methyl group from one molecule of methanol is oxidized to provide electrons 468

METHANOGENESIS. Two major pathways in the biosynthesis of methane: (i) synthesis from carbon dioxide, and (ii) synthesis from acetate. (Methanol and methylamines are alternative substrates.) The final stage of biosynthesis, i.e. reduction of methyl-coenzyme M (see later), is common to all the methane-forming pathways. (i) Methane from carbon dioxide. In this pathway, the reduction of carbon dioxide can be linked to the oxidation of either hydrogen or formate; the reactions shown occur in both hydrogen- and formate-oxidizing pathways. Initially, carbon dioxide is reduced to a formyl residue on the coenzyme methanofuran (MFR; earlier name: carbon dioxide reduction factor, CDR factor). Methanofuran is a long-chain molecule containing an aromatic ring and a terminal furan ring. This initial reduction is catalysed by formylmethanofuran dehydrogenase. The formyl group is then transferred to tetrahydromethanopterin (THMP). Part of the THMP molecule resembles FOLIC ACID, but the molecule is much larger than that of folic acid and it includes a sugar residue. The conversion of 5-formyl-THMP to 5,10-methenyl-THMPC is catalysed by the enzyme N5 , N10 -methenyltetrahydromethanopterin cyclohydrolase. Subsequent reductions in some methanogens (e.g. strains of Methanosarcina barkeri) involve an enzyme acting in association with coenzyme F420 (factor 420), a 5-deazaflavin derivative that serves as an electron carrier. Strains of e.g. Methanococcus thermolithotrophicus use an F420 -independent dehydrogenase to convert 5,10-methenyl-THMPC to 5,10-methylene-THMP. Finally, the methyl group is transferred from THMP to coenzyme M (CoM-SH; 2-mercaptoethanesulphonic acid; HS(CH2 )2 SO3
) in preparation for its reduction to methane by the enzyme methyl-coenzyme M reductase; in all cases, the electron donor for this reduction is coenzyme B (CoB; 7-mercaptoheptanoylthreonine phosphate). In the reductases from Methanobacterium thermoautotrophicum the active site of the enzyme contains two molecules of coenzyme F430 (factor 430), a nickel-containing porphinoid. Reduction of CoM-S-S-CoB regenerates the two coenzymes. (ii) Methane from acetate. The sequence of reactions shown are those for Methanosarcina thermophila; the pathway differs slightly in some methanogens. (Continued on page 470.)

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Methanogenium for the reduction of methyl groups from (three) other molecules of methanol, the products being methane, carbon dioxide and water. For methane synthesis, methyl groups must be bound to coenzyme M in preparation for methanogenic reduction involving CoB-SH (see figure). Contributing to this pathway in Methanosarcina barkeri is an enzyme system that includes methanol:corrinoid methyltransferase which catalyses the initial transfer of methyl groups to the corrinoid moiety; further enzymic activity transfers the methyl groups to CoM-SH. In nature, methanogens are believed to produce most of the methane from acetate; in vitro studies on the degradation of rice straw in anoxic paddy soil have indeed shown that a high proportion of methane is synthesized from acetate under those conditions [FEMS Ecol. (2000) 31 153–161]. Earlier work had suggested that acetate may be the preferred substrate at 10° C, with hydrogen being used at higher temperatures [FEMS Ecol. (1997) 22 145–153]. However, despite the overall picture, in certain locations the contribution of hydrogen to methanogenesis may be ¾70–100% [FEMS Ecol. (1999) 28 193–202]. The production of methane in anoxic soils can be suppressed e.g. by nitrate; such inhibition appears to be due to the effects of intermediates of the denitrification process [FEMS Ecol. (1999) 28 49–61]. Methanogenium A genus of archaeans of the family METHANOMICROBIACEAE. Cells: cocci in which the cell wall consists of an S LAYER only; the GRAM REACTION is negative. Species include M. cariaci and M. marisnigri, both peritrichously flagellated organisms with an optimum growth temperature of ca. 20° C. methanol utilization See METHYLOTROPHY. Methanolobus A genus of METHANOGENS (see METHANOSARCINACEAE). The cells of M. tindarius are monoflagellated cocci (ca. 1 µm diam.); the cell wall consists of an S LAYER only. Methanol and methylamine are methanogenic substrates. GC%: ca. 46. Methanomicrobiaceae A family of METHANOGENS (order METHANOMICROBIALES); genera: METHANOGENIUM, METHANOMICROBIUM, METHANOSPIRILLUM. Methanomicrobiales An order of METHANOGENS comprising the families METHANOMICROBIACEAE, METHANOPLANACEAE and METHANOSARCINACEAE. Methanomicrobium A genus of archaeans of the family METHANOMICROBIACEAE. Cells: typically short rods in which the cell wall consists of an S LAYER only; the GRAM REACTION is negative. M. mobile. Polarly flagellated rods which need e.g. acetate, THIAMINE, PYRIDOXINE and PABA for growth. Habitat: RUMEN. M. paynteri. Non-motile coccobacilli which occur in marine sediments. Methanoplanaceae A family of METHANOGENS (order METHANOMICROBIALES) [validation: IJSB (1984) 34 270]. One genus: METHANOPLANUS.

A genus of archaeans of the family METHThe cells of M. limicola, the sole species, are plate-like and are bounded by an S LAYER; this organism has strong affinities with Methanogenium spp [Book ref. 157, p 17]. Methanosaeta A genus of obligately acetotrophic METHANOGENS (methanogens which synthesize methane only from acetate). The organisms, which include M. concilii and M. thermoacetophila, are found e.g. in rice fields. Methanosarcina A genus of archaeans of the family METHANOSARCINACEAE. Cells: non-motile, coccoid to irregularly shaped forms, ca. 1–3 µm; the heteropolysaccharide-containing cell wall is a thick (up to ca. 200 nm) layer which may be laminated at the periphery. GAS VACUOLES are found in some strains. The original type species, M. methanica, has been rejected and replaced by M. barkeri [IJSB (1986) 36 492]. M. acetivorans. An acetotrophic marine species [AEM (1984) 47 971–978]. M. barkeri. Cells grow as aggregates. Most strains can produce methane from carbon dioxide and hydrogen, acetate, methanol or methylamine. Strain FR-19 lyses spontaneously in substrate-depleted media [JGM (1985) 131 1481–1486]. M. mazei (cf. METHANOCOCCUS) is similar to M. barkeri but differs e.g. in that M. mazei metabolizes acetate and methanol readily but carbon dioxide and hydrogen poorly or not at all. Methanosarcinaceae A family of METHANOGENS (order METHANOMICROBIALES). Depending on species or strain, some or all of the following substrates are used for METHANOGENESIS: acetate, CO2 C H2 , methanol, methylamines. Genera: METHANOSARCINA, METHANOTHRIX; it has been proposed that the genera METHANOCOCCOIDES and METHANOLOBUS be incorporated in the family [IJSB (1984) 34 444–450]. Methanospirillum A genus of archaeans of the family METHANOMICROBIACEAE. M. hungatei is a facultative autotroph which occurs in sewage sludge; the cells are curved, sheathed rods or filaments that are lophotrichously flagellated. Methanothermaceae A family of archaeans of the order METHANOBACTERIALES. One genus: METHANOTHERMUS. Methanothermus A genus of archaeans (family METHANOTHERMACEAE) in which the cell wall consists of two layers: a PSEUDOMUREIN-containing layer and an (outermost) S LAYER. Thermophilic (optimum: 83° C). M. fervidus. Cells: non-motile rods, ca. 0.4 ð 1–3 µm; the GRAM REACTION is positive. Methane is formed from carbon dioxide and hydrogen but not from formate; yeast extract is needed for growth. GC%: ca. 33. Methanothrix A genus of archaeans of the family METHANOSARCINACEAE. M. soehngenii is common in anaerobic digestors; cells: rods, ca. 0.8 ð 2 µm, or long, sheathed filaments – each filament often consisting of several hundred rods. The GRAM REACTION is negative. Methane is formed from acetate but not from carbon dioxide and hydrogen or from formate, methanol or methylamine. Methanoplanus

ANOPLANACEAE.

METHANOGENESIS (continued) Initially, acetate undergoes ATP-dependent activation to acetyl-CoA – catalysed by the two enzymes acetate kinase and phosphotransacetylase. (In Methanosaeta, this section of the pathway differs in that the formation of acetyl-CoA is catalysed by acetate thiokinase.) The methyl group is then transferred to tetrahydrosarcinapterin (THSP; analogous to THMP, above) by an enzyme complex that includes CO dehydrogenase and CoA synthase; the activity of these enzymes results in the cleavage of carbon–carbon and carbon–sulphur bonds – and also oxidation of the carbonyl group (from acetyl-CoA) to carbon dioxide. Electrons derived from oxidation of the carbonyl group are involved in the final methanogenic reduction of the methyl group after the latter has been transferred to coenzyme M. In Methanosarcina thermophila the cam gene encodes a CARBONIC ANHYDRASE which apparently includes a signal peptide (see SIGNAL HYPOTHESIS); it has been suggested that, by hydrating carbon dioxide in the periplasm, this enzyme may facilitate removal of carbon dioxide from the cytoplasm – and may thus promote conditions thermodynamically more favourable for methanogenesis.

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methylene blue MAP belongs to a diverse family of physiologically important aminopeptidases [bacterial aminopeptidases: FEMS Reviews (1996) 18 319–344]. L-methionine biosynthesis See Appendix IV(d). (See also MICROCINS.) methionine deformylase In bacteria: an enzyme which cleaves the formyl group from methionine at the N-terminal of a newly synthesized protein. L-methionine-DL-sulphoximine See MSX. methisazone See ISATIN-b-THIOSEMICARBAZONE. Methocel See METHYLCELLULOSE. methotrexate See FOLIC ACID ANTAGONIST. methoxatin See QUINOPROTEIN. methoxsalen 8-MethylPSORALEN. methoxyamine (as a mutagen) See HYDROXYLAMINE. 6-methoxymellein A PHYTOALEXIN elicited from the carrot plant e.g. by cupric or mercuric chloride. methyl-accepting chemotaxis protein See CHEMOTAXIS. methyl blue (cotton blue) A blue acid TRIPHENYLMETHANE DYE; cf. LACTOPHENOL COTTON BLUE. methyl bromide (CH3 Br) Methyl bromide vapour is fungicidal, insecticidal and herbicidal; it has good powers of penetration and is used as a fumigant. methyl green A green basic TRIPHENYLMETHANE DYE. (See also METHYL GREEN–PYRONIN STAIN.) methyl green–pyronin stain (Unna–Pappenheim stain) A stain which can distinguish DNA (which stains green) from RNA (which stains red); it can be used e.g. to distinguish lymphocytes from (ribosome-rich) plasma cells. methyl orange A PH INDICATOR: pH 3.0–4.4 (red to orangeyellow); pKa 3.6. methyl red A PH INDICATOR: pH 4.4–6.2 (red to yellow); pKa 5.1. methyl red test (MR test) An IMVIC TEST which determines the ability of an organism to acidify a phosphate-buffered glucose–peptone medium to pH 4.4 or below. The medium is inoculated and incubated for 48 h at 37° C or 5 days at 30° C. Two drops of METHYL RED solution (0.02% w/v in ca. 50% ethanol) are added to the culture; a red coloration indicates a positive reaction. (N.B. Too short an incubation time may give a false-positive reaction: some organisms (e.g. Klebsiella pneumoniae subsp. pneumoniae) initially form acidic metabolic products which are later metabolized further.) The VOGES–PROSKAUER TEST can be performed after the MR test using the same culture. methyl violet A composite TRIPHENYLMETHANE DYE which includes crystal violet and 4,40 -bis(dimethylamino)-400 -(methylamino) triphenylmethyl chloride. methyl viologen (Paraquat) 1,10 -Dimethyl-4,40 -dipyridinium, a widely used herbicide. (See also PHOTOSYNTHESIS.) The reduced form of methyl viologen is used e.g. as a reducing agent in laboratory studies. 3-methyladenine-DNA glycosylase I See EXCISION REPAIR. 3-methyladenine-DNA glycosylase II See ADAPTIVE RESPONSE. methylation (of DNA) See DNA METHYLATION. methylcellulose (Methocel) An unbranched polymer (MWt ca. 143000) used e.g. to increase the viscosity of a medium in order to slow down rapidly motile organisms – see COUNTING METHODS. (cf. FICOLL.) methylcobalamin See VITAMIN B12 . methylene blue A blue basic thiazine DYE used e.g. in STAINING and VITAL STAINING and as a redox indicator (E0 D C11 mV at pH 7). (See also e.g. METHYLENE BLUE TEST; TOXOPLASMA DYE TEST.) Leuco methylene blue is the reduced (colourless) form of methylene blue. Loeffler’s methylene blue is

M. concilii is an acetotrophic species isolated from sewage sludge [CJM (1984) 30 1383–1396]. [Acetate and carbon dioxide assimilation by M. concilii : JB (1985) 162 905–908.] methanotroph Any organism capable of METHANOTROPHY. methanotrophy The use of methane as the sole source of carbon and energy: a mode of metabolism which occurs under aerobic and microaerobic conditions in certain bacteria (see e.g. METHYLOCOCCACEAE). (cf. METHYLOTROPHY.) Most methanotrophic bacteria are obligately methanotrophic; these organisms include species of Methylococcus and Methylomonas. The methanotrophic bacteria occur e.g. in soil, water and sediments. The oxidation of methane by methanotrophs significantly affects the global methane budget in that much less methane reaches the atmosphere; this reduces the contribution of methane to global warming. In members of the Methylococcaceae, methane is initially oxidized to methanol by METHANE MONOOXYGENASE (q.v.); the subsequent oxidations are: methanol ! formaldehyde ! formate ! carbon dioxide. When methane is used as the sole source of carbon and energy, some formaldehyde is assimilated into cell biomass while the remainder is oxidized to yield energy. [Methane oxidation in natural waters: AEM (1982) 44 435– 446. Methane oxidation by microorganisms: Book ref. 132, pp 173–200. Methanotrophic bacteria (review): MR (1996) 60 439–471. Ecology of methanotrophic species studied by molecular methods: FEMS Ecol. (1998) 27 103–114. Detection and classification of atmospheric methane-oxidizing bacteria in soil: Nature (2000) 405 175–178.] methazotrophic Refers to any organism capable of using methylamines as the sole source of nitrogen (but not as sole source of carbon and energy); methazotrophs include various yeasts, e.g. Candida utilis. [Oxidation of methylamines by yeasts: Book ref. 169, pp. 155–164.] methenamine See HEXAMINE. methenamine–silver stain (Grocott–Gomori stain; Gomori stain) A stain used e.g. for detecting actinomycetes or fungi in tissue sections. The section is oxidized in 5% chromic acid for 1 h, washed in tap water, washed for 1 min in 1% sodium bisulphite to eliminate chromic acid, and washed for 10 min in tap water. After 3–4 changes of distilled water the section is immersed in a solution made by adding 0.4% aqueous borax (108 ml) to a mixture of 10% silver nitrate (7 ml) and 3% methenamine (100 ml); the temperature is kept at 58–60° C until the section becomes yellow-brown (30–60 min). The slide is rinsed repeatedly in distilled water, washed for 2–5 min in 2% sodium thiosulphate to remove unreduced silver, washed in tap water, and counterstained for ca. 1 min in a solution of light green (0.04% w/v) containing 0.04% v/v glacial acetic acid. Mycelium stains brown-black, tissues green. methicillin See PENICILLINS. methicillin-resistant Staphylococcus aureus See MRSA. methicillinase See MRSA. methionine aminopeptidase (MAP) In bacteria: an enzyme required for excision of the N-terminal methionine of a newly synthesized protein. In e.g. Escherichia coli, the N-terminal methionine is cleaved from about 50% of proteins. Whether or not such cleavage occurs in a given protein is influenced by the identity of the penultimate N-terminal amino acid; cleavage, or otherwise, of the N-terminal methionine thus determines the identity of the N-terminal amino acid in the mature protein, and, in this way, influences the protein’s half-life (according to the N-END RULE). 471

methylene blue test prepared by adding 0.01% KOH (100 ml) to 1% methylene blue in 95% ethanol (30 ml). If allowed to ‘ripen’ (i.e. oxidize slowly) over several months this stain becomes polychrome methylene blue: a mixture of methylene blue and certain products of its spontaneous oxidation (e.g. the metachromatic dyes azure A and azure B).

Methylocaldum A genus of methylotrophic bacteria classified within the (gamma) PROTEOBACTERIA. Methylococcaceae A family of Gram-negative, obligately methylotrophic bacteria characterized by the ability to use methane as the sole source of carbon and energy under aerobic or microaerobic conditions (see METHANOTROPHY); bacteria which can use other C1 compounds, but not methane, are excluded. Two genera: METHYLOCOCCUS and METHYLOMONAS. [Book ref. 22, pp. 256–261.] (cf. METHYLOMONADACEAE.) Members of the Methylococcaceae occur e.g. in soil and in water overlaying anaerobic mud. The cells range from cocci to rods, and all contain a complex arrangement of intracytoplasmic membranes when grown on methane; some strains are motile (polarly flagellated). Pigments, some water-soluble, are formed by some strains and may be e.g. blue, brown, red or yellow. Certain strains form desiccation-resistant resting stages; these stages may be cysts (similar to those of Azotobacter spp), ‘lipid cysts’ (which contain PHB inclusions, lack intracellular membranes, and have a thick pericellular coating), or ‘exospores’ (which develop by polar budding, and which are resistant to 85° C/15 min). Metabolism is respiratory (oxidative) with oxygen as the terminal electron acceptor; cytochromes of the a, b, c and o types occur in those strains examined. According to strain, the TCA CYCLE may be complete or e.g. may lack 2-oxoglutarate dehydrogenase (in which case the pathway is primarily biosynthetic). All strains can use methanol as a sole source of carbon and energy, and many or all can use formaldehyde. Methane oxidizers can use other carbon compounds, simultaneously with methane, as co-oxidizable substrates to provide carbon and energy; such supplementary carbon and energy sources include e.g. acetate, alkanes, formate, primary alcohols, and various alicyclic, aromatic and heterocyclic compounds. At least one species, Methylococcus capsulatus, can fix CO2 via the Calvin cycle, and some methanotrophs can carry out NITROGEN FIXATION [JGM (1983) 129 3481–3486]. All strains which have been examined are catalase Cve and oxidase Cve. Aerobic methane-oxidizing bacteria were divided into two major physiological groups; these groups included species which were not formally included in the Methylococcaceae. Type I organisms (e.g. Methylococcus capsulatus, Methylomonas methanica) form intracytoplasmic membranes comprising bundles of vesicular discs, may form cysts, have an incomplete TCA cycle, and assimilate carbon by the RMP PATHWAY. Type II organisms (e.g. METHYLOBACTERIUM, METHYLOSINUS TRICHOSPORIUM) form paired intracytoplasmic membranes aligned with the cell periphery, may form ‘lipid cysts’ or ‘exospores’, have a complete TCA cycle, and assimilate carbon by the SERINE PATHWAY. [Ecology, isolation and culture: Book ref. 45, pp. 894–902.] Methylococcus A genus of Gram-negative bacteria (family METHYLOCOCCACEAE) which occur e.g. in mud, soil and water. Cells: non-pigmented, non-motile cocci, ca. 1 µm in diameter. The organisms may be cultured on e.g. nitrate–mineral salts media with a gaseous phase consisting of a 30:70 mixture of methane and air; growth occurs between 30 and 50° C (optimally at 37° C), enrichment and primary isolation being carried out at 45° C. GC%: ca. 62.5. Type species: M. capsulatus. Methylomonadaceae An obsolete bacterial family which consisted of methylotrophic organisms – the use of methane not being an obligatory requirement. (cf. METHYLOCOCCACEAE.) Methylomonas A genus of Gram-negative bacteria within the family METHYLOCOCCACEAE. Cells: straight or curved, sometimes branched, motile (polarly flagellated) rods, 0.5–1.0 ð 1.0–4.0 µm. Growth occurs optimally at 30° C, no growth

METHYLENE BLUE

As a redox indicator (see e.g. GASPAK and REDOX POTENTIAL), methylene blue is often used in a TRIS- or phosphate-buffered solution at pH 9; at pH 9 the dye becomes colourless at a lower Eh than it does at pH 7. methylene blue test (for milk) A test used to assess the numbers of (certain types of) microorganisms in untreated or pasteurized MILK. To a standard volume of milk is added a fixed volume of a solution of METHYLENE BLUE (or methylene blue thiocyanate); the whole is incubated at 37° C and examined periodically. If the milk contains large numbers of organisms that are metabolically active at 37° C, the dye will be quickly reduced to the colourless leuco form; decolorization is delayed if the milk contains relatively few organisms. The time taken for dye decolorization is thus a guide to the microbial load. (cf. RESAZURIN TEST.) methylglyoxal bypass A sequence of reactions which can bypass reactions of the EMBDEN–MEYERHOF–PARNAS PATHWAY between triose phosphates and pyruvate. Methylglyoxal synthase converts dihydroxyacetone phosphate to methylglyoxal (2-oxopropanal: CH3 .CO.CHO) and inorganic phosphate; methylglyoxal can then be converted to D-lactate (by two glutathione-dependent enzymes, glyoxalase I and glyoxalase II), or to pyruvate (by methylglyoxal dehydrogenase). Although these enzymes have been identified in various bacteria and yeasts, their significance in vivo remains unclear; they could allow the formation of pyruvate (and hence acetyl-CoA) under conditions of phosphate deficiency which would otherwise limit the formation of 1,3bisphosphoglycerate from glyceraldehyde 3-phosphate. Methylglyoxal is cytotoxic, apparently reacting with 7-methylguanosine in rRNA and thereby inhibiting ribosomal function; the glyoxalase system probably plays an important role in detoxifying methylglyoxal formed from dihydroxyacetone phosphate or during other metabolic processes (e.g. the catabolism of certain amino acids). [Methylglyoxal metabolism: ARM (1984) 38 49–68.] 2-methylisoborneol A substance which is produced by certain aquatic actinomycetes and cyanobacteria (e.g. Lyngbya); in concentrated form, 2-methylisoborneol has a camphor-like smell, but when diluted it has a ‘musty’ or ‘earthy’ odour which can taint WATER SUPPLIES and fish living in the water. (cf. GEOSMIN.) methylmethane sulphonate See ALKYLATING AGENTS. N-methyl-N ′ -nitro-N-nitrosoguanidine See MNNG. N-methyl-N-nitrosourea See ALKYLATING AGENTS. Methylobacterium A genus of facultatively methylotrophic and methanotrophic, rod-shaped bacteria which can alternatively use glucose and other complex substrates as sole sources of carbon and energy. Type species: M. organophilum. (See also METHYLOCOCCACEAE and PROTOMONAS.) 472

metronidazole occurring at 37° C; enrichment and primary isolation are otherwise as described under METHYLOCOCCUS. A pink pellicle is formed at 30° C; colonies are pink or yellow, consistently pink on subculture. A blue diffusible pigment may be formed in iron-deficient media. GC%: ca. 52. Type species: M. methanica. (‘M. methanitrificans’ and ‘M. methanooxidans’ may be synonyms of Methylosinus trichosporium.) Methylophaga A proposed genus of marine methylotrophic bacteria. The organisms are Gram-negative, strictly aerobic rods which grow on methanol, methylamine(s) or fructose (but not methane) and which require vitamin B12 ; those strains tested use the RMP pathway for carbon assimilation. Two species: M. marina, M. thalassia. [IJSB (1985) 35 131–139.] Methylophilus methylotrophus A species of obligately methylotrophic, non-methanotrophic bacteria (see METHYLOTROPHY) which assimilate carbon via the RMP pathway and which have been used in the production of SINGLE-CELL PROTEIN. Methylosinus trichosporium A species of methanotrophic, obligately methylotrophic, typically rod-shaped or vibrioid bacteria (see METHANOTROPHY, METHANE MONOOXYGENASE, METHYLOCOCCACEAE). [Effect of growth conditions on intracytoplasmic membranes and MMO activity: JGM (1981) 125 63–84.] methylotroph Any organism capable of METHYLOTROPHY. methylotrophy Oxidative metabolism characterized by (i) obligate or facultative use of C1 COMPOUNDS as the sole source of carbon and energy, and (ii) assimilation of formaldehyde (produced during methylotrophic metabolism) as a major source of carbon. Methylotrophy includes METHANOTROPHY. Methylotrophic organisms include certain bacteria (e.g. Hyphomicrobium, Methylobacterium spp, members of the family METHYLOCOCCACEAE, Methylophaga spp, Methylophilus methylotrophus, Microcyclus and Paracoccus denitrificans) and some fungi (e.g. species of Candida, Hansenula and Pichia). (cf. CARBOXYDOBACTERIA.) (a) Methylotrophy in bacteria. Most of the C1 compounds can be oxidized via a sequence of reactions which end in HCHO ! HCOOH ! CO2 . Formaldehyde may be assimilated by either the RMP PATHWAY or the SERINE PATHWAY, according to species. (The serine pathway also assimilates some carbon dioxide.) Energy may be derived from direct (non-cyclical) oxidative pathways (e.g. methanol ! formaldehyde ! formate ! carbon dioxide) or from the (cyclical) RMP PATHWAY operating in a dissimilatory mode. The TCA cycle appears to play little or no part in the generation of energy from C1 substrates. Methanol is used by most methylotrophs. It is oxidized to formaldehyde by a QUINOPROTEIN: methanol dehydrogenase (MDH; EC 1.1.99.8), whose electron acceptor is a soluble form of cytochrome cL . [Roles for c cytochromes in methylotrophs: JGM (1984) 130 3319–3325.] Methane is oxidized to formaldehyde via methanol (see METHANOTROPHY). Methylamines are oxidized directly to formaldehyde in reactions that usually involve dehydrogenases or monooxygenases; electrons from these substrates may be transferred to cyt b (via a flavoprotein), or may be passed to cyt c via the ‘blue protein’ amicyanin. The oxidation of formaldehyde to formate may be catalysed by various enzymes – e.g. (i) MDH; (ii) NAD- and reduced-glutathione-dependent formaldehyde dehydrogenase (EC 1.2.1.1); or (iii) NAD(P)-independent non-specific aldehyde dehydrogenase. Formate is oxidized by NAD-dependent formate dehydrogenase (EC 1.2.1.2). (Some methylotrophs can use exogenous formate as a source of energy and carbon.)

[Formaldehyde metabolism: Book ref. 169, pp 315–323. Physiology and biochemistry of methylotrophic bacteria: AvL (1987) 53 23–28. Energetics of bacterial metabolism of C1 compounds: AvL (1987) 53 37–45.] (b) Methylotrophy in fungi. Of C1 compounds, only methanol has been studied extensively (as a substrate for certain yeasts); however, other C1 compounds have been reported to be used as substrates by fungi. The assimilatory and energy-yielding pathways of methanol metabolism in yeasts differ from those in bacteria. Methanol can be oxidized via the sequence: methanol ! formaldehyde ! formate ! carbon dioxide. The oxidation of methanol to formaldehyde takes place within PEROXISOMES and is catalysed by ‘methanol oxidase’ (EC 1.1.3.13), a non-specific alcohol oxidase which can oxidize e.g. several alkanols and alkenols, and which consists of eight FAD-containing subunits. The oxidation of methanol yields hydrogen peroxide as well as formaldehyde; CATALASE, within the peroxisome, eliminates the peroxide (as water and oxygen). Formaldehyde may be assimilated, via the XMP PATHWAY, or may be oxidized to yield energy. The oxidation of formaldehyde occurs within the cytoplasm. In Candida boidinii this reaction appears to occur in three stages, the first stage involving NADC - and GSH-linked (reduced-glutathione-linked) formaldehyde dehydrogenase (EC 1.2.1.1): GSH C HCHO C NADC

! HCO-SG C NADH C HC HCO-SG (S-formylglutathione) is hydrolysed by S-formylglutathione hydrolase (EC 3.1.2.12): HCO-SG C H2 O

! GSH C HCOOH Finally, HCOOH may be oxidized to carbon dioxide by NADlinked formate dehydrogenase – although the low substrate affinity of this enzyme in cell-free systems has raised doubts as to its function in vivo. Methylotrophy has also been recorded in the yeast Hansenula polymorpha. NADH generated in methanol-grown yeasts is oxidized in a (ROTENONE-insensitive but cyanide-sensitive) reaction involving an NADH dehydrogenase located at the outer surface of the inner mitochondrial membrane – the maximum energy yield being 2 ATP/NADPH. (In e.g. glucose-grown cells, most NADH is generated intra-mitochondrially and is oxidized by an NADH dehydrogenase located at the inner surface of the inner mitochondrial membrane, the maximum yield of energy being 3 ATP/NADH.) [Methylotrophic yeasts: AvL (1987) 53 29–36.] methymycin See MACROLIDE ANTIBIOTICS. metiram An agricultural antifungal agent used e.g. for the control of late blight of potato; it is a complex of ZINEB and polyethylene THIURAM DISULPHIDE. Metopus See HETEROTRICHIDA. metritis Inflammation of the uterus. (cf. ENDOMETRITIS; see also CONTAGIOUS EQUINE METRITIS.) Metrizamide See IODINATED DENSITY-GRADIENT MEDIA. metrocyte See SARCOCYSTIS. metronidazole (Flagyl) 1-(2-Hydroxyethyl)-2-methyl-5-nitroimidazole: a NITROIMIDAZOLE antimicrobial agent used to treat e.g. amoebic and balantidial DYSENTERY, GIARDIASIS, genitourinary TRICHOMONIASIS and infections caused by anaerobic bacteria, e.g. PSEUDOMEMBRANOUS COLITIS and VINCENT’S ANGINA. The bactericidal effect of metronidazole on Helicobacter pylori appears to depend on the reduced (active) 473

Metschnikowia Mickle shaker An apparatus used e.g. for the ballistic disintegration of tissue or cells; in principle it resembles the BRAUN MSK TISSUE DISINTEGRATOR. (See also BALLOTINI, CELL DISRUPTION and ULTRASONICATION.) miconazole (1-[2,4-dichloro-b-(2,4-dichlorobenzyloxyl)phenethylimidazole]) An AZOLE ANTIFUNGAL AGENT with a broad spectrum of antifungal activity; it also has activity against certain bacteria (particularly Gram-positive species) and e.g. against Naegleria fowleri. Miconazole is used mainly in the treatment of superficial mycoses; it is usually administered topically, but can be given intravenously (in cases of invasive or systemic mycosis) or orally (e.g. to reduce intestinal populations of Candida spp). Micrasterias A genus of placoderm DESMIDS. microaerobic Refers to an environment in which oxygen is present (cf. ANAEROBIC) but at a partial pressure which is (usually significantly) lower than that in air. microaerophilic Refers to any organism which grows optimally in a MICROAEROBIC environment. (Frequently the term is also used as a synonym of microaerobic.) microalgae Microscopic algae – particularly unicellular algae such as CHLAMYDOMONAS, CHLORELLA, DIATOMS, etc. microarray (DNA) See DNA CHIP. Microascales An order of fungi of the ASCOMYCOTINA; the organisms are primarily saprotrophs in soil and dung, but some can be pathogenic in man and other animals. Ascocarp: perithecioid or cleistothecioid, dark and solitary, sometimes setose; hamathecium: absent. Asci: rounded, thin-walled, evanescent. Ascospores: aseptate, pigmented. Genera: e.g. Microascus, PSEUDALLESCHERIA. Microascus See MICROASCALES. Microbacterium A genus of catalase-positive, asporogenous bacteria (order ACTINOMYCETALES, wall type VI – see also PEPTIDOGLYCAN) which frequently occur in dairy products (e.g. spraydried milk, some cheeses) – presumably as a result of improper cleansing of dairy equipment. In culture the organisms are slender, pleomorphic, non-motile rods. Growth occurs optimally at ca. 30° C on e.g. media containing yeast extract, peptone and milk; L-(C)-lactic acid is formed from glucose. Some strains produce a yellowish pigment. All strains grow aerobically. The organisms are typically thermoduric, surviving e.g. 63° C/30 min and 72° C/15 min. GC%: ca. 69–70. Type species: M. lacticum. (For M. thermosphactum see BROCHOTHRIX.) microbe Syn. MICROORGANISM. microbial insecticides See BIOLOGICAL CONTROL. microbial leaching (of ores) See LEACHING. microbial mat A complex, benthic microbial community which forms a cohesive layer and which is typically dominated by CYANOBACTERIA or other photosynthetic prokaryotes – and occasionally e.g. by microalgae; microbial mats occur in those regions where environmental stress tends to exclude, or reduce the numbers of, metazoans – e.g. in intertidal and hypersaline regions, in hot springs, and around HYDROTHERMAL VENTS. Microorganisms which occur in microbial mats include e.g. species of Lyngbya and Microcoleus, various purple photosynthetic bacteria, Chloroflexus, and certain aerobic and anaerobic chemotrophs, including SULPHATE-REDUCING BACTERIA. Microbial mats are believed to have given rise to STROMATOLITES, and, under certain conditions, may have been precursor material for KEROGEN and hydrocarbon deposits; in the latter context it has been suggested that oil is more likely to have been derived from marine organic deposits than from terrestrial plant material which, under appropriate conditions, gives rise to coal. [Book ref. 154.]

form of the drug rather than on toxic oxygen radicals formed during its reduction [JAC (1998) 41 67–75]. Metschnikowia A genus of unicellular and pseudomycelial fungi (family METSCHNIKOWIACEAE) in which multilateral budding occurs. Ascospores: acicular, 1–2 per ascus. Six species are recognized; they occur in aquatic and terrestrial habitats and as parasites in invertebrates. M. pulcherrima and M. reukaufii are teleomorphs of Candida pulcherrima and Candida reukaufii, respectively. [Book ref. 100, pp. 266–278.] Metschnikowiaceae (Nematosporaceae; Spermophthoraceae) A family of fungi (order ENDOMYCETALES) which includes unicellular, pseudomycelial and mycelial forms. Ascospores: fusiform to acicular (cf. SACCHAROMYCETACEAE). Genera include e.g. Ashbya, COCCIDIASCUS, Eremothecium, METSCHNIKOWIA, NEMATOSPORA, Spermophthora. Members are generally parasitic in plants and/or invertebrates (see e.g. STIGMATOMYCOSIS). Species of Ashbya and Eremothecium are important commercial sources of riboflavin. metula In the conidiophores of certain fungi: a cell, or a short extension or branch (or part of a branch), which bears one or more phialides (see CONIDIUM) at its apex – see e.g. ASPERGILLUS and PENICILLIUM. Mexico virus A SMALL ROUND STRUCTURED VIRUS. mezlocillin See PENICILLINS. MF0 F1 H+ -ATPase See PROTON ATPASE. MFP See MEMBRANE FUSION PROTEIN. MFS Major facilitator superfamily: a category of TRANSPORT SYSTEMS which occur in prokaryotes and eukaryotes; they include pmf-dependent efflux pumps which mediate extrusion of antibiotics – and which therefore confer resistance to particular antibiotic(s). Examples of MFS systems are the various efflux pumps in Gram-negative bacteria which confer resistance to tetracyclines. Each pump encoded by a tetA gene is an integral inner membrane protein containing multiple transmembrane helices; tetA genes have been found on transposons and plasmids. MG fungus See APHANOMYCES. MGIT 960 A fully automated BACTEC system (Becton Dickinson) (MGIT D mycobacteria growth indicator tube) used e.g. for detecting Mycobacterium tuberculosis [evaluation: JCM (1999) 37 748–752]. MHA (immunol.) Major histocompatibility antigen. MHA-TP test Microhaemagglutination assay for Treponema pallidum antibodies, a miniaturized form of the TPHA TEST. MHC (immunol.) MAJOR HISTOCOMPATIBILITY COMPLEX. MHC restriction Syn. HISTOCOMPATIBILITY RESTRICTION. MHD (1) (serol.) Minimum haemolytic dose. (a) The smallest quantity of COMPLEMENT needed to lyse completely a fixed quantity of a standardized suspension of sensitized erythrocytes. (See also HAEMOLYTIC SYSTEM.) (b) The smallest quantity of a complement-dependent haemolysin needed to lyse completely a fixed quantity of erythrocytes in the presence of excess complement. (c) The smallest quantity of streptolysin O needed to lyse completely a fixed quantity of erythrocytes in the ANTISTREPTOLYSIN O TEST. (The MHD may be referred to as ‘1 unit’.) (See also HD50 .) (2) (virol.) Minimum haemagglutinating dose: the smallest quantity of a haemagglutinating virus capable of bringing about maximum agglutination of the erythrocytes in a given volume of a standardized suspension. mi-1 gene See POKY MUTANT. MIC (of an antibiotic) Minimum inhibitory concentration: the lowest concentration of a given antibiotic which inhibits a given type of microorganism under given conditions. (See also E TEST.) 474

microcomplement fixation microbicidal Able to kill at least some types of microorganism. (cf. MICROBISTATIC.) microbiocoenosis A natural community of microorganisms (including algae, bacteria and protozoa) characterized by phases of short-lived stability. microbiological safety cabinet Syn. SAFETY CABINET. microbiology The study of MICROORGANISMS and their interactions with other organisms and the environment (cf. CELLULAR MICROBIOLOGY). There is considerable overlap between microbiology and certain other disciplines: e.g. biochemistry, immunology, molecular biology and PARASITOLOGY. Microbiology is also directly relevant to certain aspects of medicine, veterinary science, agriculture, the food industry (see FOOD MICROBIOLOGY) and various commercial processes (see INDUSTRIAL MICROBIOLOGY) as well as ecology and pollution studies (see e.g. CARBON CYCLE, NITROGEN CYCLE, SULPHUR CYCLE, SEWAGE TREATMENT and WATER SUPPLIES). microbiota Microscopic organisms, particularly those in soil. Microbispora A genus of bacteria (order ACTINOMYCETALES, wall type III; group: maduromycetes) which occur e.g. in soil. The organisms form branched aerial and substrate mycelium, the former (commonly pink) giving rise to pairs of elongated spores; when grown on certain solid media some species (e.g. M. parva) deposit crystals of IODININ in the medium. The GC% of the type species (M. rosea) has been reported to be ca. 74. [Ecology, isolation and cultivation: Book ref. 46, pp. 2103–2117.] microbistatic Able to inhibit the growth and reproduction of at least some types of microorganism. (cf. MICROBICIDAL.) microbody A particle, typically less than 1 µm diam., consisting of a collection of functionally related enzymes enclosed in a membranous sac; microbodies occur in eukaryotic cells: see e.g. GLYCOSOME, GLYOXYSOME, PEROXISOME. [Microbodies in urateutilizing yeasts: AvL (1985) 51 33–43. ‘How proteins get into microbodies’ (review): BBA (1986) 866 179–203.] (cf. HYDROGENOSOME; LYSOSOME.) microcapsule See CAPSULE. microcarrier cell culture A system for culturing eukaryotic cells in which the cells grow to form a confluent layer on the surface of small solid particles suspended in a slowly agitated medium. [Review: AAM (1986) 31 139–179.] (See also TISSUE CULTURE.) microcins A category of low-MWt BACTERIOCINS produced by members of the Enterobacteriaceae and effective e.g. against bacteria of the same family. The microcins differ from COLICINS in their size, and also differ in that their synthesis is not induced by conditions which trigger the SOS SYSTEM. Typically, microcins are synthesized in the stationary phase, and synthesis tends to be repressed in rich media. The typical microcin ranges in size from a single modified amino acid (microcin A15 appears to be a derivative of methionine) to short or medium-sized peptides (up to ¾50 amino acid residues in length). Microcins are characteristically thermostable (e.g. 100° C/30 min), soluble in methanol–water (5:1), and resistant to extremes of pH and to certain proteases. The microcins can be grouped according to their modes of action: type A microcins inhibit certain metabolic pathways, type B microcins inhibit DNA replication etc. For example, the bacteriostatic microcin A15 inhibits homoserine succinyltransferase in the methionine biosynthetic pathway (see Appendix IV(d)). The bactericidal microcin B17 inhibits DNA gyrase and induces the SOS SYSTEM in Escherichia coli K12 [JGM (1986) 132 393–402]. Microcin C7 is a heptapeptide which blocks protein synthesis. (See also COLICIN V.) Plasmids which specify microcins (M plasmids or, preferably, Mcc plasmids) appear not to encode resistance to conventional

antibiotics. Some of these plasmids are conjugative – e.g. that encoding B17 (pMccB17, an IncFII plasmid) and that encoding C7 (pMccC7, an IncX plasmid). Micrococcaceae A family of asporogenous, Gram-positive cocci which includes the genera MICROCOCCUS (the type genus), STAPHYLOCOCCUS and STOMATOCOCCUS. Micrococcus A genus of Gram-positive, aerobic, chemoorganotrophic, asporogenous, catalase-positive, generally non-motile bacteria which have a GC value (see GC%) of ca. 65–75 and which are typically resistant to lysostaphin; the micrococcal cell wall typically contains little or no teichoic acid (cf. TEICHURONIC ACIDS), and the ratio of glycine to lysine in the PEPTIDOGLYCAN is characteristically 30 viruses (including e.g. Punta Toro virus, RIFT VALLEY FEVER virus, Rio Grande virus, Sicilian sandfly fever virus). MWts of L, M and S RNAs: ca. 2.6–2.8, 1.8–2.2, and 0.7–0.8 ð 106 , respectively; MWts of proteins L, G1, G2 and N: ca. 145–200, 55–70, 50–60, and 20–30 ð 103 , respectively. The phlebovirus M RNA appears to resemble that of the bunyaviruses (see BUNYAVIRIDAE) in its genetic organization; however, the S RNA of Punta Toro virus appears to be an AMBISENSE RNA, encoding the NSs protein on a viral-sense subgenomic mRNA and the N protein on a viral-complementary subgenomic mRNA. Phleogena See AURICULARIALES. phlobaphenes See TANNINS. phloem necrosis (of coffee) A disease of the coffee plant (e.g. Coffea liberica, C. arabica) caused by Phytomonas sp. Symptoms: leaves become yellow and fall prematurely, and CALLOSE is deposited in the sieve tubes. Only plants older than ca. two years are affected. Vectors: unknown, but heteropterans are suspected. phloeophagous ‘Bark-eating’ (see e.g. AMBROSIA FUNGI). Phlogiotis See TREMELLALES. phlogistic Able to cause inflammation. phloretin See PHLORIDZIN. phlorhizin Syn. PHLORIDZIN. phloridzin (phlorhizin) A phenolic glycoside formed in certain tissues in apple trees (Malus spp) and in other members of the Rosaceae. The aglycone part of phloridzin, phloretin (b(4-hydroxyphenyl)-propionophlorophenone), can be liberated by b-glycosidases and oxidized by polyphenol oxidase to yield polymers that are toxic to e.g. Venturia inaequalis. PHLS Public Health Laboratory Service, 61 Colindale Avenue, London NW9, United Kingdom. pho regulon (phosphate regulon) In Escherichia coli: a REGULON comprising the pho genes: phosphate-controlled genes whose activity depends on the level of available Pi (inorganic orthophosphate). The cell’s response to Pi starvation is complex and not fully understood, but the following model has been suggested for regulation of the pho genes. Regulation is exerted partly through the products of genes phoR and phoB. PhoR and PhoB are associated in a TWOCOMPONENT REGULATORY SYSTEM in which PhoR is a sensor protein in the cytoplasmic membrane, and PhoB acts as a regulator protein. With low levels of phosphate, PhoR undergoes ATP-dependent autophosphorylation and transfers phosphate to PhoB. PhoB¾P behaves as a transcriptional activator by binding to the so-called phosphate box: a nucleotide sequence associated with the promoters of e.g. the phoA, phoE and phoS genes; PhoA is a periplasmic alkaline PHOSPHATASE (which releases Pi from organic phosphate esters), PhoE is a PORIN (for phosphate uptake), and PhoS is a Pi-binding protein. If phosphate levels rise, PhoB¾P is de-phosphorylated by the joint activity of PhoR and the product of gene phoU; this switches off the pho regulon. Regulation of pho genes appears also to involve element(s) of the pst (phosphate-specific transport) operon because phosphatase (PhoA) is produced constitutively in pst mutants. phoA gene See PHO REGULON. phoB gene See PHO REGULON. phobic response (shock movement; shock reaction; avoiding reaction) A transient behavioural response of a motile organism to a noxious stimulus, where the stimulus is an abrupt change in an external parameter (e.g., a light/dark boundary). The nature of 578

phosphorescence the response depends on the organism, but typically the organism stops and then either reverses or reorientates and proceeds in a new, randomly selected direction. If conditions in the new direction are not significantly better, the phobic response may be repeated until the organism eventually moves into a more favourable region – when smooth swimming tends to supervene; thus, repeated phobic responses may result in a net progress in the more beneficial direction (‘phobotaxis’). phobotaxis See PHOBIC RESPONSE. phoE gene See PHO REGULON and PORIN. Pholiota See AGARICALES (Strophariaceae). Phoma A genus of fungi (order SPHAEROPSIDALES) which include many plant pathogens (see e.g. BLACKLEG sense 2, and GANGRENE sense 2). Colourless, ovoid conidia develop singly on conidiophores borne in brown, spherical or spheroidal, thin-walled, papillate, uniloculate, ostiolate pycnidia immersed in the substratum. Phomopsis See SPHAEROPSIDALES. phoR gene See PHO REGULON. phorbol ester 12-O-tetradecanoylphorbol-13-acetate. (See also ZEBRA.) -phore A suffix which signifies ‘carrier of’ or ‘bearer of’ – e.g. SPOROPHORE, IONOPHORE. Phormidium A genus of cyanobacteria of the LPP GROUP. Species occur e.g. with other filamentous cyanobacteria (e.g. Lyngbya, Oscillatoria) in mats on sediments in marine lagoons, saltmarshes etc. (See also STROMATOLITE and EMULCYAN.) phoront See TOMITE. phorophyte The host plant of an epiphyte. phoS gene See PHO REGULON. phosphatase (orthophosphoric monoester phosphohydrolase) Any enzyme which hydrolyses esters of phosphoric acid; phosphatases are classified (according to their pH optima) as acid phosphatases (EC 3.1.3.2) or alkaline phosphatases (EC 3.1.3.1). (See also ENZYMES.) They are widely distributed among living organisms, including many bacteria. Staphylococcal phosphatases. An acid phosphatase (pH optimum 5.2) is produced by most or all coagulase-positive staphylococci and (generally in smaller amounts) by some coagulase-negative strains. The enzyme may be secreted into the medium or may be loosely or tightly cell-bound – the proportions of each depending on strain and medium composition. An alkaline phosphatase (pH optimum 10.8) is apparently cell-bound. Phosphatase production may be demonstrated by growing the test organism on a solid medium containing the sodium salt of phenolphthalein diphosphate. After incubation, the plate is exposed to gaseous ammonia; colonies of phosphatase-producing strains become deep pink owing to the presence of free PHENOLPHTHALEIN. (Coagulase-negative strains which initially appear phosphatase-negative may produce phosphatase on prolonged incubation.) Phosphatase may be assayed e.g. using the artificial substrate p-nitrophenyl phosphate; pnitrophenol (yellow at alkaline pH) is released by acid or alkaline phosphatases and can be assayed spectrophotometrically (at 400 nm). (See also XP.) Staphylococcal phosphatase production appears to have little or no significance in pathogenicity. [Staphylococcal phosphatases: Book ref. 44, pp. 775–780.] In e.g. Escherichia coli a periplasmic alkaline phosphatase is produced in response to inorganic phosphate starvation: see PHO REGULON. phosphatase test (for milk) A test used to detect the presence of alkaline PHOSPHATASE in pasteurized MILK; the enzyme, which

is normally present in raw (i.e., untreated) milk, is inactivated by PASTEURIZATION – so that the test determines the efficiency of the pasteurization process. Milk containing alkaline-buffered disodium p-nitrophenyl phosphate is incubated at 37° C for 2 hours and then examined (e.g. by colorimetry) for the presence or intensity of yellow coloration due to p-nitrophenol. A falsepositive result can be obtained if, subsequent to pasteurization, the milk has been contaminated with phosphatase-producing organisms. Enzymic activity may reappear (‘reactivation’) in e.g. cream which has been treated by HTST pasteurization; reactivation can be promoted by the addition of MgCl2 . phosphate box See PHO REGULON. phosphate-controlled genes See PHO REGULON. phosphate potential See CHEMIOSMOSIS. phosphate regulon See PHO REGULON. phosphatidases Syn. PHOSPHOLIPASES. phosphatidic acid See LECITHIN. phosphatidylcholine See LECITHIN. phosphatidylethanolamine A product of esterification of ethanolamine (NH2 (CH2 )2 OH) with phosphatidic acid (see LECITHIN); it occurs e.g. in the CYTOPLASMIC MEMBRANE in many bacteria. phosphoadenosine phosphosulphate See PAPS. phosphoenolpyruvate carboxykinase See Appendix II(b). phosphoenolpyruvate carboxylase See Appendix II(b). phosphoenolpyruvate carboxytransphosphorylase See Appendix II(b). phosphoenolpyruvate-dependent phosphotransferase system See PTS. phosphoenolpyruvate synthase See Appendix II(b). phosphofructokinase See EMBDEN–MEYERHOF–PARNAS PATHWAY. 6-phosphogluconate pathway May refer to either HETEROLACTIC FERMENTATION or the HEXOSE MONOPHOSPHATE PATHWAY. phosphoketolase See HETEROLACTIC FERMENTATION. phospholipases (phosphatidases) Enzymes that hydrolyse phospholipids, releasing fatty acids or other groups (cf. LIPASES). Phospholipases A1 and A2 release fatty acids from, respectively, positions 1 and 2 of a phospholipid; phospholipases C and D release the base – in phosphorylated and unphosphorylated form, respectively – from e.g. phosphatidylcholines (lecithins), sphingomyelins etc. Phospholipases may act specifically (or preferentially) on particular phospholipids – see e.g. LECITHINASE and SPHINGOMYELINASE. phosphonoacetic acid (PAA) An ANTIVIRAL AGENT (used as disodium phosphonoacetate, D Fosfonet sodium) which is similar to, but more toxic than, PHOSPHONOFORMIC ACID. phosphonoformic acid (PFA) An ANTIVIRAL AGENT (used as trisodium phosphonoformate, NaO.CO.PO.(ONa)2 , D Foscarnet sodium) which acts by selectively inhibiting the DNA polymerases of a number of viruses (and the reverse transcriptase of retroviruses) – apparently by acting as an analogue of pyrophosphate. It is effective e.g. in the topical treatment of herpesvirus infections. phosphonomycin Syn. FOSFOMYCIN. phosphorelay See ENDOSPORE (sense 1). phosphorescence (1) The emission of light which occurs when certain substances absorb radiation; emission occurs as electrons excited to the triplet state (T1 ) are returning to the (unexcited) ground state (S0 ). The light emitted is of wavelength longer than that of the exciting radiation; emission typically lasts for 10
6 sec to 1 sec or longer. (cf. FLUORESCENCE.) (2) The term is sometimes applied, incorrectly, to BIOLUMINESCENCE. 579

phosphoribulokinase phosphoribulokinase See CALVIN CYCLE. phosphoroclastic split A reaction, analogous to hydrolysis, in which a molecule is cleaved with the addition of the components of phosphoric acid. The term is usually applied to the ‘pyruvic phosphoroclasm’ – the reaction pyruvate C H3 PO4 ! acetyl phosphate C formate (or CO2 and H2 ), a reaction which occurs e.g. in the MIXED ACID FERMENTATION and in the BUTYRIC ACID FERMENTATION, and which is also carried out by many SULPHATEREDUCING BACTERIA (including species of Desulfobacter, Desulfotomaculum and Desulfovibrio). However, the initial product of pyruvate cleavage is actually acetyl-CoA, acetyl phosphate being formed from acetyl-CoA by the action of phosphotransacetylase; acetyl phosphate is subsequently dephosphorylated in the presence of ADP to yield acetate and ATP (enzyme: acetokinase). phosphorylation potential See CHEMIOSMOSIS. phosphotransferase transport system See PTS. photic zone That zone of an aquatic habitat which is penetrable by sunlight and in which PHOTOSYNTHESIS can occur. In the upper part of the zone (euphotic zone) the amount of oxygen produced by photosynthesis exceeds that consumed by respiration (over a 24-hour period); the opposite situation occurs in the lower part of the zone (dysphotic zone), while between these zones (at the compensation level ) photosynthetic oxygen production and respiratory oxygen consumption are balanced. (cf. APHOTIC ZONE.) photoautotroph A phototrophic AUTOTROPH. Photobacterium A genus of Gram-negative bacteria of the family VIBRIONACEAE. Cells: straight rods, 0.8–1.3 ð 1.8–2.4 µm. Motile, with one to three unsheathed polar flagella. All species grow at 20° C but not at 40° C; P. phosphoreum and some strains of P. angustum can grow at 4° C. Growth requires NaC (opt. ca. 3% NaCl). Many strains are oxidase
ve. PHB accumulates in cells under certain conditions, but exogenous b-hydroxybutyrate is not utilized. Strains are sensitive to O/129. P. phosphoreum and P. leiognathi (formerly P. mandapamensis) exhibit bluegreen BIOLUMINESCENCE and occur in seawater, on and in marine animals (see also FISH SPOILAGE), and in specialized luminous organs in certain marine fish. (See also SUPEROXIDE DISMUTASE.) GC%: 40–44. Type species: P. phosphoreum. It has been suggested that the genus should include P. leiognathi and P. phosphoreum, and that Vibrio fischeri and V. logei should be transferred from the genus VIBRIO (q.v.) as P. fischeri and P. logei, respectively; it was also suggested that P. angustum is a biovar of P. leiognathi [SAAM (1985) 6 171–182]. photobiont A photosynthetic symbiont. (See also PHYCOBIONT.) photochromogen Any strain of MYCOBACTERIUM in which a period of exposure to light is necessary for the development of pigmentation. (cf. SCOTOCHROMOGEN; NON-PHOTOCHROMOGEN.) Photocyta (photocytes) A (suggested) URKINGDOM (sense 2) comprising the halobacteria (e.g. Halobacterium spp) and the EUBACTERIA, the proposed relatedness of these organisms being based on three-dimensional RIBOSOME structure [PNAS (1985) 82 3716–3720]; it has been proposed that the photocytes, together with the methanogens, gave rise to the Eocyta (see ARCHAEBACTERIA) and the eukaryotes [Nature (1986) 319 626]. photocytes See PHOTOCYTA. photodissociation Light-induced chemical dissociation (see e.g. CARBON MONOXIDE (b)). photodynamic effect Light-induced damage or death which occurs when some microorganisms (particularly bacteria) are stained with certain fluorescent dyes (e.g. ACRIDINE ORANGE, EOSIN, ROSE BENGAL) and subsequently exposed to strong light

under aerobic conditions; this effect appears to be due largely to the formation of SINGLET OXYGEN [JAB (1985) 58 391–400]. ETHIDIUM BROMIDE can cause a light-induced nicking of DNA. photoheterotroph A phototrophic HETEROTROPH. photoinduction and photoinhibition (in fungi) In many fungi, light is needed for, or encourages, the development of fruiting bodies or spores, or the formation of particular compounds (photoinduction); in other fungi light inhibits growth and/or sporulation (photoinhibition). Commonly, light in the blue-violet region of the spectrum is effective in photoinduction/photoinhibition. In some cases light may be needed only for the completion of a particular phase of development, e.g., the initiation of fruiting in Pyronema omphalodes, or the development of the pileus in Lentinus lepideus (cf. STAG’S HORN FUNGUS). Conidium formation is photoinducible in e.g. Trichoderma viride, and in Choanephora cucurbitarum it is stimulated by darkness preceded by a period of exposure to light. In some species of Coprinus fruiting bodies develop more rapidly in the light, i.e., light encourages fruiting but is not essential for it. In Phycomyces blakesleeanus carotenoid synthesis is stimulated by light, while some species of Fusarium and Verticillium which normally form negligible amounts of carotenoids form significant amounts of these compounds in the presence of light. Photoinhibition of growth and/or sporulation occurs e.g. in at least some species of Alternaria and Penicillium. In e.g. Alternaria cichorii, A. tomato and Botrytis cinerea, conidium formation is controlled by a photoreceptor system referred to as mycochrome. On exposure to blue light mycochrome adopts the MNUV form, in the presence of which conidia are not formed and conidiophores may revert to vegetative hyphae; on exposure to near-ultraviolet mycochrome adopts the MB form, in the presence of which conidia can be formed. In A. cichorii the blue-light inhibition of conidium formation can be reversed by a period of darkness [CJB (1986) 64 1016–1017]. photoinhibition See PHOTOINDUCTION AND PHOTOINHIBITION. photokinesis A KINESIS (sense 1 or 2) in which the stimulus is light intensity. photolithotroph See LITHOTROPH. photolyase In some bacteria (including Escherichia coli ): an enzyme which can repair thymine dimers in DNA damaged by ULTRAVIOLET RADIATION; the energy needed for repair is derived from (visible) light. In vitro studies on the repair of thymine dimers may be facilitated by using the reagent potassium permanganate (KMnO4 ) [NAR (1998) 26 3940–3943]. photomicrograph A photograph obtained by PHOTOMICROGRAPHY. photomicrography Photography of microscopic objects through a microscope; it may involve the attachment of a camera to a microscope, or the use of a photomicroscope: a microscope which incorporates a camera. (cf. MICROPHOTOGRAPHY.) photomicroscope See PHOTOMICROGRAPHY. photomorphogenesis The formation of new cells or tissues under the stimulus of light. photoorganotroph See ORGANOTROPH. photophobic response A light-induced PHOBIC RESPONSE. photophosphorylation See PHOTOSYNTHESIS and PURPLE MEMBRANE. photoreactivation (photorestoration) A mechanism of DNA REPAIR in which pyrimidine dimers (formed as a result of exposure to ULTRAVIOLET RADIATION) are cleaved by exposure of the cells to light of wavelength ca. 300–600 nm; in Escherichia coli the reaction is mediated by the product of the phr gene (DNA photolyase) which, when bound to a pyrimidine dimer, 580

photosynthesis photorestoration Syn. PHOTOREACTIVATION. photosynthate Any carbohydrate product of photosynthesis. photosynthesis In certain (photosynthetic) organisms: the process in which radiant energy is absorbed by specialized CHLOROPHYLL-containing pigment system(s) and is converted to forms of energy (including chemical energy) which can be used for metabolic and other purposes (cf. PURPLE MEMBRANE); radiation of wavelengths in the visible spectrum is used by plants, ALGAE and photosynthetic bacteria (including CYANOBACTERIA and members of the RHODOSPIRILLALES), while some photosynthetic bacteria can also use infrared radiation. Light reaction refers, collectively, to those photochemical events involved in the conversion of radiant energy; dark reaction (D light-independent reaction) generally refers, collectively, to those reactions in which photosynthetically derived chemical energy is used for the synthesis of carbohydrate(s). In all cases, the conversion of radiant energy occurs in a specialized ENERGY-TRANSDUCING MEMBRANE containing CHLOROPHYLLS or bacteriochlorophylls, accessory pigments, and components of ELECTRON TRANSPORT CHAIN(S). Within such a photosynthetic membrane there are well defined chlorophyllcontaining REACTION CENTRES towards which radiant energy is channelled via LIGHT-HARVESTING COMPLEXES. On excitation of a reaction centre with radiant energy, the mid-point REDOX POTENTIAL of the reaction centre chlorophyll changes from a high positive value to a high negative value, and electrons are consequently ejected (‘charge separation’) from the chlorophyll (the ‘primary electron donor’). The ejected electrons, by virtue of the high negative redox potential of their source, are associated with a certain amount of energy; these electrons can therefore pass down an electron transport chain in the direction of less negative (or more positive) potentials and, in doing so, can provide the energy for (a) the transmembrane pumping of protons (thereby contributing to a proton motive force – see CHEMIOSMOSIS) or (b) the reduction of pyridine nucleotides. The precise nature of photosynthetic energy conversion differs among the different groups of photosynthetic organisms. (a) Photosynthesis in bacteria of the Rhodospirillales (anoxygenic photosynthesis) occurs only under anaerobic conditions, and only one type of reaction centre appears to occur in a given species. In the ‘purple’ photosynthetic bacteria (RHODOSPIRILLINEAE), electrons which have been ejected from the bacteriochlorophyll follow a cyclic path: e.g. from the bacteriochlorophyll to BACTERIOPHAEOPHYTIN and thence – probably via QUINONES, b-and c-type cytochrome(s) – back to the reaction centre; this cyclic electron flow causes the transmembrane pumping of protons, i.e., it generates pmf. The pmf can be used, by means of membrane-bound PROTON ATPASES, for the synthesis of ATP (photophosphorylation). At least some of these organisms can obtain reducing power by REVERSE ELECTRON TRANSPORT; in this process, photosynthetically generated pmf is used to reduce NADC at a membrane-bound NADH dehydrogenase – electrons being obtained from an external electron donor (such as hydrogen or sulphide). NADPH is obtained via a TRANSHYDROGENASE. In the ‘green’ photosynthetic bacteria (CHLOROBIINEAE), the light-energized reaction centre reaches a much lower (more negative) potential (ca.
550 mV) than is the case in the purple bacteria, and – consequently – the ejected electrons are able to effect the reduction of NADC (the Em,7 of the NADC /NADH redox couple being
320 mV); the reduction of NADC involves a non-cyclic electron transport path which is believed to include iron–sulphur proteins. Electrons which are removed from the

absorbs light energy and cleaves the bonds between the bases (‘monomerization’). [Action mechanism of E. coli DNA photolyase: JBC (1987) 262 478–485, 486–491, 492–498.] The phr gene product may also play a role in UvrABC-dependent repair of UV damage in the dark [JB (1985) 161 602–608]. Photoreactivation does not occur e.g. in Bacillus subtilis. photoreceptor An organelle or region specialized for receiving light stimuli: see e.g. EYESPOT (sense 1), STENTORIN and STENTOR. photoreduction In photosynthetic organisms (see PHOTOSYNTHESIS): any light-dependent reduction – e.g., the reduction of NADC , or of CO2 via the Calvin cycle; electron donors used in photoreductions include e.g. water and H2 S. In certain algae (e.g. Chlorella, Chlamydomonas, Scenedesmus) hydrogen can act as electron donor for the reduction of CO2 ; HYDROGENASE is involved, and the process can occur only after the algae have been incubated anaerobically with hydrogen, followed by illumination with low levels of light. photorespiration (C2 carbon oxidation cycle) In photosynthetic organisms which fix CO2 via the CALVIN CYCLE: a lightdependent process in which oxygen is consumed and CO2 is evolved, but which is distinct from true (energy-yielding) RESPIRATION; photorespiration occurs under conditions of relatively high O2 and low CO2 concentrations and high light intensities, and results from the ability of RIBULOSE 1,5BISPHOSPHATE CARBOXYLASE–OXYGENASE (RuBisCO) to act as an oxygenase under these conditions. RuBisCO catalyses the oxygenation and cleavage of ribulose 1,5-bisphosphate (RuBP) to 3-phosphoglycerate and 2-phosphoglycolate. (The dependence of photorespiration on light is thus explained by the need for photosynthesis to drive the CALVIN CYCLE and hence supply RuBP.) The 2-phosphoglycolate is dephosphorylated to glycolate which may be excreted – e.g. by certain microalgae and cyanobacteria (often resulting in relatively high levels of glycolate in aquatic environments) – and/or may be metabolized further: e.g. glycolate ! glyoxylate ! glycine ! serine ! hydroxypyruvate ! glycerate ! 3-phosphoglycerate (the ‘glycolate pathway’). The step glycolate ! glyoxylate is also an O2 -consuming step (catalysed by glycolate oxidase); H2 O2 generated during the reaction is rapidly degraded by catalase. (The glycolate ! glyoxylate conversion occurs in PEROXISOMES in photosynthetic eukaryotes.) The 3-phosphoglycerate generated by the glycolate pathway and by the original cleavage of RuBP by RuBisCO may then enter the Calvin cycle. An alternative pathway for glycolate metabolism in some organisms involves the oxidation of glycolate to glyoxylate which is then converted to glycerate via tartronic semialdehyde (TSA). In either pathway, CO2 is lost: in the glycolate pathway during the glycine ! serine reaction (during which two glycine molecules are converted to one of serine with loss of both CO2 and NH3 ), and in the TSA pathway during the formation of TSA from glyoxylate (2CHO.COOH ! CHO.CHOH.COOH C CO2 ). Photorespiration thus results in a net loss of photosynthetic productivity. Its physiological significance is still not understood. In green algae, photorespiration is suppressed by CO2 -concentrating mechanisms which become operative at low CO2 levels. [Review of photorespiration: ARPphys (1984) 35 415–442.] (cf. WARBURG EFFECT.) A process very similar to photorespiration (although independent of light) occurs in some chemolithoautotrophic bacteria (e.g. ‘Alcaligenes eutrophus’, Thiobacillus neapolitanus) which fix CO2 via the Calvin cycle; by analogy with photorespiration, this process has been called ‘chemorespiration’. [Book ref. 115, pp. 129–173.] 581

photosynthesis photosystem II

photosystem I

(PS-II)

(PS-I) P*700

−1.0

iron-sulphur proteins

P*680

E m(volts)

−0.5

ferredoxin phaeophytin quinones

0

NADP

cytochrome b6 / f complex

+

light

plastocyanin P700

0.5 H2O 2e−

1.0

1 2

light P680

O2 + 2H+

PHOTOSYNTHESIS. Simplified ‘Z scheme’ for non-cyclic, oxygenic photosynthetic electron transport (scale approximate). Each photosystem (PS-I and PS-II) consists of a reaction centre together with its associated accessory pigments. P680 and P700 represent the chlorophylls in the reaction centres of PS-II and PS-I, respectively; PŁ680 and PŁ700 represent the excited state in P680 and P700 , respectively. The cytochrome b6 /f complex includes cyts b6 and f, quinone, and a Rieske iron–sulphur protein.

reaction centre during non-cyclic electron flow must be replaced if photosynthesis is to continue; these electrons are obtained (via a pathway containing cytochrome c555 ) from certain substrates (e.g. sulphide). Water is never used as an electron donor, so that this type of photosynthesis is always anoxygenic. The green photosynthetic bacteria appear to be also capable of cyclic elctron flow – electrons returning to the reaction centre via a menaquinone and cytochrome c555 . In many photosynthetic bacteria the dark reaction involves the fixation of carbon dioxide via the CALVIN CYCLE; however, at least some of the green photosynthetic bacteria use the REDUCTIVE TRICARBOXYLIC ACID CYCLE for this purpose. Apart from photochemical reactions, most of the reactions which occur in photosynthetic bacteria are known to occur in nonphotosynthetic species; thus, e.g. the Calvin cycle occurs in chemolithotrophic bacteria. (b) Photosynthesis in algae and cyanobacteria. Photosynthesis in these organisms differs from that described in (a) in that: (i) it occurs aerobically; (ii) it involves a composite photosynthetic system (as shown in the figure); (iii) it involves non-cyclic electron flow in which the terminal electron donor, water, is oxidized to oxygen – such photosynthesis thus being oxygenic. [How does PSII split water? (review) TIBS (1996) 21 44–49.] (Some species of cyanobacteria, e.g. Oscillatoria limnetica, can also carry out DCMU-insensitive, anaerobic, anoxygenic photosynthesis in which H2 S is used as external electron donor.) (See also PHOTOREDUCTION.) Oxygenic photosynthesis in algae

and cyanobacteria (and Prochloron) closely resembles that in higher green plants. The characteristic (oxygenic, non-cyclic) mode of photosynthesis in algae and cyanobacteria is generally depicted by the socalled Z scheme (see figure). In this scheme, the midpoint redox potential of chlorophyll in the reaction centre of photosystem II (PS-II) changes from ca. C1.0 volt to between ca.
550 and
600 mV when the reaction centre receives a photon of light; electrons which are ejected from PS-II (and which are replaced by the oxidation of water) flow ‘downhill’ (i.e., towards less negative or more positive potentials) via QUINONES (generally believed to include plastoquinones), the CYTOCHROME b6 /f complex, and PLASTOCYANIN, to the reaction centre of photosystem I (PS-I). This electron flow is associated with the development of a proton gradient across the thylakoid membrane. In chloroplasts the inner surface of the thylakoid membrane becomes positive with respect to the outer (stromal) surface; the associated pmf can be utilized by membrane-bound PROTON ATPASES for ATP synthesis (photophosphorylation) – the CF1 part of the ATPase, and (hence) ATP synthesis, occurring at the outer surface of the thyalkoid membrane. On excitation of PS-I by light, the midpoint redox potential of the reaction centre chlorophyll changes to a value which exceeds ca.
1.0 volt; electrons ejected from the reaction centre of PS-I can therefore flow downhill to the ferredoxin-NADPC reductase complex and can be used for the reduction of NADPC to NADPH. A revised eukaryotic Z scheme includes the reduction of NADP by PSII [TIBS (1996) 21 121–122]. 582

phycobilisomes Phragmobasidiomycetidae A subclass of fungi (class HYMENOMYCETES) characterized by the formation of phragmobasidia (see BASIDIUM). Orders [Book ref. 64, p. 189]: AURICULARIALES, SEPTOBASIDIALES, TREMELLALES. phragmobasidium See BASIDIUM. phragmoplast In e.g. some green algae (e.g. Chara): a plate which develops in the cleavage plane between two newly forming cells during the telophase stage of MITOSIS; it consists of microtubules of the persistent mid-region of the mitotic spindle together with vesicles (derived from dictyosomes) which collect between the microtubules. (cf. PHYCOPLAST.) phragmosporae See SACCARDOAN SYSTEM. phthalimide antifungal agents A group of agricultural nonsystemic ANTIFUNGAL AGENTS which includes CAPTAFOL, CAPTAN, FOLPET etc. phthalylsulphathiazole See SULPHONAMIDES. phthiocerols Complex waxes found in mycobacteria [JGM (1983) 129 859–863]. phthisis Syn. TUBERCULOSIS. phycobilin See PHYCOBILIPROTEINS. phycobiliproteins (biliproteins) Water-soluble pigments which occur in CYANOBACTERIA, in algae of the RHODOPHYTA, and in CRYPTOPHYTES. In cryptophytes the pigments occur between the thylakoids and are antigenically unrelated to the cyanobacterial and rhodophytan pigments (which occur bound to thylakoids – see PHYCOBILISOMES). A phycobiliprotein consists of a protein ‘monomer’ comprising two distinct polypeptide chains (a and b), each of which is linked covalently (via a thioether bond) to an open-chain tetrapyrrole chromophore (phycobilin or bilin). The monomers tend to form trimers or hexamers which are the structural units of phycobilisomes. Phycobiliproteins function as light-harvesting pigments for photosystem II (see PHOTOSYNTHESIS); there are three main classes: allophycocyanins (lmax 650–671 nm), phycocyanins (lmax 617–620 nm), and phycoerythrins (including phycoerythrocyanin: lmax 545–568 nm). Allophycocyanins and phycocyanins apparently occur in all cyanobacteria and red algae; phycoerythrins occur in most red algae and in many cyanobacteria, phycoerythrocyanin occurs in some cyanobacteria (e.g. Anabaena variabilis, ‘Mastigocladus laminosus’ ). Cryptophytes contain either phycocyanin or phycoerythrin, according to species. In cyanobacteria, the content of phycobiliproteins can be affected by many environmental factors, including temperature, CO2 concentration, nitrogen starvation, wavelength and intensity of light [Book ref. 76, pp. 182–188]; in addition to its function as a photopigment, phycocyanin serves as a nitrogen reserve in cyanobacteria, being degraded by a specific protease induced during nitrogen starvation both in vegetative cells and in differentiating HETEROCYSTS. [Structure and function of cyanobacterial phycobiliproteins: Book ref. 75, pp. 23–42; the phycocyanin operon and light regulation of its expression in Anabaena: EMBO (1987) 6 871–884.] phycobilisomes Structures, each ca. 20–70 nm across, which are attached in regular arrays to the surface of thylakoid membranes in CYANOBACTERIA (cf. GLOEOBACTER) and red algae (RHODOPHYTA). Phycobilisomes are composed mainly of PHYCOBILIPROTEINS together with ‘linker’ polypeptides; they vary in composition and morphology (being typically hemidiscoid or hemispherical) according e.g. to species. The (mainly nonpigmented) linker polypeptides seem to have many functions – e.g. to stabilize the specific structure of phycobilisomes, to modify the phycobiliproteins so as to promote unidirectional

[Excited-state redox potentials in the Z scheme: TIBS (1985) 10 382–383.] In addition to non-cyclic electron flow, a pmf-generating cyclic flow of electrons can occur via PS-I and cytochromes b6 and f. There is also evidence for a cyclic flow of electrons around PS-II, possibly via cyt b559 . [Photosynthetic electron transfer: Book ref. 85, pp. 95–148.] In algae and cyanobacteria the dark reaction characteristically involves the CALVIN CYCLE. Inhibitors of the photosynthetic electron transport chain include e.g. dibromomethyl-isopropyl p-benzoquinone (DBMIB) and DCMU, both of which inhibit electron flow between PS-II and PS-I, and hydroxylamine, which blocks electron flow from water to the reaction centre of PS-II. Experimental electron donors to PS-II include e.g. benzidine and catechol, while electron acceptors for PS-II include e.g. ferricyanide; electron donors for PS-I include e.g. reduced phenylenediamines, while electron acceptors for PS-I include e.g. ferricyanide and METHYL VIOLOGEN. [Molecular biology of the photosynthetic apparatus: Book ref. 163.] See also CAROTENOID BAND SHIFT; ENHANCEMENT EFFECT; HILL REACTION; PHOTORESPIRATION; RED DROP; WARBURG EFFECT.) photosynthetic bacteria A term which usually refers to bacteria of the RHODOSPIRILLALES (cf. CYANOBACTERIA). photosystems I and II See PHOTOSYNTHESIS. phototaxis A TAXIS in which an organism moves, directly or indirectly, from a region of low light intensity to one of higher light intensity (positive phototaxis) or vice versa (negative phototaxis). (A phototactic organism may be positively phototactic at low light intensities but negatively phototactic at high light intensities.) In phototactic bacteria, changes in light intensity may affect the frequency of tumbling (in peritrichously flagellated organisms) and/or speed of swimming (cf. KINESIS sense 1). In purple photosynthetic bacteria, at least, phototaxis appears to be mediated by changes in proton motive force (cf. AEROTAXIS and CHEMOTAXIS) resulting from changes in the rate of energy conversion in the photosynthetic reaction centre. [Role of pmf in sensory transduction: ARM (1983) 37 551–573.] Halobacterium salinarium responds differently to light of different wavelengths. The cells of this species are bipolarly flagellated; they swim in the direction of the long axis of the cell, with spontaneous reversals in direction at intervals of ca. 10–50 sec. A sudden decrease in yellow-green light or a sudden increase in blue/UV light elicits an extra reversal in direction, while an increase in yellow-green light or a decrease in blue/UV light leads to a suppression of the spontaneous reversals. (See also SLOW-CYCLING RHODOPSIN.) Thus cells tend to acumulate in regions illuminated by yellowgreen or white light (areas optimum for photophosphorylation by the purple membrane) but avoid areas exposed to (possibly damaging) UV radiation [SEBS (1983) 36 207–222]. See also STENTOR. phototopotaxis A light-induced TOPOTAXIS. phototroph An organism which can use light (and, in some species, infrared radiation) as a primary source of energy for metabolism and growth. (See also PHOTOSYNTHESIS and PURPLE MEMBRANE.) Some phototrophs are facultative CHEMOTROPHS.) (See also LITHOTROPH and ORGANOTROPH.) phototropism See TROPISM (sense 1). phoU gene See PHO REGULON. phr gene See PHOTOREACTIVATION. Phragmidium See UREDINIOMYCETES. 583

phycobiont energy flow within the phycobilisomes and to the reaction centres, and to link phycobilisomes to the photosynthetic membranes. In general, each phycobilisome comprises two major structural domains: (i) a ‘core’ (consisting of two or three cylindrical elements), and (ii) five or six ‘rods’ (composed of stacked discs) that radiate from the core to form the hemidiscoid or hemispherical structure. The core is composed of allophycocyanin (APC) and is anchored to the thylakoid membrane by a linker polypeptide. Where the rods are adjacent to the core, they consists of discs of phycocyanin (PC), but discs of phycoerythrin (PE) and/or phycoerythrocyanin (PEC), when present, occur at the periphery. Absorbed light energy is transferred from the periphery to the core, and thence to chlorophyll a – thus: PE/PEC ! PC ! APC ! Chl a; this transfer is almost 100% efficient. [Structure of a ‘simple’ phycobilisome (in Synechococcus): Ann. Mic. (1983) 134 B 159–180. Phycobilisome structure: JB (1993) 175 575–576.] phycobiont An algal symbiont. In lichenology, ‘phycobiont’ commonly refers to the main algal or cyanobacterial partner in a lichen, although in the latter case the term ‘cyanobiont’ is more appropriate. The term photobiont is a useful non-specific term for the principal photosynthetic partner in a LICHEN. (See also PHYCOZOAN.) phycocyanins See PHYCOBILIPROTEINS. phycoerythrins See PHYCOBILIPROTEINS. phycoerythrocyanin See PHYCOBILIPROTEINS. phycology The study of ALGAE. Phycomyces See MUCORALES. phycomycetes See LOWER FUNGI. phycomycosis See ZYGOMYCOSIS and EQUINE PHYCOMYCOSIS. Phycopeltis A genus of algae closely related to TRENTEPOHLIA. The thallus is typically a circular monostromatic disc (ca. 1–3 mm diam.) of compacted, branched filaments. Species occur mainly as epiphytes, growing on – not beneath – the leaf cuticle (cf. CEPHALEUROS), and also as photobionts in certain (mainly tropical) lichens. phycoplast In many green algae: a plate which develops in the cleavage plane between two newly forming cells in species in which the mitotic spindle is non-persistent; it contains microtubules orientated perpendicular to the axis of the former spindle. (cf. PHRAGMOPLAST.) phycosymbiodeme See CEPHALODIUM. phycotoxin Any TOXIN produced by an alga (see e.g. BREVETOXINS, CIGUATERA, GONYAUTOXINS, PRYMNESIUM, SAXITOXIN, ULVA) or – traditionally – by a cyanobacterium (‘blue-green alga’: see e.g. ANABAENA, APHANIZOMENON, LYNGBYA, MICROCYSTIS, NODULARIA). phycovirus A VIRUS which infects one or more ALGAE. (cf. CYANOPHAGE.) Several polyhedral dsDNA viruses have been observed in green algae: e.g. a tailed polyhedral virus, resembling (at least superficially) a tailed bacteriophage, has been found in Uronema gigas [Virol. (1980) 100 156–165, 166–174], and various polyhedral dsDNA viruses have been observed in Chlorella-like algae, including the zoochlorellae of Paramecium bursaria and Hydra viridis [PNAS (1982) 79 3867–3871]. phycozoan A term proposed to refer to a ‘compound organism’ in which cells (or chloroplasts) of an alga (the phycobiont) live within the tissues or cells of an animal (the zoobiont: an invertebrate) [Book ref. 129, pp. 5–17]. (See e.g. ZOOCHLORELLAE and ZOOXANTHELLAE; cf. LICHEN.) phyletic classification Syn. PHYLOGENETIC CLASSIFICATION.

Phyllactinia See ERYSIPHALES. Phyllobacterium A genus of Gram-negative bacteria of the RHIZOBIACEAE. Cells (in vitro) are straight rods which, in liquid media, form characteristic star-shaped clusters. Acid is formed from a wide range of carbohydrates. GC%: 59.6–61.3. Type species: P. myrsinacearum. P. myrsinacearum and P. rubiacearum occur as pleomorphic cells (rod-shaped, ellipsoidal or branched) within leaf nodules which they induce in certain tropical plants of the Rubiaceae (e.g. madder), Myrsinaceae, Myrtaceae and Dioscoreaceae (e.g. yam). They have not been shown to be capable of nitrogen fixation. [Book ref. 22, pp. 254–256.] phyllocladia See STEREOCAULON. phyllody (plant pathol.) A malformation in which normal floral components are replaced by leaf-like structures; it is a symptom of certain plant diseases: e.g. green ear disease of millet (Pennisetum typhoides) and other grasses caused by Sclerospora graminicola. Phyllopertha horticola EPV See ENTOMOPOXVIRINAE. phylloplane The surface(s) of a leaf. (cf. PHYLLOSPHERE.) [Book ref. 158.] Phylloporus See BOLETALES. phylloquinone See QUINONES. phyllosphere (1) Syn. PHYLLOPLANE. (2) The region immediately surrounding, and influenced by, a leaf. [Quantification of bacterial sugar consumption in the phyllosphere: PNAS (2001) 98 3446–3453.] (See also RHIZOSPHERE.) Phyllosticta See SPHAEROPSIDALES. phylogenetic classification (phyletic classification) Any form of classification in which the aim is to group organisms according to their ancestral lineage (i.e. evolutionary relationships). (cf. PHENETIC CLASSIFICATION.) phylogeny The range of developmental stages in the evolution of an organism. (cf. ONTOGENY.) phylotype A taxon which is defined solely by nucleic acid sequence data (no representative species of the taxon having been cultured). [Example of use: JCM (1999) 37 1469–1473.] phylum A taxonomic rank (see TAXONOMY and NOMENCLATURE). Physarales See MYXOMYCETES. Physarum A large genus of slime moulds (class MYXOMYCETES) which usually form sporangia (some species form plasmodiocarps). P. polycephalum is widely used in laboratory studies. It generally forms a robust, conspicuous yellow phaneroplasmodium in which a network of major and subsidiary ‘veins’ leads to the advancing front edge. The sporangia are stalked, greyish, and typically multilobed. Physcia A genus of small foliose LICHENS (order LECANORALES); photobiont: a green alga. The thallus generally consists of grey or greyish-brown, often pruinose, narrow branching lobes which are often radially orientated to form a rosette. Several species have cilia; some have soredia. Apothecia: lecanorine, with grey or blue-black, often pruinose discs. Ascospores: brown, oneseptate. Species are generally nitrophilous, occurring e.g. on bark and/or on rocks. physiological heterothallism See HETEROTHALLISM. physiological race (mycol.) Organisms which are morphologically similar to, but which differ in physiological (and/or other) characteristics from, other members of the same FORMA SPECIALIS. A given race may be designated by a number, letter etc (see e.g. NOMENCLATURE). physode See PHAEOPHYTA. phytoalexins Low-MWt antimicrobial compounds which are synthesized by, and accumulate in, higher plants exposed to 584

Phytophthora Phytomastigophorea (the phytoflagellates) A class of flagellated protozoa (subphylum MASTIGOPHORA) which either have chloroplasts or bear an obvious relationship to other members which have chloroplasts. Most phytoflagellates can also be regarded as algae and are alternatively classified in algal taxonomic schemes. Orders: Chloromonadida (the CHLOROMONADS); Chrysomonadida (the CHRYSOPHYTES); Cryptomonadida (the CRYPTOPHYTES); Dinoflagellida (the DINOFLAGELLATES); Euglenida (the EUGLENOID FLAGELLATES); Heterochlorida (unicellular, flagellate and/or amoeboid members of the XANTHOPHYCEAE); Prasinomonadida (cf. PRASINOPHYCEAE); Prymnesiida (D PRYMNESIOPHYCEAE); Silicoflagellida (the SILICOFLAGELLATES); Volvocida (including genera such as CHLAMYDOMONAS and VOLVOX). Phytomonas (1) A genus of protozoa (family TRYPANOSOMATIDAE) parasitic in certain plants – particularly lactiferous plants (e.g. Euphorbiaceae) but also e.g. coffee plants (see e.g. PHLOEM NECROSIS) and palms; they are transmitted by sap-sucking bugs. The organisms occur in the promastigote form and are usually ca. 20 µm in length; some species have been grown in vitro. [Plant diseases caused by Phytomonas: ARPpath. (1984) 22 115–132; cultivation of P. fran¸cai, a species associated with a root rot disease of cassava (Manihot esculenta): JP (1986) 33 511–513.] (2) Obsolete name for Xanthomonas. phytoncide (plant pathol.) A broad term for any substance which is produced (constitutively or inducibly) by a plant and which confers on that plant resistance to disease or infestation by killing or inhibiting the growth of a potential pathogen or parasite. phytone A proteolytic digest (by PAPAIN) of plant material (e.g. soybean meal), used in certain media (see e.g. TRYPTICASE–SOY AGAR). phytopathology Plant pathology. Phytophthora A genus of fungi (order PERONOSPORALES) which include some important phytopathogenic species. In many geographical regions, P. infestans (causal agent of LATE BLIGHT of potato) appears to overwinter as mycelium in infected tubers. In the spring, when the tubers produce shoots, the fungus grows into the developing shoots and subsequently gives rise to distinctive sporangiophores – bearing lemon-shaped sporangia – which emerge from the stomata of the leaves; the sporangia are dispersed e.g. by wind. A sporangium germinates to form either zoospores or a germ tube, depending on conditions. A zoospore subsequently encysts and later germinates, forming a germ tube; a germ tube may enter a host plant by means of an APPRESSORIUM or, directly, via a stoma. Within the new host a branching mycelium develops intercellularly, and elongated haustoria are formed; later, sporangiophores emerge from the stomata. Sexual reproduction occurs between strains of appropriate MATING TYPE. During gametangial development the oogonial initial penetrates and grows through the antheridium such that, when fully developed, the expanded, globose oogonium carries the antheridium as an encircling collar around its base; a fertilization tube develops between the two gametangia. The sexually-derived thick-walled oospore typically germinates to form a germ tube that terminates in a zoosporangium. Oospore formation is very rare in most geographical regions – though not in Mexico. Other pathogenic species include e.g. P. cactorum (see CROWN ROT); P. cinnamomi, a worldwide pathogen of various trees and other plants (see e.g. JARRAH DIEBACK); P. citricola (see BLEEDING CANKER); P. fragariae (see RED CORE); P. megasperma var. sojae (causal agent of root and stem rot of soybean) [review: Book ref. 58, pp. 19–30]; P. palmivora (see BLACK POD DISEASE); and P. parasitica (see GUMMOSIS). P. syringae causes e.g. storage rot of apples and pears.

certain (pathogenic and non-pathogenic) microorganisms – or to heavy metals (e.g. copper, mercury), detergents or certain other chemicals, ultraviolet radiation or physical (e.g. freeze–thaw) damage. Phytoalexins are formed by many angiosperms (particularly by members of the Leguminosae and Solanaceae) and by some gymnosperms; they have not been detected in lower plants. Under pre-stimulus conditions, phytoalexins may be either absent from plant tissues or present in extremely low concentrations. The production of phytoalexins appears to be a local effect in the plant – their translocation has yet to be conclusively demonstrated; if phytoalexins are involved in a plant’s natural resistance to disease, their localized accumulation may be an important factor in such resistance. In some cases the ability to produce phytoalexin(s) appears to enable a plant to resist the development of disease following infection by a pathogen; thus, e.g. resistance of the French bean to Colletotrichum lindemuthianum seems to correlate with the accumulation of a phytoalexin, phaseollin. In other cases the accumulation of phytoalexins appears not to be the sole factor which determines the plant’s resistance to disease. Pathogens which are able successfully to invade a plant may (i) fail to induce the production of phytoalexins; (ii) be relatively insensitive to the phytoalexin(s) produced; or (iii) be able to convert a phytoalexin to an inactive form (see e.g. KIEVITONE and PISATIN). (See also HYPERSENSITIVITY sense 2.) Elicitors of phytoalexins, i.e. specific chemical entities which promote the synthesis of phytoalexins, include the polypeptide monilicolin A (which elicits PHASEOLLIN) and various polysaccharides (such as b-1,3- and b-1,6-glucans and CHITOSAN) present e.g. in fungal cell walls or culture filtrates. Physical damage to plant tissues may cause release of the plant’s own elicitors (constitutive or endogenous elicitors). [Phytoalexins and their elicitors: ARPphys. (1984) 35 243–275.] Phytoalexins are structurally/chemically diverse compounds; they include e.g. CAMALEXIN; CAPSIDIOL; DEOXYHEMIGOSSYPOL; FALCARINDIOL; GLYCEOLLIN; HIRCINOL; IPOMEAMARONE; KIEVITONE; LUBIMIN; MOMILACTONES (see also WL 28325); ORCHINOL; PHASEOLLIN; PISATIN; PTEROSTILBENE; RISHITIN; VIGNAFURAN; VINIFERINS; and WYERONE. (cf. AVENACIN; CAFFEIC ACID; CHLOROGENIC ACID; PATHOGENESISRELATED PROTEINS.) [Phytoalexins (structure, role etc.): ARPpath. (1999) 37 285–306.] phytobiont A plant symbiont – e.g. the plant partner in a MYCORRHIZA. phytoflagellates See PHYTOMASTIGOPHOREA. phytoflavin See FLAVODOXINS. phytoglycogen A type of GLYCOGEN-like polysaccharide found e.g. in certain algae. (cf. CYANOPHYCEAN STARCH.) phytohaemagglutinin (PHA) (1) A mitogenic LECTIN from the red kidney bean, Phaseolus vulgaris; it can agglutinate erythrocytes, and it binds to both B and T cells but is mitogenic mainly in T cells. PHA activity requires Ca2C and Mg2C and is inhibited e.g. by N-acetyl-D-galactosamine. (2) Any plant lectin which can agglutinate erythrocytes. phytohormones (plant hormones) Compounds which are produced by plants and which regulate the plants’ own metabolism, cell division, seed germination etc; they include ABSCISIC ACID, AUXINS, CYTOKININS, ETHYLENE and GIBBERELLINS. phytokinins See CYTOKININS. 585

phytoplankton phytoplankton See PLANKTON. phytoplasma See MLOS. Phytoreovirus (plant reovirus subgroup 1) A genus of PLANT VIRUSES of the REOVIRIDAE. Genome: 12 linear dsRNA molecules. Replication occurs in cytoplasmic viroplasms; mRNA transcripts are capped. Transmission occurs propagatively via cicadellid leafhoppers; transovarial transmission occurs in the insect vector. The genus includes WOUND TUMOUR VIRUS (type species), RICE DWARF VIRUS, and RICE GALL DWARF VIRUS. [Review: Book ref. 83, pp. 505–563.] phytotoxin (1) A TOXIN produced by a microorganism and active against a plant or against plant cells/tissues. (2) A toxin produced by a plant. phytotron An apparatus consisting of a chamber within which plants etc can be grown under a variety of accurately controlled conditions of temperature, light intensity, humidity, etc. pI See ISOELECTRIC POINT. Pi Inorganic orthophosphate (PO4 3
) pi particle See PSEUDOCAEDIBACTER. p protein (Pi protein) See R6K PLASMID. pian Syn. YAWS. pian bois (forest yaws) A form of LEISHMANIASIS in which the pathogen spreads, typically via the lymphatic route, producing a chain of ulcers in the peripheral lymphatic system; pian bois occurs in South America. Pichia A large, apparently polyphyletic genus of yeasts (family SACCHAROMYCETACEAE). Cells are spheroidal, ellipsoidal or elongate; vegetative reproduction occurs by multilateral budding. Pseudomycelium and, to a limited extent, true mycelium may be formed. Arthrospores may be formed by some species. Species are homothallic or heterothallic. Asci are usually dehiscent. Ascospores: bowler-hat-shaped, Saturn-shaped, hemispheroidal, or spheroidal, smooth-surfaced, usually 1–4 per ascus. Sugars may or may not be fermented; NO3
is not assimilated. More than 56 species are recognized; type species: P. membranaefaciens. Several species have anamorphs in the form-genus Candida: e.g. the anamorph of P. burtonii is C. variabilis (and Trichosporon variabile), that of P. guilliermondii is C. guilliermondii, that of P. membranaefaciens is C. valida, etc. Pichia species are found in a wide range of habitats: e.g. tunnels and frass of wood-boring beetles, tree exudates, pickling brines, tanning liquors, grain and flour (e.g. P. farinosa), wine (e.g. P. carsonii [formerly P. vini ], P. membranaefaciens), naturally fermented apple juice (e.g. P. delftensis), cacti (e.g. P. cactophila, P. opuntiae), human skin, faeces, etc. [Book ref. 100, pp. 295–378.] (See also ALCOHOL OXIDASE, ALCOHOLIC FERMENTATION, BEER SPOILAGE, CIDER, METHYLOTROPHY, WINE SPOILAGE.) Pichinde virus See ARENAVIRIDAE. pickling A traditional method of FOOD PRESERVATION in which the pH is lowered either by direct addition of acid (e.g. VINEGAR, LACTIC ACID) or by a LACTIC ACID FERMENTATION of the food; cabbage (see SAUERKRAUT), cucumbers and olives are often preserved by fermentation [Book ref. 5, pp. 227–258]. Fresh vegetable material has a large and varied microflora, of which lactic acid bacteria form only a very small component; fermentation conditions must therefore specifically encourage the growth of the lactic acid bacteria. The vegetables are graded and washed (Spanish-style olives may be treated with NaOH to remove the bitter phenolic glucoside oleuropein), and salt is added; the salt extracts the sugar-containing juices, encouraging the growth of the lactic acid bacteria (mainly Lactobacillus brevis, L. plantarum and Pediococcus pentosaceus in the case of

olives and cucumbers – cf. SAUERKRAUT). [Lactic acid bacteria in vegetable fermentations: Food Mic. (1984) 1 303–313.] Fermentative yeasts may also be present; these may ferment any sugars remaining after the lactic acid bacteria have been inhibited by acidity. The combination of salt, anaerobiosis and low pH serves to discourage the growth of undesirable organisms. Microbial spoilage of pickled vegetables may be due e.g. to oxidative pectinolytic moulds and yeasts which cause softening of the vegetable tissue; these organisms form a surface film unless precautions are taken to exclude air. Oxidative yeasts may also metabolize lactic acid and hence reduce acidity, allowing the subsequent growth of other spoilage organisms. Spoilage bacteria (e.g. coliforms, clostridia) tend to grow when the pH is too high and/or the salt concentration too low; they can cause softening, off-flavours and odours, and/or the formation of gas pockets within the vegetable (called ‘bloater damage’ in cucumbers, ‘fisheye spoilage’ in olives). picodnaviruses Rejected name for the PARVOVIRIDAE. a-picolinic acid Pyridine 2-carboxylic acid, a toxin produced by Pyricularia oryzae. (See also BLAST DISEASE and PIRICULARIN.) Picornaviridae A family of small, ssRNA-containing VIRUSes in which the icosahedral virion (ca. 22–30 nm diam.) is naked and ether-resistant. Most picornaviruses have a narrow host range, and some are important pathogens of man and animals; transmission generally occurs mechanically. The family includes four genera: APHTHOVIRUS, CARDIOVIRUS, ENTEROVIRUS and RHINOVIRUS; within the genera, species are distinguished by their susceptibility to specific neutralizing antibodies. Some picornaviruses are currently not classified into genera; these include equine rhinovirus types 1 and 2, and insect picornaviruses such as cricket paralysis virus, Drosophila C virus and Gonometa virus. Possible picornaviruses include ‘unclassified small RNA viruses of invertebrates’: e.g., bee acute paralysis virus, bee slow paralysis virus, bee virus X, black queen cell virus, Drosophila P and A viruses, FLACHERIE virus and SACBROOD virus. [Review of small RNA viruses of insects: JGV (1985) 66 647–659.] Virion structure. The capsid comprises 60 subunits, a subunit consisting of one molecule each of the 4 major capsid polypeptides (VP1–VP4); portions of VP1, VP2 and VP3 are exposed at the virion surface, while VP4 is probably internal and may be associated with the RNA. [Virion structure in polioviruses: Science (1985) 229 1358–1365, and in rhinoviruses: Nature (1985) 317 145–153.] The RNA genome is a single molecule of linear positive-sense ssRNA (MWt ca. 2.5 ð 106 ) which is polyadenylated at its 30 end and covalently linked at its 50 end to a virus-encoded protein, VPg. In cardioviruses and aphthoviruses (but not in enteroviruses or rhinoviruses) the RNA contains a poly(C) tract near the 50 end, the length of which varies with strain. [Poly(C) secondary structure in aphthoviruses: JGV (1985) 66 1919–1929.] Replication cycle. Virus replication occurs in the host cell cytoplasm. Infection begins when a virion attaches to receptors in the host cell plasma membrane; in e.g. poliovirus type 1 and mouse Elberfeld virus, entry into the host cell apparently occurs by endocytosis, and uncoating apparently occurs in endosomes and/or lysosomes [JGV (1985) 66 483–492]. In polioviruses, translation of the viral RNA is initiated at one site near the 50 end of the RNA, resulting in the formation of a polyprotein; the polyprotein is initially cleaved, during translation, into three precursor proteins (P1, P2 and P3), each of which undergoes further cleavage. P1 gives rise to 1A, 1B, 1C and 1D (capsid polypeptides); P2 gives rise to 2A, 2B (a host-range determinant), and 2C (involved in RNA synthesis); P3 undergoes 586

pili intramolecular self-cleavage to form 3A, 3B (VPg), 3C (a protease which carries out most of the proteolytic cleavages), and 3D (an RNA polymerase which can elongate nascent RNA chains on an RNA template). [Nomenclature of picornavirus proteins: JV (1984) 50 957–959.] In contrast to polioviruses, aphthoviruses have two distinct translation initiation sites [JGV (1985) 66 2615–2626]. Replication of the RNA genome is associated with the smooth endoplasmic reticulum; (
)-strand synthesis may involve a primer formed by hairpin folding of the (C)-strand template, resulting in a product up to twice the length of the genome (at least in vitro) [JV (1986) 58 790–796]. Virus assembly is preceded by cleavage of P1 to form an immature 5S protomer containing VP0, VP1 and VP3. The immature protomers become associated with an RNA genome to form a provirion. During maturation most or all of the VP0 molecules are cleaved to form VP2 and VP4. The mature virions are eventually released by host cells lysis. (Some picornaviruses – e.g. hepatitis A virus – can cause non-lytic infections.) Most picornaviruses can be propagated in cell cultures. Infected cells undergo drastic changes in their macromolecular metabolism: the rate of RNA synthesis declines shortly after infection, and cellular protein synthesis is inhibited soon after. [Review of inhibition of protein synthesis: Book ref. 150, pp. 177–221.] Characteristic CPEs generally develop in the infected cells: e.g., accumulation of chromatin on the inside of the nuclear envelope; appearance of membranous vesicles in the cytoplasm; formation of crystalline arrays of virions in the cytoplasm; alterations in membrane permeability leading to shrivelling of the cell; etc. picornaviruses Viruses of the PICORNAVIRIDAE. picric acid (2,4,6-trinitrophenol) An antimicrobial agent (see PHENOLS), a fixative (see e.g. BOUIN’S FLUID), and a DYE. piedra See BLACK PIEDRA and WHITE PIEDRA. Piedraia A genus of fungi of the DOTHIDEALES (anamorph: Trichosporon). (See BLACK PIEDRA.) piericidin An antibiotic, produced by Streptoverticillium mobaraense, which acts as a RESPIRATORY INHIBITOR in mitochondrial and bacterial ELECTRON TRANSPORT CHAINS (although intact cells may be impermeable and hence insensitive to piericidin); the (non-covalent) binding site(s) and mechanism of action of piericidin are apparently similar to those of ROTENONE. pif A locus in the F PLASMID associated with the inability of certain phages (e.g. T7) to replicate in cells containing the F plasmid. (pif D phage-inhibitory function.) (See also FEMALESPECIFIC PHAGE.) pig bel Syn. ENTERITIS NECROTICANS. pig diseases (a) Bacterial diseases: see e.g. EPERYTHROZOONOSIS, FOOT-ROT, GLASSER’S DISEASE, GREASY PIG DISEASE, OEDEMA DISEASE, PARATYPHOID FEVER (sense 2), SWINE DYSENTERY, SWINE ERYSIPELAS, TULARAEMIA. (b) Viral diseases: see e.g. AFRICAN SWINE FEVER, AUJESZKY’S DISEASE, FOOT AND MOUTH DISEASE, INCLUSION BODY RHINITIS, PARVOVIRUS, SWINE FEVER, SWINE INFLUENZA, SWINE POX, SWINE VESICULAR DISEASE, TALFAN DISEASE, TESCHEN DISEASE, TRANSMISSIBLE GASTROENTERITIS, VESICULAR EXANTHEMA, VESICULAR STOMATITIS, VOMITING AND WASTING DISEASE. pigeonpox virus See AVIPOXVIRUS. pil genes The designation of genes which encode type IV FIMBRIAE in various Gram-negative bacteria – e.g. Neisseria gonorrhoeae and Pseudomonas aeruginosa; for example, in N. gonorrhoeae, pilC encodes the terminal adhesin, pilE encodes

the major subunit (see also ANTIGENIC VARIATION), and pilQ is a which is stabilized by an outer membrane lipoprotein encoded by pilP. Pilaira A genus of fungi (order MUCORALES) which occur on the dung of herbivores. The long, positively phototropic sporangiophore bears a single non-projectile sporangium which, on maturity, becomes adhesive. (cf. PILOBOLUS.) pileate (mycol.) Having a PILEUS. pileus The structure on which the spore-bearing tissue is carried in the sexually-derived fruiting bodies of certain basidiomycetes and ascomycetes. Examples include the entire lamella-bearing structure (‘cap’) carried by the stipe in mushroom-shaped basidiocarps; the corky or leathery, non-stipitate fruiting bodies formed by certain wood-rotting fungi; and the ridged and pitted stipe-borne cylindrical structures of the morels (Morchella spp). pili (singular : pilus) (1) (conjugative pili; sex pili) Elongated or filamentous, proteinaceous, plasmid-encoded structures which extend from the surface of those (Gram-negative) bacteria which contain an (expressed) CONJUGATIVE PLASMID. Some types of pili have been shown to play an essential role in CONJUGATION (sense 1b), and it is generally believed (though not proven) that all pili have essential roles in conjugation. (cf. FIMBRIAE; SPINA; FLAGELLUM.) Commonly, only a few pili (sometimes only one) occur on a given donor cell (cf. FIMBRIAE). At least some types of pili appear to be retractable, but the mechanism of retraction is unknown. In general, thin, flexible pili mediate so-called ‘universal’ conjugation systems, i.e. systems in which conjugation can occur equally well within a body of liquid (e.g. broth) or on a moist (but not submerged) solid surface (e.g. an agar plate or membrane filter). Rigid pili often mediate ‘surface-obligatory’ mating, i.e. conjugation which occurs at a negligible frequency in liquid media but which may occur at high frequency on a moist, non-submerged solid surface. Thick, flexible pili may mediate in either ‘surface-preferred’ mating (in which conjugal transfer occurs more readily on solid surfaces than within liquids) or universal mating. [Surface mating systems in Escherichia coli: JB (1980) 143 1466–1470; surface mating systems in Pseudomonas spp: JGM (1983) 129 2545–2556.] F pili (encoded by the F PLASMID) are thin, flexible filaments that are one to several micrometres in length, ca. 8 nm in diameter; each F-pilus has an axial channel, ca. 2 nm diameter, with a hydrophilic lumen. It has been assumed that the base of a pilus is associated with an ADHESION SITE or similar structure. F pili are composed mainly or solely of a single type of subunit, pilin; the 70-amino acid pilin molecule is a single polypeptide containing one residue of D-glucose and two phosphate residues. The way in which the pilin subunits are assembled to form the pilus is not known. In one model, rings of five pilin subunits are stacked along the axis of the pilus, each ring being rotated 29° relative to the previous ring. In a second model, the pilin molecules are arranged helically. [Structure of F-pilin and a model for the organization of pilin subunits in the F pilus: Mol. Microbiol. (1997) 23 423–429.] Bacteriophages which can bind to F pili include f1, fd and M13 (see INOVIRUS), and MS2 and Qb (see LEVIVIRIDAE). (See also ANDROPHAGE.) (Note that the term pilin is also used to refer to the subunits of other types of pili – and also to the subunits of fimbriae.) F-like pili are serologically similar or identical to F pili, and they bind similar types of phage. They are encoded e.g. by the colicin plasmids ColV and ColI-K94. SECRETIN

587

Pilimelia bacteria, but were poorly active against Gram-positive species. Modern pine fluids (with RW coefficients of ca. 3–5) typically contain phenolics (e.g., 2-phenylphenol, 4-chloro-3,5-xylenol) together with e.g. terpineol (an antimicrobial constituent of pine oil) and a solubilizing agent, e.g., potassium ricinoleate; these fluids are active against both Gram-negative and Gram-positive bacteria. The activity of at least one pine fluid against Pseudomonas aeruginosa is greatly increased at temperatures above 30° C [Book ref. 13, pp. 85–90]. The recommended maximum dilution of a pine fluid is 20 times its RW coefficient. pink-eye (pinkeye) (1) Syn. CONJUNCTIVITIS. (2) An acute contagious conjunctivitis caused by Haemophilus aegyptius. (3) Syn. INFECTIOUS KERATITIS (of cattle). Pinnularia See DIATOMS. pinocytosis The ingestion, by various types of eukaryotic cell (e.g. amoebae, macrophages), of minute droplets of fluid; in pinocytosis (as in PHAGOCYTOSIS) a small region of the CYTOPLASMIC MEMBRANE invaginates and is subsequently pinched off to form a closed, intracellular membranous sac (pinocytotic vesicle, pinosome) containing the ingested fluid. In one form of pinocytosis (fluid-phase pinocytosis) pinocytotic vesicles are formed continually at non-specific sites in the cytoplasmic membrane – samples of extracellular fluid being taken randomly; such vesicles often fuse with LYSOSOMES. Receptor-mediated pinocytosis (D absorptive pinocytosis) is a selective process in which specific types of macromolecule (or e.g. virus particle) are taken up. The macromolecules bind to specific receptors located at the outward-facing surface of the cytoplasmic membrane, groups of such receptors occurring in discrete regions of the cytoplasmic membrane known as coated pits; a coated pit bears on its inner (i.e., cytoplasmic) surface a characteristic array of molecules of the fibrous protein clathrin (MWt ca. 215000). Clathrin occurs in propeller-shaped (‘three-legged’) trimeric units (triskelions) which assemble into pentagons and hexagons, forming a polygonal network which comprises the cytoplasmic face of the coated pit. (Often, bundles of ACTIN microfilaments – stress fibres – occur in the cytoplasm beneath a coated pit.) Following receptor-mediated binding of macromolecules to a coated pit, the coated pit region invaginates and eventually pinches off to form a pinocytotic vesicle – the outer (cytoplasm-facing) surface of the vesicle being covered by a lattice-like network of clathrin; the vesicle, enclosed within its clathrin ‘cage’, is called a coated vesicle. Before fusing with e.g. a lysosome, a coated vesicle must have its clathrin removed in an ATP-dependent process. [Enzymatic recycling of clathrin from coated vesicles: Cell (1986) 46 5–9.] pinosome See PINOCYTOSIS. pinosylvin 3,5-Dihydroxy-trans-stilbene: an antifungal compound formed by many species of pine (Pinus); it appears to be at least partly responsible for the relative resistance of pine heartwood to fungal attack. (See also TIMBER PRESERVATION.) pinta (mal del pinto; syn. spotted sickness) A chronic infectious human disease caused by Treponema carateum; it occurs in Central and South America. Symptoms: spots or patches of abnormally pigmented or depigmented skin; other tissues are rarely affected. Chemotherapy: e.g. penicillins. pInv plasmid See EIEC. pionnotes In Fusarium spp: a flat spore mass which has a fat-like or greasy appearance. pipemidic acid See QUINOLONE ANTIBIOTICS. Piptocephalis A genus of fungi (order ZOOPAGALES) which are parasitic on other fungi, often other zygomycetes. The vegetative hyphae develop extracellularly on the host – from which

I-like pili resemble F pili morphologically but they differ serologically and they bind different phages – e.g. If1 and If2 (see INOVIRUS). They are encoded e.g. by the ColIb-P9 plasmid. Short, rigid, nail- or thorn-like pili are encoded e.g. by IncN enterobacterial plasmids and Pseudomonas IncP-7 plasmids. The precise role of the pilus is as yet unknown – see CONJUGATION. The currently favoured model (at least for the F pilus and related pili) is one in which the pilus makes initial contact with the recipient and then retracts to draw donor and recipient into wall-to-wall contact. Evidence supportive of this model includes the demonstration that a mutant donor with a temperature-dependent block in DNA transfer can achieve wall-to-wall contact with a recipient independently of DNA transfer; DNA transfer can occur subsequently at the permissive temperature, thus excluding the need for an extended pilus as a conducting tube for DNA [JB (1985) 162 584–590]. The role of the short, rigid pili encoded e.g. by IncN plasmids remains unknown. (2) Collectively, pili (sense 1, above) and FIMBRIAE. Use of the term in this way should be discouraged owing to the confusion it causes (see FIMBRIAE for rationale). Pilimelia A genus of keratinophilic bacteria (order ACTINOMYCETALES, wall type II) which occur e.g. in soil. The organisms resemble Actinoplanes spp but differ e.g. in that they form parallel chains of rod-shaped zoospores in spherical or cylindrical sporangia. Type species: P. terevasa. [Book ref. 73, pp. 65–66.] pilin See FIMBRIAE and PILI. Pillotina See SPIROCHAETALES. Pilobolaceae See MUCORALES. Pilobolus A genus of fungi (order MUCORALES) which occur on the dung of herbivores. In Pilobolus spp a single sporangium is carried on a subsporangial vesicle at the distal end of each long, positively phototropic sporangiophore; the (non-dehiscent) sporangium is propelled from the sporangiophore by a jet of liquid which escapes, explosively, from the subsporangial vesicle. (cf. PILAIRA.) Pilophorus A genus of LICHENS (order LECANORALES); photobiont: a green alga. Erect pseudopodetia (see PSEUDOPODETIUM) – which may bear terminal, convex, black apothecia – arise from a granular primary thallus which may be evanescent; cephalodia are generally present. Species grow e.g. on rocks, particularly in mountainous regions. pilot protein A protein which is believed to aid the transfer of DNA from a donor cell to a recipient during bacterial CONJUGATION (sense 1b) or from a bacteriophage virion to a host cell during certain types of phage infection. pilus See PILI. pimaricin (natamycin; tennecetin) A MYCOSAMINE-containing tetraene POLYENE ANTIBIOTIC produced by Streptomyces natalensis. It is used e.g. in the treatment of mycotic keratitis and as an antifungal food preservative e.g. in sausages, fruit juices, cheese etc; it can be inactivated by enzymes produced by certain moulds (e.g. Aspergillus flavus). pin gene See RECOMBINATIONAL REGULATION. pine diseases Diseases of pine trees (Pinus spp) include BLISTER RUST and PITCH CANKER. Pine wilt may be caused by a species of the fungus Ceratocystis (vector: bark beetles) or by the nematode Bursaphelenchus xylophilus (vector: the pine sawyer). (See also TREE DISEASES.) pine disinfectants (pine fluids) DISINFECTANTS which include certain volatile oils obtained synthetically or by steam-distillation of pine wood. The early pine fluids were made by solubilizing pine oil with soap; they were active mainly against Gram-negative 588

plague vesicle) appears on each side of the plug; the cytoplasmic membrane thus remains continuous from one cell to another. (cf. PLASMODESMA.) A secondary pit connection may develop between two cells which have become juxtaposed. (See also CHOREOCOLAX.) pitch canker A disease of pine trees (Pinus spp) caused by Fusarium moniliforme var. subglutinans; symptoms include dieback of terminal and lateral branches, and the formation of CANKERS characterized by a copious flow of resin. Pitelka convention A system for numbering the microtubular triplets in a kinetosome. Looking at a cross-section of a ciliary kinetosome from the direction of the interior of the cell, the triplet associated with the ribbon of POST-CILIARY MICROTUBULES is designated number 5; the numbering sequence is clockwise – as in the GRAIN CONVENTION. Pithomyces See HYPHOMYCETES; see also SPORIDESMINS. pitted keratolysis A human skin disease characterized by focal erosion of the stratum corneum, usually on the soles and heels of the feet; it appears to be caused by an organism resembling Dermatophilus congolensis. Pittsburg pneumonia agent Legionella micdadei. pityriasis nigra (tinea nigra) A benign superficial human dermatomycosis in which brownish or black macules are formed (usually on the palms of the hands). Causal agents: Exophiala werneckii (D Cladosporium werneckii ) or Stenella araguata (D Cladosporium castellanii ). pityriasis versicolor (tinea versicolor) A mild, chronic, superficial human dermatomycosis caused by Malassezia furfur (‘Pityrosporum orbiculare’); flat or slightly raised, scaly, brownish or fawn spots (which gradually enlarge and coalesce) develop mainly on the chest, back, arms and neck. Lesions may fluoresce greyish-yellow under Wood’s lamp. Pityrosporum Syn. MALASSEZIA. pivampicillin See PENICILLINS. Pixuna virus See ALPHAVIRUS. ¨ P–K test See PRAUSNITZ–KUSTNER TEST. PKA See CYCLIC AMP. PKC kinase See CHEMOKINES. PKD PROLIFERATIVE KIDNEY DISEASE. PKDL POST-KALA-AZAR DERMAL LEISHMANIASIS. pKM101 See SOS SYSTEM and AMES TEST. PKR kinase See INTERFERONS. Placidiopsis See VERRUCARIALES. placoderm desmid See DESMIDS. placodioid (placoid) (lichenol.) Refers to a crustose thallus which is generally circular in outline with radial lobes at the periphery. placoid Syn. PLACODIOID. Plagiacantha See RADIOLARIA. Plagonium See RADIOLARIA. plague An acute infectious disease which primarily affects rodents but which can be transmitted to man; the causal agent is Yersinia pestis (see also VIRULON). Before the availability of antibiotic therapy, epidemics and pandemics of plague caused enormous loss of life; for example, an outbreak in Europe during the 14th century (the ‘Black Death’) involved ca. 25 million deaths. The World Health Organization has recently recognized plague as a ‘re-emerging disease’. An epidemic of human plague is commonly preceded by an epizootic among urban rats; Rattus rattus populations are rapidly decimated in such epizootics, but wild rodents in rural or wooded areas are less susceptible and provide a reservoir of infection.

nutrients are abstracted by means of haustoria. Asexually derived spores are formed in merosporangia carried on (typically) deciduous ‘head cells’ at the distal ends of dichotomously branched sporangiophores; each merosporangium contains one or a few spores. Most species are apparently homothallic. Piptoporus A genus of lignicolous fungi of the APHYLLOPHORALES (family Polyporaceae) which form typically annual, non-stipitate basidiocarps having a whitish or pale brown, corky, dimitic, non-xanthochroic context; the bracket-type basidiocarp has a porous hymenophore on the underside. P. betulinus (‘razor-strop fungus’) is saprotrophic and parasitic on birch (Betula); the upper surface of the basidiocarp has a thin, pale brown, separable outer layer, and the lower porous surface is whitish. Basidiospores: colourless, cylindrical, ca. 5 ð 2 µm. (See also BROWN ROT and TIMBER SPOILAGE; cf. POLYPORUS.) pir gene See R6K PLASMID. Pirella See PASTEURIA. piricularin (pyricularin) A toxin produced by Pyricularia oryzae (see BLAST DISEASE). Piricularin is toxic to the fungus itself, but P. oryzae produces a copper-containing ‘piricularin-binding protein’ which complexes the toxin and renders it non-toxic for the fungus without affecting its toxicity for the rice plant. CHLOROGENIC ACID can complex piricularin and inactivate it. Piromonas A genus of fungi found in the RUMEN. piroplasm (1) A member of the PIROPLASMASINA. (2) The intraerythrocytic stage of Theileria spp. Piroplasmasina A subclass of protozoa (class SPOROZOASIDA) in which the APICAL COMPLEX is less well developed than in other members of the Sporozoasida, and in which the conoid is absent; reproduction occurs asexually (by binary fission or schizogony) and sexual reproduction occurs in at least some species. Motility involves e.g. cell flexion. Species are parasitic in the erythrocytes (and other cells) of vertebrates but do not form pigment from host cell haemoglobin (cf. HAEMOSPORORINA). Piroplasms are heteroxenous and are transmitted by ticks. Genera: BABESIA, Dactylosoma, THEILERIA. Piroplasmea A class of parasitic protozoa classified within the subphylum Sarcomastigophora [JP (1964) 11 7–20] and subsequently, as the subclass PIROPLASMASINA, in the class SPOROZOASIDA. Piroplasmia A subclass of protozoa [JP (1980) 27 37–58] equivalent to the PIROPLASMASINA. Piry virus A virus (genus VESICULOVIRUS) antigenically related to VSV. pisatin An isoflavonoid PHYTOALEXIN (3-hydroxy-7-methoxy40 ,50 -methylenedioxychromanocoumaran) produced by the pea plant (Pisum sativum). Some isolates of Nectria haematococca which are pathogenic for P. sativum can tolerate pisatin and can ‘detoxify’ the phytoalexin by demethylating it. Pisolithus A genus of saprotrophic or mycorrhizal fungi (order SCLERODERMATALES). P. arhizus (D P. tinctorius) forms large, club-shaped, partly hypogean, ochre to brownish basidiocarps (up to ca. 25 cm high) which contain closed pockets or chambers (peridioles) that eventually desiccate and crumble to release their content of basidiospores; this organism forms mycorrhizal associations with various trees and can apparently enhance the growth of e.g. pine trees under conditions which are normally suboptimal for their growth. pit connection In many multicellular red algae: a structure located between two adjacent cells. A primary pit connection forms between two daughter cells during cell division: a central hole in the intercellular septum becomes blocked by a plug of electron-dense material, and a plug cap (formed from a flattened 589

plague

PLAGUE: areas where endemic plague is known to have persisted near the end of the 20th century. Areas in black are regions in which there are populations of wild rodents that carry the plague bacillus. Reproduced from Medical Microbiology 14th edition, Figure 36.1, page 406, David Greenwood, Richard Slack & John Peutherer (eds) (1992) copyright Churchill Livingstone (Harcourt Publishers Ltd, Edinburgh) (ISBN 0-443-04256-X) by courtesy of the author, Dr J. D. Coghlan, and with permission from the publisher.

antigen (see YERSINIA). PCR-based diagnosis (amplification of a sequence of the Y. pestis caf1 gene) under field conditions in Madagascar was found to be less sensitive than culture or serology and was not recommended [JCM (2000) 38 260–263]. [Rapid mAb/F1-based test for bubonic/pneumonic plague: Lancet (2003) 361 211–216.] Chemotherapy: e.g. tetracyclines, streptomycin or chloramphenicol. Vaccines containing either inactivated virulent cells or live avirulent cells may offer short-term protection. [Molecular and cell biology aspects of plague: PNAS (2000) 97 8778–8783.] Endemic plague persists in various regions of the world (see figure) and, significantly, transferable (plasmid-mediated) multidrug resistance has been reported in Yersinia pestis [NEJM (1997) 337 677–680]. [Dynamics of plague in the rat population, and transmission of the disease to humans: Nature (2000) 407 903–906. Bubonic plague (a metapopulation model of a zoonosis): Proc. RSLB (2000) 267 2219–2230.] planachromat See ACHROMAT. planapochromat See APOCHROMAT. Planctomyces A genus of planktonic freshwater bacteria. Cells: cocci, or coccoid to pear-shaped forms, ca. 0.3–2.0 µm, which develop non-prosthecate, bristle-like appendages when mature; the cell wall contains no peptidoglycan. Reproduction occurs by budding. Types species: P. bekefii. Other species include e.g. P. guttaeformis and P. stranskae [IJSB (1984) 34 470–477];

Transmission from rat to rat, and from rat to man, occurs via the bite of the rat flea (especially Xenopsylla cheopsis); the gut of an infected flea becomes blocked by plague bacilli which are regurgitated into the next bite. Person-to-person transmission may occur via the human flea, Pulex irritans (a less effective vector), or, in pneumonic plague, by droplet infection. Plague bacilli have been reported to occur in the throats of symptomless human carriers. In man, plague occurs in three clinical forms. In bubonic plague, the commonest form, the incubation period is 2–6 days; onset is sudden, with fever, prostration, haemorrhages and the development of buboes: swollen, inflamed, necrotic lymph nodes. Septicaemia may result in e.g. meningitis or secondary pneumonia. (cf. PESTIS MINOR.) In primary septicaemic plague (incubation period: 2–6 days) there is a sudden onset with high fever, haemorrhages, vomiting and bloody diarrhoea, but no buboes. Primary pneumonic plague results from infection by inhalation (incubation period: 2–3 days). There is high fever, prostration, severe pneumonia and frequently delirium and coma; the sputum contains large numbers of plague bacilli. Mortality rates in untreated cases: e.g. bubonic plague 25–50%; pneumonic and septicaemic plague ¾100%; early antibiotic therapy is associated with significantly lower mortality. Lab. diagnosis. Demonstration of the pathogen in fluid from buboes, blood, CSF or sputum (by microscopy and/or culture) and/or serology for antibodies against the F1 (‘fraction 1’) 590

plant viruses the latter bearing elongated sporangia, singly or in groups, each sporangium containing a serially-arranged pair of spores; liberated spores become motile (flagellated). Type species: P. longispora. [Book ref. 73, pp. 111–112.] Planococcus A genus of Gram-positive, asporogenous, catalasepositive, chemoorganotrophic, aerobic bacteria which occur as marine saprotrophs. Cells: cocci (each having 1–3 flagella) which occur in pairs and tetrads; the cell wall contains no teichoic acids. A yellow-brown pigment is formed. Carbohydrates are not utilized. Growth occurs e.g. on nutrient agar containing 12% NaCl. GC%: ca. 39–51. Species: P. citreus (type species) and P. halophilus. planofluorite See FLUORITE OBJECTIVE. planogamete A motile GAMETE. Planomonospora A genus of bacteria (order ACTINOMYCETALES, wall type III; group: maduromycetes) which occur in soil. The organisms form branching substrate and aerial mycelium, the latter bearing rows of parallel, elongated sporangia, each sporangium being attached at one end to the hypha; each sporangium contains one spore which becomes motile (flagellated) after release. Type species: P. parontospora. [Book ref. 73, 112–113.] planospore A motile SPORE. plant viruses VIRUSes which can infect and replicate in plants. (cf. VIROID; VIRUSOID.) Commonly, plant viruses show a low degree of host specificity, and some can also replicate in insects. Infection of a plant by a given virus may be systemic – spreading rapidly via the phloem (or occasionally xylem) or slowly from cell to cell via plasmodesmata – or may remain localized at the site of infection. (Spread is apparently a virus-specific function involving virus-encoded or virus-induced proteins [review: AVR (1984) 29 313–364].) Infection may be symptomless (silent, ‘latent’), or may involve the development of symptoms ranging from mild to severe or lethal; symptoms, when present, often depend on the species and variety of the host plant, on the particular virus strain, and on environmental conditions, and may be affected by the presence of another virus or of a

‘P. gracilis’ has been excluded from the genus [IJSB (1984) 34 465–469]. plankter See PLANKTON. plankton Collectively, the microorganisms (chiefly microalgae and protozoa), small invertebrates (e.g. copepods and other small crustacea) and fish larvae etc which drift more or less passively in water currents within the pelagic zone of lakes, seas and other bodies of water; although many planktonic organisms are actively motile, even these organisms depend on water currents for significant amounts of displacement. The plant and plantlike components of plankton (including e.g. the photosynthetic flagellates) are referred to as phytoplankton, while the animal or animal-like components (including e.g. protozoa) are called zooplankton. An individual planktonic organism is called a plankter. Plankton, particularly phytoplankton, is important as the basis of the aquatic food chain; it is consumed by a range of invertebrates and by certain fish and whales. Microbial marine plankton includes e.g. DIATOMS, DINOFLAGELLATES, RADIOLARIA, members of the PRYMNESIOPHYCEAE and TINTINNINA, and certain foraminifera (e.g. GLOBIGERINA, GLOBIGERINOIDES). Microbial freshwater plankton includes e.g. CYANOBACTERIA, DESMIDS, DIATOMS, and members of the HELIOZOEA. Various schemes have been proposed for the classification of planktonic organisms according to size; thus, e.g. nannoplankton (D nanoplankton ) may include (depending on author) organisms which are less than 20 µm, less than 50 µm, 5–50 µm, 5–60 µm, or greater than 75 µm. Similarly, mesoplankton may include organisms of 0.5–1.0 mm, 0.2–2.0 mm, greater than 1.0 mm or 1–5 mm. (cf. NEKTON, NEUSTON; see also BLOOM.) Planktothrix A genus of gas-vacuolate CYANOBACTERIA. [Variation in gas vesicle genes: Microbiology (2000) 146 2009–2018.] Planobispora A genus of bacteria (order ACTINOMYCETALES, wall type III; group: maduromycetes) which occur in soil. The organisms form branching substrate and aerial mycelium,

PLANT VIRUSES: basic characteristics Genome

Envelope

Nucleocapsid morphology

Virus group (or unclassified virus)a

dsDNA ssDNA dsRNA






isometric paired isometric particles isometric

ssRNA ssRNA monopartite

C

š rod-shaped

caulimoviruses geminiviruses plant reoviruses (Reoviridae), rice ragged stunt virus, some cryptic viruses plant rhabdoviruses (Rhabdoviridae), tomato spotted wilt virus




isometric

monopartite




rod-shaped or filamentous

bipartite




isometric

bipartite tripartite tripartite multipartite







rod-shaped or filamentous š isometric š rod-shaped filamentous

a

luteoviruses, maize chlorotic dwarf virus, sobemoviruses, tobacco necrosis virus, tombusviruses, tymoviruses carlaviruses, closteroviruses, potexviruses, potyviruses, tobamoviruses comoviruses, dianthoviruses, nepoviruses, pea enation mosaic virus, velvet tobacco mottle virus furoviruses?, hordeiviruses (some strains), tobraviruses bromoviruses, cucumoviruses, ilarviruses alfalfa mosaic virus, hordeiviruses (some strains) rice stripe virus group

See separate entries for details. 591

Plantago mottle virus SATELLITE VIRUS or SATELLITE RNA. Virus-infected plants may exhibit one or more of the following symptoms: CHLOROSIS, COLOUR-BREAKING, curling or distortion of leaves, ENATIONS, GALL-formation, MOSAIC, MOTTLE, NECROSIS, RINGSPOT, ROSETTEformation, STREAK, stunting of growth, TOP NECROSIS, VEIN BANDING, VEIN CLEARING, VIRESCENCE, yellowing (see YELLOWS), etc. (Plant structures which are fully matured at the time of infection may fail to develop symptoms.) Transmission of many plant viruses can occur mechanically – e.g. by contact between plants or by contamination of a plant with sap from an infected plant (present e.g. on pruning implements, hands etc); in the laboratory mechanical transmission can often be achieved by rubbing the leaves of a plant with a virus preparation – often mixed with a mild abrasive. Some viruses can be transmitted via soil, via seeds or tubers, or by grafting (e.g. from an infected stock to an uninfected scion). Many plant viruses can be transmitted only by specific VECTORS such as sap-sucking or biting insects, mites, nematodes, fungi, or parasitic plants such as the dodder (Cuscuta spp). (See CIRCULATIVE TRANSMISSION and NON-CIRCULATIVE TRANSMISSION.) Identification of a plant virus is seldom possible from symptoms exhibited by infected plants in the field, but may be achieved e.g. by light or electron microscopy of infected tissues (many viruses induce characteristic inclusion bodies in infected cells), by inoculation of the virus into a range of suitable DIFFERENTIAL HOSTS, and/or by serological tests; plant viruses are generally effective immunogens, and specific antibodies against a known virus can be raised in animals and used for the identification of an unknown virus (e.g. by ELISA, IMMUNOELECTRON MICROSCOPY, IMMUNOSORBENT ELECTRON MICROSCOPY, precipitin tests, etc). A plant virus may be assayed e.g. using a LOCAL LESION host. Cultivation in vitro of many plant viruses can be achieved in plant protoplasts derived e.g. from cell suspension cultures or mesophyll tissue of leaves [AVR (1984) 29 215–262] or from shoot cultures [e.g. of potatoes: JGV (1985) 66 1341–1346]. Control of virus diseases of plants may involve any of various preventive measures: e.g. use of virus-free seed (obtained e.g. by meristem culture), control of vector populations, ROGUING, removal of volunteer plants or weeds in which the virus may overwinter, selection of resistant or tolerant plant cultivars, etc. Once a plant is infected with a virus there is no effective chemical treatment; however, certain viruses can be inactivated by subjecting the infected plant (or seeds in the case of seedborne viruses) to air temperatures of 30–35° C (for days or weeks), to water immersion at ca. 40 or 50° C for shorter periods, etc (‘thermotherapy’). [Heat treatment of lettuce seeds carrying lettuce mosaic virus: Ann. Appl. Biol. (1985) 107 137–145.] Nomenclature and classification. Individual plant viruses are generally given names based on the common, first-recognized, or most important host plant, and on the main symptom(s) produced by the virus in that plant under natural conditions. (Examples: apple chlorotic leafspot virus; barley yellow dwarf virus.) In the majority of plant viruses the virus genome consists of RNA which is often segmented and sometimes distributed between two or more separate virus components (see MULTICOMPONENT VIRUSES). On the basis of the nature of the genome, shape of the virus particle(s), presence or absence of an envelope, etc, plant viruses are classified into ‘groups’ (see table); the name of a group is commonly a sigla derived e.g. from the name of the type virus (e.g. caulimoviruses from cauli flower mosaic virus). A few plant viruses are related to certain animal viruses and are included in animal virus classification schemes: see

e.g. REOVIRIDAE VIRUS.)

and

RHABDOVIRIDAE.

(cf.

TOMATO SPOTTED WILT

Plantago mottle virus See TYMOVIRUSES. Plantago severe mottle virus See POTEXVIRUSES. Plantago virus See CAULIMOVIRUSES. Plantago virus X See POTEXVIRUSES. plantar wart See PAPILLOMA. plantaricin S See BACTERIOCINS. plaque (1) A discrete, macroscopic or microscopic, usually circular region in a cell monolayer (see TISSUE CULTURE) or in a film or layer of bacterial growth (see LAWN PLATE) in which some or all of the cells have been lysed, or their growth has been strongly inhibited, as a result of the activity of a virus or other agent (e.g. BDELLOVIBRIO). In virology, it is generally assumed that each plaque develops following the replication of a single virion; thus, e.g., when the first-infected cell lyses, the progeny virions diffuse outwards, progressively infecting and lysing other cells until a visibly depopulated area (the plaque) is produced. Plaque characteristics – e.g. size, shape, nature of the margin – can be useful e.g. in identifying the infecting virus, or in determining whether or not a cell population is homogeneous in its susceptibility to the virus; thus, e.g., clear plaques (total cell lysis) on a lawn of susceptible bacteria are typically produced by virulent bacteriophages, while turbid plaques are characteristic of temperate phages – which lyse only some of the cells in the plaque area – and of non-lytic phages (see e.g. INOVIRIDAE). (2) (verb) To inoculate a lawn plate or cell monolayer with a virus suspension in order to obtain plaques (sense 1). (3) See DENTAL PLAQUE. (4) (med., vet.) A patch or flat lesion e.g. on skin or mucous membranes (see e.g. DOURINE). plaque assay A procedure for determining the PLAQUE TITRE of a given viral suspension. Bacteriophages. Log dilutions of the phage suspension are initially prepared, and a measured volume of a given dilution is added to a known volume of molten (ca. 45–46° C) semisolid agar containing an excess of sensitive bacteria; the whole is well mixed and poured onto a plate of solid nutrient agar, forming an upper layer 1–2 mm thick. An identical procedure is carried with each dilution; the plates are incubated at the growth temperature of the bacterium and subsequently examined for PLAQUES. Since each plaque is assumed to have been caused by a single phage, the plaque titre of the original phage suspension can be calculated from the volumes and dilutions used. Other viruses. Plaque assay can be carried out for other viruses if suitably sensitive monolayer cultures (see TISSUE CULTURE) are available. In one method, each of a number of monolayer cultures is drained of growth medium and inoculated with a known volume of one of a range of log dilutions of the viral suspension; the cultures are rocked to enable viruses to adsorb throughout the cell sheet. The monolayers are then overlaid with buffered growth medium in semi-solid purified agar, incubated, and subsequently examined for plaques. (The agar overlay inhibits the spread of viruses from the plaque areas.) plaque-forming unit (pfu) An entity – usually a virion, but also e.g. an ‘infectious centre’ (see ONE-STEP GROWTH EXPERIMENT) – which can give rise to a single PLAQUE under appropriate conditions. (See also EOP and PLAQUE TITRE.) plaque mutant Syn. PLAQUE-TYPE MUTANT. plaque-reduction assay See INTERFERONS. plaque titre The number of PLAQUE-FORMING UNITS per unit volume. plaque-type mutant (plaque mutant; plaque morphology mutant) A mutant virus which forms PLAQUES (sense 1) that differ from 592

plasmid environment does not select for the genetic diversity needed by species in more challenging environments [FEMS Reviews (1998) 22 255–275]; however, some intracellular bacteria (e.g. Chlamydia spp) are known to contain plasmids [see e.g. Microbiology (1997) 143 1847–1854]. Many plasmids encode product(s) and/or functions(s) which modify the phenotype of the host cell. Almost any feature may be encoded by plasmids, including e.g. resistance to particular ANTIBIOTIC(s) and/or HEAVY METAL(s) (see R PLASMID), and the synthesis of AGROCINS, BACTERIOCINS, GAS VACUOLES (e.g. in certain strains of Halobacterium), restriction endonucleases (see also PHAGE TYPING), SIDEROPHORES, toxins (see e.g. ANTHRAX TOXIN, ETEC) or virulence factors (see e.g. CROWN GALL and VW ANTIGENS). Some plasmid-encoded products alter the antigenic characteristics of a cell (see e.g. ANTIGEN GAIN), and some confer the ability to utilize particular substrate(s) (see e.g. LACTOSE PLASMID, OCT PLASMID, TOL PLASMID). One plasmid may counteract the effects of another; for example, the pSa plasmid can abolish the specific adherence properties of Agrobacterium strains which are due to the presence of the Ti plasmid [JGM (1983) 129 3657–3660]. (See also CRYPTIC PLASMID.) The presence of a plasmid within a cell may often be inferred from the cell’s phenotype: certain characteristics are commonly plasmid-specified. Whether or not a plasmid is present may be determined e.g. by gel ELECTROPHORESIS of a CLEARED LYSATE, or by treating the cells with certain agents that eliminate plasmids (see CURING sense 2) and observing for the loss of particular phenotypic properties. [Plasmid technology: Book ref. 177.] Some plasmids can promote their own intercellular transfer by CONJUGATION (sense 1b): see CONJUGATIVE PLASMID; some conjugative plasmids contain a TRANSFER OPERON which is DEREPRESSED for conjugal transfer. (See also EPIDEMIC SPREAD.) In addition to their own intercellular transfer, some conjugative plasmids can mobilize the host cell’s chromosome (or certain types of non-conjugative plasmid) for intercellular transfer (see CONJUGATION sense 1b). More than one type of plasmid can occur in a given cell; plasmids which have different modes of replication (see below) and of PARTITION are said to exhibit compatibility, i.e., they can co-exist stably in the same cell. Plasmids which have similar or identical replication/partition systems are incompatible, i.e., they cannot co-exist stably in the same cell; the phenomenon of incompatibility enables plasmids to be classified into a number of ‘incompatibility groups’ (Inc groups): see INCOMPATIBILITY. Plasmid replication. A plasmid controls its own replication, using the cell’s biosynthetic machinery to make any plasmidencoded proteins etc. that are needed; plasmid DNA REPLICATION requires various host proteins – commonly e.g. the product of the DNAB GENE, the DNAC GENE, the dnaE gene (D polC gene: see DNA POLYMERASE) and the dnaG gene (see PRIMASE) in Escherichia coli. (See also DNAA GENE.) Replication is not coupled to any specific stage or event in the CELL CYCLE, and in some plasmids it occurs throughout the cell cycle. Replication and PARTITION appear to be independent processes, although both can determine INCOMPATIBILITY. The rate-limiting step in replication is initiation, and the rate of initiation is controlled in ways that differ according to plasmid. In some plasmids the control of initiation involves constitutive synthesis of small, trans-acting ANTISENSE RNA molecules. Thus, e.g. in plasmid ColE1 control involves the synthesis of two, free (i.e. non-duplexed) strands of plasmid-encoded RNA, one

those formed by the wild-type virus in a population of sensitive cells. plasma (1) (in vivo) The fluid (non-particulate) part of blood. (2) (in vitro) Fluid obtained (e.g. by centrifugation) from blood which has been pre-treated with an ANTICOAGULANT. (cf. SERUM.) plasma cell (immunol.) An antibody-secreting cell that develops from a B LYMPHOCYTE on appropriate antigenic stimulation (see ANTIBODY FORMATION); plasma cells occur e.g. in the spleen and (particularly) in lymph nodes which are draining an infected site. In the earliest stage of the immune response the secreted antibodies are of the IgM class; however (for TD antigens), antibodies of other classes are secreted subsequently following class switching (see ANTIBODY FORMATION). Typical plasma cells are ovoid, ca. 10 ð 15 µm, with an offcentre nucleus which, when stained, may have a ‘clock-face’ or ‘cartwheel’ appearance due to the arrangement of chromatin. The (non-granular) cytoplasm contains a well-developed, ribosomerich endoplasmic reticulum (see also METHYL GREEN–PYRONIN STAIN). plasma clotting See FIBRIN; COAGULASE; ANTICOAGULANT. plasma membrane Syn. CYTOPLASMIC MEMBRANE. plasma volume extenders (for blood transfusion) See DEXTRANS. plasmagel See e.g. SARCODINA. plasmalemma Syn. CYTOPLASMIC MEMBRANE. plasmalogen A glycerophospholipid in which the glycerol bears a 1-alkenyl ether group. Plasmalogens occur e.g. in the cytoplasmic membrane in anaerobic bacteria. plasmasol See e.g. SARCODINA. Plasmaviridae (mycoplasma virus type 2 phages; L2 acholeplasmavirus group) A family of enveloped, pleomorphic MYCOPLASMAVIRUSES containing dsDNA. One genus: Plasmavirus; type species: BACTERIOPHAGE MV-L2. Other members: bacteriophage 1307 and possibly v1, v2, v4, v5 and v7. Plasmavirus See PLASMAVIRIDAE. plasmid In many types of prokaryotic and eukaryotic cell: a linear or covalently closed circular (ccc) molecule of DNA (q.v.) – distinct from chromosomal DNA, mtDNA, ctDNA or kDNA – which can replicate autonomously (i.e., independently of other replicons) and which is commonly dispensable to the cell; the term ‘plasmid’ is sometimes used to refer also to the dsRNA elements which occur in certain yeasts: see KILLER FACTOR. (cf. EPISOME.) (The stable, extrachromosomal (i.e., non-integrated) prophages of certain bacteriophages (e.g. BACTERIOPHAGE P1) conform to the definition of plasmid and are commonly referred to as plasmids.) Some plasmids appear to have arisen from chromosomal or mitochondrial DNA: see e.g. THREE-MICRON DNA PLASMID. The following refers primarily to prokaryotic plasmids. Plasmids occur in both Gram-positive and Gram-negative bacteria; in size they range from ca. 1.5 kb (MWt ca. 106 ) to ca. 300 kb (MWt ca. 2 ð 108 ). Most bacterial plasmids are ccc dsDNA molecules, and these are normally supercoiled (see DNA). However, some plasmids can occur as ccc ssDNA molecules [PNAS (1986) 83 2541–2545], while linear plasmids occur e.g. in Streptomyces and in Borrelia [Mol. Microbiol. (1993) 10 917–922]. Many bacterial plasmids carry one or more TRANSPOSABLE ELEMENTS. (cf. KILLER PLASMIDS; TWO-MICRON DNA PLASMIDS.) Certain obligate pathogens in the alpha subclass of Proteobacteria normally lack plasmids, although plasmids occur in other members of the same subclass. It has been suggested that species of Anaplasma, Bartonella, Brucella and Rickettsia evolved without plasmids because their relatively constant (intracellular) 593

plasmid pInv of which, RNA II, can bind at the plasmid’s origin and act as a primer, thus permitting replication. The other strand, RNA I, can interfere by base-pairing with RNA II – such that the outcome of RNA I–RNA II interaction determines the occurrence, or otherwise, of replication (for further details see COLE1 PLASMID). (It appears that RNA I is normally polyadenylated, such polyadenylation facilitating its degradation; in Escherichia coli, mutations in the pcnB gene, which encodes a poly(A)polymerase, result in RNA I molecules that are stabilized through lack of polyadenylation – the effect of which is to inhibit replication of ColE1, i.e. to reduce its copy number.) Once initiated, replication in ColE1 proceeds as in the E. coli chromosome, although in this plasmid replication occurs unidirectionally from the origin. In the R1 PLASMID (q.v.), antisense RNA molecules bind to, and inhibit translation of, the mRNA of the RepA protein – which, in turn, is involved in regulating the frequency of plasmid replication. Many of the small circular plasmids in Gram-positive bacteria (and some in Gram-negative bacteria) replicate by a ROLLING CIRCLE MECHANISM. Replication is initiated by a plasmid-encoded Rep protein which, by nicking a specific strand at the origin, generates a 30 end for synthesis. One round of replication produces a complete dsDNA plasmid and a circular ssDNA copy, the latter then being replicated to the dsDNA state from an RNA primer. In some of these plasmids initiation is controlled by regulation of the synthesis/activity of the Rep protein (as the quantity of Rep protein affects the frequency of replication); in some cases small, plasmid-encoded RNA molecules bind to the rep mRNA and bring about either premature termination of transcription or inhibition of translation. Alternatively, the Rep protein may be inactivated after only one use by binding to a small plasmid-encoded oligonucleotide. [Replication control in rolling circle plasmids: TIM (1997) 5 440–446.] In many plasmids of Gram-negative bacteria, the Rep initiator protein binds to ‘direct repeats’ of nucleotides (iterons) in the region of the plasmid’s origin of replication, thus contributing to a nucleoprotein complex that initiates replication. For example, in the F PLASMID, RepE (the E protein) carries out this function; replication proceeds by a bidirectional Cairns-type mechanism (as in the E. coli chromosome). (See also R6K PLASMID.) For each plasmid, the iterons have a characteristic number, spacing and composition. In some plasmids, Rep can also repress transcription of its own gene by binding to inverted repeat sequences overlapping the promoter; in some cases (including the F plasmid) it has been shown that, while monomers of Rep bind to iterons (promoting replication), dimers bind to the promoters of their own genes (inhibiting replication). RepA monomers (as opposed to dimers) of the Pseudomonas plasmid pPS10 may be structurally suitable for RepA–iteron binding [EMBO (1998) 17 4511–4526]. In general, plasmid replication and PARTITIONing seem likely to depend on some kind of association between the plasmid and the cytoplasmic membrane [Mol. Microbiol. (1997) 23 1–10]. Under normal growth conditions, replication is initiated at a frequency which, for a given plasmid in a given type of cell under given conditions, leads to the establishment of a characteristic COPY NUMBER. During steady-state conditions each plasmid replicates, on average, once per cell division – although the inter-replication period may vary widely from one plasmid to another. If protein synthesis is inhibited (e.g. by CHLORAMPHENICOL), some plasmids can continue to replicate, and can achieve copy numbers much higher than those achieved under normal

growth conditions. Such plasmids (e.g. ColE1) are said to be under ‘relaxed control’; a typical ‘relaxed’ plasmid is a small, non-conjugative MULTICOPY PLASMID whose copy number under normal conditions is ca. 10–30. (A ‘relaxed’ plasmid can exceed its normal copy number only under abnormal conditions. See also CLONING.) Plasmids which fail to replicate on inhibition of protein synthesis are said to be under ‘stringent control’; a typical ‘stringent’ plasmid is a large, low-copy-number CONJUGATIVE PLASMID. Whether a plasmid is ‘relaxed’ or ‘stringent’ depends on its system of replication control. Thus, e.g. in the ‘relaxed’ COLE1 PLASMID (q.v.), not only is ongoing protein synthesis not required for replication, but the inhibition of protein synthesis eliminates a protein (Rom/Rop) which is inhibitory to plasmid replication. Conversely, in ‘stringent’ plasmids replication involves e.g. the synthesis of proteins that are essential for the initiation of replication. [Control of plasmid replication: Book ref. 161, pp. 189–214.] Some plasmids have mechanisms for ensuring their persistence within a bacterial strain: see e.g. ccd mechanism in entry F PLASMID. Nomenclature. Plasmids are designated in various ways. COLICIN PLASMIDS are designated according to the colicins they encode (e.g. ColE1-K30 encodes colicin E1, ColV,I-K94 encodes colicins V and Ia). Many antibiotic-resistance plasmids are designated by the letter ‘R’ followed by a number, e.g. R1, R46 etc; others include e.g. R6K, RK2, RP1 etc. Recombinant plasmids are often indicated by the prefix ‘p’, e.g. pML31. A number of plasmids are given trivial names (e.g., 1), while the names of some indicate particular functions (see e.g. Ti plasmid under CROWN GALL, and TOL PLASMID). (See also entries for individual plasmids: e.g. COLE1 PLASMID; DELTA; F PLASMID; PBR322; PMB1; PML31; PSC101; R1 PLASMID; R46 PLASMID; R100 PLASMID; R6K PLASMID; RP1 PLASMID.) plasmid pInv See EIEC. plasmid pYV See FOOD POISONING (Yersinia). plasmin See FIBRINOLYSIN. plasminogen (profibrinolysin) An inactive precursor of FIBRINOLYSIN normally present in blood; it is a large (¾90 kDa) glycoprotein. Plasminogen has been found to bind disease-associated PRIONS, but not the normal protein (PrPC ); this property may be useful in diagnostic tests for TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES [Nature (2000) 408 479–483]. plasmodesma (pl. plasmodesmata) A fine channel in a plant cell wall or a fungal SEPTUM through which cytoplasm can pass; plasmodesmata allow continuity between the cytoplasm of adjacent cells. (See also DESMOTUBULE, PIT CONNECTION and PLANT VIRUSES.) plasmodiocarp See MYXOMYCETES. Plasmodiophora See PLASMODIOPHOROMYCETES and CLUBROOT. Plasmodiophorea See RHIZOPODA. Plasmodiophorina See GYMNOMYXA. Plasmodiophoromycetes (‘endoparasitic slime moulds’) A class of eukaryotic organisms (division MYXOMYCOTA) which are obligate intracellular parasites in plants, algae and fungi. The vegetative stage of the organisms is a plasmodium (a naked, multinucleate protoplast); hyphae and fruiting bodies are apparently never formed. Although traditionally regarded as fungi, the true taxonomic position of these organisms remains uncertain; they are apparently unrelated to other members of the Myxomycota. rRNA data studies support the idea that they may be at the base of an evolutionary line leading to the 594

Plasmodium Chytridiomycetes, Ascomycotina and Basidiomycotina, but do not exclude the possibility of a protozoal ancestry [TBMS (1983) 80 107–112]. (cf. RHIZOPODA and GYMNOMYXA.) Genera include Ligniera, Octomyxa, Plasmodiophora, Polymyxa, Sorodiscus, Sorosphaera, Spongospora, Tetramyxa, Woronina. (cf. ENDEMOSARCA; PHAGOMYXA.) Species are parasitic in e.g. higher plants (e.g. Plasmodiophora brassicae in crucifers – see CLUBROOT; Spongospora subterranea in potatoes – see POWDERY SCAB; Ligniera betae in beet; L. junci in various monocots and dicots); in algae (e.g. Woronina in Vaucheria, Sorodiscus in Chara); and in certain aquatic fungi (e.g. Woronina in Achlya, Pythium or Saprolegnia). Infected tissues often exhibit hypertrophy and sometimes hyperplasia. In e.g. Plasmodiophora brassicae and Polymyxa betae, infection of a new host is initiated when a (‘primary’) zoospore attaches to the wall of a root hair, withdraws its flagella, and encysts. Within the encysted cell there develops a tubular structure, the Rohr, containing an osmiophilic spine-like structure, the Stachel. The Rohr evaginates rapidly, and the Stachel punctures the host cell wall; the protoplast of the encysted zoospore then enters the host cell and develops into a vegetative primary (D sporangiogenous) plasmodium. When mature, this plasmodium gives rise to uninucleate ‘secondary’ zoospores, each with two smooth flagella of different lengths. [Secondary zoospore development in P. brassicae: TBMS (1984) 82 339–342.] The zoospores are released either by disintegration of the host cell or via an ‘exit tube’ arising from the zoosporangium. The role of these zoospores in the life cycle is unclear; fusion between two zoospores has been reported, but karyogamy – when it occurs – is apparently delayed. A zoospore (or fused pair of zoospores?) infects another host cell, in which it develops to form a (diploid?) secondary (D cystogenous) plasmodium. When mature, this plasmodium eventually cleaves to form a number of uninucleate, thick-walled, resistant cysts (resting spores); meiosis has been observed at this stage in several species. [Ultrastructure of meiosis in Woronina pythii : Mycol. (1984) 76 1075–1088.] In some species the cysts are arranged in characteristic clusters (cystosori). [Fine structure of the cystosorus in Spongospora subterranea: CJB (1985) 63 2278–2282.] On disintegration of the host cell the cysts are liberated into the soil where they may remain viable for long periods (e.g. years). On germination, each cyst gives rise to a biflagellate (heterokont) zoospore which can infect another host, thus initiating a new cycle. Some members of the Plasmodiophoromycetes are important as vectors of certain plant viruses: see e.g. BEET NECROTIC YELLOW VEIN VIRUS, SOIL-BORNE WHEAT MOSAIC VIRUS, POTYVIRUSES, TOBAMOVIRUSES. plasmodium A multinucleated, usually motile mass of protoplasm which is usually naked (i.e., bounded only by a plasma membrane) and which is generally variable in size and form; plasmodia are the main vegetative forms in e.g. members of the ACARPOMYXEA, MYXOMYCETES (q.v. for types), MYXOSPOREA and PLASMODIOPHOROMYCETES. (cf. PSEUDOPLASMODIUM.) Plasmodium A genus of protozoa of the suborder HAEMOSPORORINA. The genus includes the common causal agents of MALARIA in man: P. falciparum [genome: Nature (2002) 419 498–511], P. malariae (formerly P. rodhaini), P. ovale and P. vivax. P. cynomolgi and P. knowlesi are parasitic in non-human primates; they occasionally cause malaria in man, and have been widely used as models in research on human malaria. P. berghei and P. yoelii (also spelt P. yoelli ) cause rodent malaria; they have been used for testing antimalarial drugs.

The life cycle is basically similar in all species. In Plasmodium spp, sexual reproduction occurs in a mosquito and leads to the formation of large numbers of fusiform or needle-shaped uninucleate cells (sporozoites), ca. 6–18 µm in length, that are infective for the vertebrate host. (Below ca. 15° C P. falciparum will not develop within the mosquito, and below ca. 18° C its development is retarded; P. vivax can develop in mosquitoes at somewhat lower temperatures – which probably accounts for its presence in temperate as well as tropical and subtropical regions.) Transmission of the parasite occurs when the (female) mosquito takes a blood meal by inserting her proboscis into the tissues of a vertebrate host: sporozoites, present in the insect’s saliva, quickly reach the bloodstream and initiate the cycles of asexual reproduction. In man, the sporozoites rapidly enter parenchymatous cells in the liver; there, they typically grow and eventually undergo SCHIZOGONY, rupturing the liver cells and releasing into the bloodstream large numbers of minute cells (merozoites), each ca. 1 µm in diameter. This stage is called pre-erythrocytic schizogony or exoerythrocytic schizogony; its duration ranges from ca. 5 1/2 days (in P. falciparum) to ca. 15 days (in P. malariae), and is ca. 8 and 9 days respectively, in P. vivax and P. ovale. Instead of growth and schizogony, some or all of the sporozoites of some species – e.g. P. cynomolgi, P. ovale, P. vivax – form specialized cells (hypnozoites) which can remain dormant within the liver for e.g. 8–10 months; on resuming development, the hypnozoites follow the normal course of growth and schizogony and give rise to the (periodic) relapses which are characteristic of malaria caused by these species. Merozoites bind to, and enter, erythrocytes – except e.g. in P. berghei and P. yoelii, in which the merozoites parasitize reticulocytes (erythrocyte precursor cells). Within an erythrocyte a merozoite forms a central vacuole and develops into the characteristic ‘ring’ or ‘signet-ring’ stage; in stained preparations this commonly appears as a ring of cytoplasm containing a bulging nucleus. The growing cell (now called a trophozoite) obtains nutrients from e.g. the protein part of the host cell’s haemoglobin; P. falciparum apparently obtains its iron from outside the parasitized erythrocyte (see TRANSFERRIN; cf. HAEMOZOIN). At this stage the erythrocyte and/or parasite may exhibit certain inclusions: see HAEMOZOIN, MAU¨ RER’S CLEFTS, SCHUFFNER’S DOTS and ZIEMANN’S DOTS. A protein designated exp-1 was detected in a cytoplasmic compartment in P. falciparum-infected erythrocytes; it was suggested that parasite-encoded proteins pass through this compartment on their way to the erythrocyte’s plasmalemma [EMBO (1987) 6 485–491]. The fully grown parasite (now called a schizont), which no longer appears ring-shaped, subsequently undergoes schizogony to form a number of merozoites (each ca. 1 µm diam.) which are released from the ruptured erythrocyte; these merozoites can infect fresh erythrocytes. Typically, merozoites are released more or less synchronously from large numbers of parasitized erythrocytes, thus accounting for the periodic symptoms of malaria; the duration of the erythrocytic cycle (i.e., from infection to rupture) typically ranges from ca. 2 days (P. falciparum) to ca. 3 days (P. malariae), but is only 1 day in P. knowlesi. After one or more erythrocytic cycles, some of the intraerythrocytic merozoites develop into gametocytes (rather than schizonts); within the bloodstream, gametocytes may remain viable for one month or more, but they do not develop further unless ingested by an anopheline mosquito. On ingestion by a mosquito 595

plasmogamy plasmogamy Coalescence of the cytoplasm of two or more cells; in fertilization, plasmogamy is followed by KARYOGAMY. Plasmopara A genus of fungi of the PERONOSPORALES; species include P. viticola and P. halstedi, the causal agents of DOWNY MILDEWS on grape and sunflower, respectively. plasmotomy In certain multinucleate protozoa (e.g. Actinosphaera, Pelomyxa): an asexual reproductive process in which fission results in the formation of two or more multinucleate daughter cells, the nuclei of the parent cell being more or less evenly distributed between them; nuclear and cytoplasmic divisions appear to occur independently. plastics (from bacteria) See BIOPOL. plastid Any of various types of membrane-limited, typically DNA-containing organelle which occur within the cells of plants and algae but not in those of animals or prokaryotes. Examples: AMYLOPLAST, CHLOROPLAST, CHROMOPLAST, ELAIOPLAST, ETIOPLAST and LEUKOPLAST. (See also PLASTOME.) plastocyanin A copper-containing BLUE PROTEIN which acts as an electron donor to photosystem I (see PHOTOSYNTHESIS). In certain algae (e.g. Scenedesmus) plastocyanin can apparently be replaced by a c-type cytochrome in the absence of copper. [Structure and function of plastocyanin: Book ref. 146, pp. 19–31.] plastoglobuli Osmiophilic lipid globules in the stroma of a CHLOROPLAST. plastome The genetic complement of a PLASTID. plastoquinone See QUINONES and PHOTOSYNTHESIS. plate (1) A solid MEDIUM in a PETRI DISH prepared (using an ASEPTIC TECHNIQUE) by pouring a sterile molten (AGAR- or GELATIN-based) medium into a Petri dish to a depth of 3–5 mm and allowing it to set. Freshly-poured plates to be used e.g. for STREAKING should be left for 10–20 min in a 37° C hot-air incubator with the lid partly off so that the surface moisture can evaporate; such ‘drying’ before inoculation prevents unwanted spreading of the inoculum in the surface film of moisture. (See also SPREAD PLATE.) (2) A plate CULTURE. (3) (verb) To inoculate a plate: see PLATING. plate dilution test See DILUTION TEST. platelet factor 4 (PF4) See CHEMOKINES. platelets (thrombocytes) Flat, disc-like, membrane-bounded bodies (ca. 2.5 µm diam.) which occur in mammalian blood (ca. 250000/mm3 in human blood); they are formed by fragmentation of megakaryocytes in red bone marrow. Platelets adhere to rough or damaged surfaces and assist in blood clotting (though clotting can occur in their absence). Platelets contain e.g. HISTAMINE and SEROTONIN. plating (1) The act of distributing an INOCULUM on the surface of a PLATE – see e.g. SPREAD PLATE and STREAKING. (2) (serol.) The use of specifically coated plastic (or other) surfaces for the separation of specific cells (or other entities) from heterogeneous populations. The procedure is based on antigen–antibody specificity; thus, e.g., antibody, immobilized (by its Fc portion) on an inert support, will bind, and thus remove from a mixture, those cells which bear homologous cell-surface antigens. Platyamoeba See AMOEBIDA. Platymonas See TETRASELMIS. plcB gene See LISTERIOSIS. plectenchyma (mycol.) A tissue composed of hyphae or cells; such tissues occur e.g. in LICHEN thalli, in fungal fruiting bodies, etc. There are two principal types of plectenchyma: prosenchyma (prosoplectenchyma), in which the hyphae remain distinguishable, are rather loosely woven, and are more or less parallel to each other; and pseudoparenchyma (paraplectenchyma), in

the gametocytes develop into male and female gametes. In this process the (male) microgametocyte undergoes exflagellation: several nuclear divisions occur, up to eight thread-like appendages are formed, and the microgametocyte eventually breaks up to form uninucleate, uniflagellate male gametes (microgametes). A microgamete fuses with a (female) macrogamete to form a zygote which subsequently becomes motile (and is then called an ookinete or vermicule). The ookinete passes through the mosquito’s gut wall, rounds off, and forms an oocyst in the outer layer of the gut wall (adjacent to the haemocoele). Sporozoites develop within the oocyst; they are subsequently released into the haemocoele, and many find their way to the insect’s salivary glands, thus completing the cycle. Plasmodial antigens and antimalarial vacines. Certain plasmodial antigens have been used in the preparation of antimalarial vaccines. One such antigen is the circumsporozoite protein (CS protein), a protein (MWt ca. 60000) which forms a thick surface coat on the (mature) sporozoite. [CS proteins: Cell (1985) 42 401–403.] Monoclonal antibodies to CS proteins inhibit infectivity of sporozoites both in vitro and in vivo. (cf. CSP REACTION.) The CS proteins from different species of Plasmodium all contain a block of tandemly repeated peptides (though these vary in nature according to species); in e.g. P. falciparum there are multiple copies of the tetrapeptide asparagine–alanine–asparagine–proline (designated NANP), and these sequences are involved in the binding of anti-CS protein monoclonal antibodies. One experimental antimalarial vaccine consisted of a suspension of polypeptides each containing multiple repeats of NANP (and of another tetrapeptide, asparagine–valine–aspartic acid–proline (NVDP), also found in P. falciparum). Another experimental vaccine was prepared from an NANP trimer conjugated to tetanus toxoid. The ring-infected erythrocyte surface antigen (RESA) is a parasite-encoded protein found in the plasmalemma in erthrocytes infected with the ring stage of P. falciparum; it is a protein of MWt ca. 155000, and is sometimes referred to as Pf155. Antibodies to a repeated amino acid sequence in RESA inhibit the invasion of erythrocytes by merozoites in vitro. The possibility of a transmission-blocking vaccine arose from the observation that anti-gamete antibodies raised in an animal host can neutralize the gametes (of Plasmodium) in a mosquito which has taken a blood meal from that host; transmission of the parasite to a new host is therefore inhibited. The problems of developing a satisfactory antimalarial vaccine are exacerbated by ANTIGENIC VARIATION in Plasmodium. For more recent data on anti-malaria vaccines see the entry MALARIA. Subgenera of Plasmodium. Subgenera are defined on the basis of (a) the vertebrate host(s), and (b) the morphology of the erythrocytic schizont and the gametocyte. Subgenera include: Haemamoeba. Hosts: birds. Vector: the mosquito Mansonia crassipes (experimental vectors include Aedes aegypti, Anopheles spp, Culex spp). Schizonts are large, gametocytes spherical. Laverania. Hosts: primates. Vector: anopheline mosquitoes. Schizonts are large, gametocytes elongated and crescentic. Species include Plasmodium (Laverania) falciparum. Plasmodium. Hosts: primates. Vector: anopheline mosquitoes. Schizonts are large, gametocytes spherical. Species include Plasmodium (Plasmodium) cynomolgi, P. (P.) knowlesi, P. (P.) malariae, P. (P.) ovale, and P. (P.) vivax. Vinckeria. Hosts: non-primate mammals. Vector: anopheline mosquitoes. Schizonts are small, gametocytes spherical. Other (avian) subgenera: Giovannolaia, Novyella, Huffia. 596

Pluronic polyol F127 which hyphae are usually not distinguishable as such, the tissue consisting of closely packed, isodiametric or oval cells (resembling the parenchyma of higher plants). ‘Palisade plectenchyma’ occurs in the cortex of many lichen thalli, and consists of short hyphae orientated more or less perpendicular to the thallus surface. Plectonema A genus of cyanobacteria of the LPP GROUP. Although non-heterocystous, P. boryanum can carry out NITROGEN FIXATION under microaerobic (but not under aerobic) conditions. Plectrovirus (mycoplasma virus type 1 phages; L1 acholeplasmavirus group) A genus of BACTERIOPHAGES of the INOVIRIDAE. Host: Acholeplasma laidlawii ; plaques turbid (sometimes with a clear centre), 0.5–6.0 mm across. Other strains of Acholeplasma and Mycoplasma may be infected. The virions are short, naked, bullet-shaped rods (70–90 ð 14–16 nm) comprising ss cccDNA (MWt 1.5 ð 106 ) and four proteins. Proposed type member: MV-L51 (D L1 strain L51). Other member: MV-L1 (D L1 strain L1). Possible member: SV-C1 (see SPIROPLASMAVIRUSES). See also MYCOPLASMAVIRUSES. pleiotropic Refers to e.g. a gene or a mutation which has multiple effects: e.g., expression of a pleiotropic gene affects more than one phenotypic characteristic. Pleistophora See MICROSPOREA. pleomorphic Refers to e.g. an organism which exhibits PLEOMORPHISM. pleomorphism (1) In general: an inherent variability in size and shape e.g. among the cells in a pure culture of a given organism. Cells of a pleomorphic organism (e.g. Corynebacterium spp, Propionibacterium spp) may occur in a wide range of indeterminate forms which are often variations of a single basic shape: e.g. the cells may be basically rod-shaped but may be swollen at one or both ends, curved or straight, branched or unbranched, etc. (cf. POLYMORPHISM sense 1.) (2) Syn. POLYMORPHISM sense 1. (3) (mycol.) Degenerative changes – e.g. loss of the ability to form conidia and/or to synthesize pigment – which occur in some fungi (e.g. certain dermatophytes) when propagated in laboratory cultures. Pleospora See DOTHIDEALES. Plesiomonas (‘C27 organisms’) A genus of Gram-negative bacteria of the VIBRIONACEAE. Cells: straight, round-ended rods, 0.8–1.0 ð 1–3 µm. Usually motile with 2–5 lophotrichous unsheathed flagella; lateral flagella may be formed in young cultures on solid media. Optimum growth temperature: ca. 35–38° C. Growth does not require NaCl and cannot occur with 7.5% NaCl. Growth media: e.g. SS, XLD or Hektoen agars [media, identification etc: Book ref. 46, pp. 1285–1288]. Oxidase Cve; acid but not gas is formed from glucose and e.g. inositol; extracellular DNase, gelatinase and lipase are not formed; most strains are sensitive to O/129. Strains may possess the enterobacterial common antigen, and a few share an O antigen with Shigella sonnei. GC%: 51. Type species: P. shigelloides – found in association with fish and other aquatic animals and in mammals; strains can cause e.g. gastroenteritis in man. [Book ref. 22, pp. 548–550.] According to 5S rRNA sequence analysis, P. shigelloides is more closely related to Proteus mirabilis than is Proteus vulgaris and should therefore be included in the genus PROTEUS as Proteus shigelloides [SAAM (1985) 6 171–182]. (See also ENTEROBACTERIAL COMMON ANTIGEN.) Pleurasiga See CHOANOFLAGELLIDA. Pleurastrophyceae See TETRASELMIS and TREBOUXIA.

A genus of filamentous green algae related to the filaments are branched and lack holdfasts. P. terrestre may also grow as unicells under certain conditions. Pleuroascus See EUROTIALES. Pleurocapsa See PLEUROCAPSA GROUP. Pleurocapsa group A large and diverse group of unicellular CYANOBACTERIA (section II) in which growth and binary fission lead to the formation of irregular, sometimes pseudofilamentous cell aggregates; baeocytes initially lack a fibrous outer cell wall layer and are motile (by gliding). In some members (subgroup I) growth of the baeocyte is symmetrical, resulting in a spherical vegetative cell, while in others (subgroup II) growth is asymmetrical and vegetative cells are elongated prior to the onset of binary fission. The group includes organisms previously included in many phycological genera (e.g. Hyella, Pleurocapsa) which were based on characters such as endolithic habit, arrangement of vegetative cells in aggregates, etc. GC%: 39–47. pleurocapsalean (1) Refers to BAEOCYTE-forming CYANOBACTERIA (section II). (2) Refers to any member of the phycological order Pleurocapsales. Pleurocapsales See CYANOBACTERIA. Pleurococcus A genus of unicellular green algae (division CHLOROPHYTA) which are extremely common on wood, bark etc; the cells generally occur in characteristic packets. The organisms have been referred to by various names (Pleurococcus viridis, P. vulgaris, Protococcus viridis, etc), but apparently should be called Desmococcus olivaceus [Taxon (1985) 34 671–672]. pleurodynia See BORNHOLM DISEASE. Pleuronema See SCUTICOCILIATIDA. Pleurosigma See DIATOMS. Pleurotus A genus of fungi of the APHYLLOPHORALES (family Polyporaceae) in which the basidiocarp is commonly pileate and stipitate (stipe often eccentric or lateral); the hymenium is borne on decurrent lamellae (see LAMELLA). P. ostreatus is an edible species (see OYSTER FUNGUS) which grows on wood and which can be pathogenic for certain trees, particularly beech (Fagus). plicate Folded. Plodia interpunctella GV See GRANULOSIS VIRUSES. ploidy The number of (complete) sets of chromosomes (or AUTOSOMES) in a cell. (See also DIPLOID, HAPLOID, POLYPLOID, ANEUPLOID.) plugging (of pipettes) The insertion of a small plug of COTTON WOOL into the wide end of a pipette or PASTEUR PIPETTE before sterilization; liquids being pipetted are thus protected from contamination from the rubber bulb, pi-pump etc. plum pox (sharka disease) A disease affecting many species of Prunus (e.g. plum, apricot, peach, blackthorn); it is caused by a virus of the POTYVIRUSES and is transmitted by aphids and by infected rootstocks. Symptoms commonly include diffuse mottling or ring-spots on the leaves, premature fruit-drop, and (depending on fruit type) dark bands or rings, or grooving and pitting, on the fruits. plumbagin 5-Hydroxy-2-methyl-1,4-naphthoquinone. plunging jet See JET LOOP FERMENTER. pluracidomycins CARBAPENEM antibiotics. plurivorous Able to use a range of hosts or substrates. Pluronic polyol F127 A copolymer of ethylene oxide and polypropylene oxide used e.g. as a solidifying agent for culture media. (See also MEDIUM.) A polyol-solidified medium can be liquefied by cooling, the gel–liquid transition temperature depending on the concentration of polyol used. The clear, paste-like medium is apparently unsuitable for streaking, but is Pleurastrum

TREBOUXIA;

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plus-progamone reported to be suitable for use e.g. in the pour plate technique for heat-sensitive organisms, and in gradient gel systems. [JGM (1984) 130 731–733.] plus-progamone See PHEROMONE. plus strand (of a gene) (mol. biol.) See CODING STRAND. plus strand (virol.) See VIRUS. Pluteaceae See AGARICALES. PM2 phage group Syn. CORTICOVIRIDAE. pMB1 A small, multicopy PLASMID which carries genes for colicin E1, the colicin E1 immunity protein, and the EcoRI restriction and modification enzymes. pMB1 belongs to the same incompatibility group as the COLE1 PLASMID, and its ori region shares extensive homology with that of the ColE1 plasmid. pmf Proton motive force: see CHEMIOSMOSIS. pMG25 See INCOMPATIBILITY. PML PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY. pML31 An autonomous 9-kb plasmid obtained by digestion of the F PLASMID with EcoRI restriction endonuclease and the ligation of a part of the plasmid (containing an origin of replication) with an antibiotic-resistance determinant. (See also MINI-F PLASMID.) PMN Polymorphonuclear leucocyte (‘polymorph’; granulocyte): a type of LEUCOCYTE which has a lobed nucleus and granular cytoplasm (hence ‘granulocyte’); diam. ca. 10–15 µm. PMNs include NEUTROPHILS, BASOPHILS and EOSINOPHILS – so named because of the affinity of their cytoplasmic granules for particular dyes; they are short-lived cells which do not replicate and which are continually replaced by cells derived from bone marrow. ‘Polymorph’ may refer to PMNs in general, but is sometimes used to refer solely to neutrophils. PNA (peptide nucleic acid) An analogue of DNA, the backbone chains of which are modified polypeptides (rather than sugar–phosphate units). Two strands of PNA can hybridize to form a DNA-like helical duplex [Nature (1994) 368 561–563]; the existence of such a molecule has prompted the suggestion that pre-biotic nucleic acids may not necessarily have had a sugar–phosphate backbone. A strand of PNA can hybridize with a strand of DNA; this may be of use in DNA CHIP technology. PNA probes have been used for identifying and enumerating specific microorganisms by an in situ hybridization technique [JAM (2001) 90 180–189]. pncA gene See PYRAZINAMIDE. pneumatocyst (air bladder/vesicle; bladder; gas bladder) A gasfilled structure normally present in the thallus of certain algae (e.g. species of Fucus, Pelagophycus and Sargassum); a given thallus may contain many pneumatocysts. Pneumatocysts, which are generally observable as distinct swellings, contribute buoyancy to the thallus. (cf. GAS VESICLE.) pneumococcal pneumonia See PNEUMONIA (a). pneumococcus Streptococcus pneumoniae. pneumococcus capsule swelling reaction Syn. QUELLUNG PHENOMENON. Pneumocystis A genus of fungi (formerly regarded as protozoa) now classified as members of the subdivision Ascomycotina. P. carinii is an important causal agent of pneumonia in HIVinfected patients; however, it can also give rise to infection in e.g. children and elderly individuals in the absence of HIV infection [BCID (1995) 2 461–470]. P. carinii is also a causal agent of disease in animals (e.g. pigs). The cells of P. carinii are ¾1–5 µm; asci (10–12 µm) each contain up to eight ascospores. No satisfactory culture technique has been developed.

Diagnosis of Pneumocystis pneumonia typically involves microscopy of induced sputum or of fluid from broncho-alveolar lavage. Asci can be seen by staining with either TOLUIDINE BLUE or Gomori’s silver stain. Individual cells are detected with Giemsa or Wright’s stain [AJCP (1984) 81 511–514]. Immunofluorescence stains are also available for P. carinii. [Pneumocystis carinii (epidemiology, pneumonia, laboratory diagnosis, therapy etc.): BCID (1995) 2 409–576. Immune response to P. carinii infection: TIM (1998) 6 71–75. P. carinii pneumonia in pigs (immunohistochemical study): VR (2000) 147 544–549.] pneumolysin See THIOL-ACTIVATED CYTOLYSINS. pneumonia Inflammation of the lungs. It may involve the alveoli (cf. ALVEOLITIS) and/or the interstitial tissues (interstitial pneumonia); inflammation may affect most of the parenchyma in one or more lobes (lobar pneumonia) or may be diffuse. Pneumonia is commonly due to bacterial infection, often secondary to e.g. viral URTI (such as INFLUENZA) or other infection (e.g. MEASLES); other causal agents include e.g. viruses (see also PNEUMOCYSTIS). The pathogen may gain access to the lungs by inhalation or via the blood or lymph systems (see e.g. bubonic PLAGUE). Conditions which predispose to pneumonia include chronic lung disease, debilitating illness, immunosuppression, etc. Symptoms of pneumonia generally include fever, chills, rigors, malaise, dyspnoea and chest pain; cough may be initially dry, later productive of purulent, sometimes bloody sputum. Lab. diagnosis: examination of sputum, pleural fluid etc by microscopy, culture, and/or serological techniques (e.g. CIE). Sputum may be obtained by percutaneous aspiration from the trachea, rather than by expectoration, to reduce contamination by members of the normal respiratory tract flora. (a) Pneumococcal pneumonia (‘classical lobar pneumonia’), caused by certain strains of Streptococcus pneumoniae (the ‘pneumococcus’), is the commonest form of bacterial pneumonia. Infection may be primary or secondary. The pathogen, present e.g. in the upper respiratory tract of carriers, gains access to the lungs by inhalation. Incubation period: 1–3 days. Affected lobes typically become consolidated, i.e., solidifed with inflammatory material (leucocytes, fibrin, pneumococci etc). Sputum is initially purulent, becoming ‘rusty’ or blood-stained as the consolidation breaks down. Complications include e.g. pericarditis, meningitis etc. Chemotherapy: e.g penicillins, erythromycin. Polyvalent vaccines containing polysaccharide antigens of various common pneumococcal serotypes are available for certain high-risk patients [NEJM (1984) 310 651–653; AIM (1986) 104 106–109, 110–112, 118–120]. (b) Haemophilus influenzae (usually type b) may cause primary pneumonia (mainly in children) or secondary pneumonia in patients with e.g. viral respiratory tract infection. The pneumonia may be diffuse or lobar, and abscesses may develop. Chemotherapy: e.g. ampicillin; tetracycline; chloramphenicol. (c) Staphylococcus aureus can cause lobar or diffuse interstitial pneumonia, usually following e.g. influenza or staphylococcal septicaemia. Abscesses may develop in lungs and/or pleura. Sputum is yellow, purulent, and sometimes bloody. Proteases from some strains of S. aureus may activate influenza virus virions (by cleaving their haemagglutinins: see INFLUENZAVIRUS), thus promoting combined viral–bacterial pneumonia [Nature (1987) 325 536–537]. Chemotherapy: e.g. b-lactamaseresistant b-lactam antibiotics. (d) Friedl¨ander’s pneumonia (caused by Klebsiella pneumoniae) is a severe form which usually occurs as a complication of e.g. chronic lung disease. Typically, one or more lobes become 598

poky mutant densely infiltrated, and thin-walled abscesses occur. Sputum is often viscid, gelatinous and blood-stained. Chemotherapy: e.g. gentamicin; amikacin; cephalosporins. (e) Streptococcus pyogenes may cause primary or secondary pneumonia which is usually diffuse and often leads to empyema. Chemotherapy: e.g. penicillins. (f) Various other Gram-negative bacteria may cause primary or secondary pneumonia – particularly in the very young or elderly, debilitated, or immunosuppressed, often following antibiotic therapy. Nosocomial pneumonia may be due e.g. to species of Enterobacter, Klebsiella, Proteus, Serratia, Escherichia coli or Pseudomonas aeruginosa. Anaerobes (e.g. Bacteroides spp) may infect the lungs, often with abscess formation; infection originates from the mouth or – via the lymph or blood systems – from e.g. intra-abdominal abscesses. (See also LEGIONELLOSIS.) (g) Certain viruses (e.g. adenoviruses, coxsackieviruses, parainfluenza viruses, respiratory syncytial virus) can cause pneumonia, particularly in small children. (See also (c), above.) Cf. PNEUMONITIS and PRIMARY ATYPICAL PNEUMONIA. See also e.g. ASPERGILLOSIS; COCCIDIOIDOMYCOSIS; HISTOPLASMOSIS; PLAGUE; PNEUMOCYSTIS. For pneumonia in animals see e.g. ATYPICAL INTERSTITIAL PNEUMONIA; BOVINE RESPIRATORY DISEASE; CALF PNEUMONIA; CONTAGIOUS BOVINE PLEUROPNEUMONIA: JAAGSIEKTE; MAEDI. pneumonia of mice virus See PNEUMOVIRUS. pneumonic pasteurellosis See BOVINE RESPIRATORY DISEASE. pneumonitis (1) Syn. PNEUMONIA. (2) Inflammation of the lungs as part of a more generalized syndrome, or resulting from chemical or physical injury or allergy (as opposed to infection). (cf. ALVEOLITIS.) pneumotropic Having an affinity for the lungs. Pneumovirus A genus of viruses of the PARAMYXOVIRIDAE in which the virions have neither haemagglutinin nor neuraminidase activity. Type species: (human) respiratory syncytial virus (RSV), an important cause of respiratory disease in humans (particularly infants and young children) – see e.g. BRONCHIOLITIS, COMMON COLD, CROUP, PNEUMONIA (g). [Review of RSV: Arch. Virol. (1985) 84 1–52. Experimental models for RSV infections: RMM (1996) 7 115–122.] Other members of the genus: bovine respiratory syncytial virus (see BOVINE RESPIRATORY DISEASE) and pneumonia of mice virus (common in laboratory mice, in which infection is latent or mild). PNPase POLYNUCLEOTIDE PHOSPHORYLASE. P/O ratio (P:O ratio) A measure of the efficiency of OXIDATIVE PHOSPHORYLATION: the number of molecules of ATP formed per atom of oxygen used. (cf. HC /O RATIO.) POC Particulate organic carbon. (cf. DOC.) Pocheina See ACRASIOMYCETES. pock (1) (med.) A cutaneous pustule, as formed e.g. in SMALLPOX. (2) (virol.) A lesion produced on the CAM (see EMBRYONATED EGG) by certain viruses; the nature and number of pocks formed can be useful in the identification and assay of the virus (see e.g. COWPOX VIRUS, VACCINIA VIRUS and VARIOLA VIRUS). pocket rot (of timber) A form of WHITE ROT in which decay is limited to small, discrete regions (‘pockets’) and LIGNIN is attacked preferentially. Pocket rot fungi include Phellinus pini (in conifers) and Inonotus sp (in oaks). [Mycol. (1983) 75 552–556.] pod rot (frosty pod; Quevedo disease) A CACAO DISEASE caused by Moniliophthora roreri and characterized by a whitish (‘frosted’) powdery covering of spores on the pods; the spores

subsequently darken. [Phytopathol. Paper number 24 (March, 1981).] Podaxales See GASTEROMYCETES. podetium (lichenol.) A vertical, stem-like, lichenized structure of generative tissue (sometimes called a ‘secondary thallus’) which develops from a crustose, squamulose or foliose basal (‘primary’) thallus and which supports one or more hymenial discs (‘apothecia’); the entire podetium – together with its hymenial disc(s) – should be regarded as a fruticose APOTHECIUM [Lichenol. (1982) 14 105 – 113]. (cf. PSEUDOPODETIUM.) Podetia are formed e.g. by most species of CLADONIA; they are usually hollow and may be branched or unbranched or – in some Cladonia spp – may terminate in a cup- or funnel-shaped structure (the ‘scyphus’). (According to the above definition, structures resembling podetia but lacking algae are not true podetia; such structures are formed e.g. by Baeomyces spp and Cladonia caespiticia.) Podophrya See SUCTORIA. podophyllotoxin A substance of plant origin (obtained from Podophyllum peltatum) which has antitumour activity. Podophyllotoxin, which contains a trimethoxy-substituted aromatic ring, binds to TUBULIN at a site close to (or identical with) that at which COLCHICINE binds – inhibiting the assembly of MICROTUBULES. Some epipodophyllotoxins (which have been used as antitumour agents) appear to affect DNA synthesis (rather than microtubule assembly) – apparently by inhibiting topoisomerase activity. Podoscypha See APHYLLOPHORALES (Stereaceae). Podosphaera See ERYSIPHALES. Podospora A genus of fungi (order SORDARIALES) which occur e.g. on soil and dung; the organisms form dark ascospores, each bearing gelatinous appendages, in persistent asci formed in perithecia. In P. anserina the four binucleate ascospores per ascus each contain nuclei of compatible mating types (cf. secondary HOMOTHALLISM). (See also AMIXIS.) Podoviridae A family of DNA-containing BACTERIOPHAGES which have isometric or elongated heads and short (ca. 20 nm) non-contractile tails. Members include BACTERIOPHAGE N4, P22, f29, T3, T7 (type species), and TBILISI PHAGE (see separate entries). (See also MV-L3 PHAGE GROUP and SPIROPLASMAVIRUSES (SV-C3).) Pogosta disease See SINDBIS VIRUS. Poikilovirus See ALPHAHERPESVIRINAE. point mutation (1) A type of MUTATION in which a single nucleotide is replaced by another: see TRANSITION MUTATION and TRANSVERSION MUTATION. A point mutation in a structural gene may result in a MIS-SENSE MUTATION, a NONSENSE MUTATION, or a SAME-SENSE MUTATION. Mutagens which can induce point mutations include e.g. 5-BROMOURACIL, HYDROXYLAMINE and NITROUS ACID. (2) Any mutation involving a single nucleotide, including the gain or loss of a nucleotide (resulting in a FRAMESHIFT MUTATION) as well as transition and transversion mutations. (cf. MULTISITE MUTATION.) poising system See REDOX POTENTIAL. Poitrasia See MUCORALES. pokeweed mitogen (PWM) Any of five mitogenic LECTINS (designated Pa-1 to Pa-5) obtained from the roots, leaves and berries of the pokeweed, Phytolacca americana. All can stimulate T cells; Pa-1, in the presence of T cells and macrophages, can stimulate Ig secretion by B cells. PWM binds to oligomers of b-D-acetylglucosamine. poky mutant A mutant strain of Neurospora which has a subnormal rate of growth owing to a deficiency in its respiratory 599

pol genes polaroplast See MICROSPORA. polB gene See DNA POLYMERASE. polC gene See DNA POLYMERASE. poliomyelitis (polio; infantile paralysis) An acute infectious disease of humans, particularly children, caused by any of three serotypes of human poliovirus (see ENTEROVIRUS). (A few nonhuman primates, e.g. chimpanzees, are also susceptible.) Transmission occurs by the faecal–oral route (e.g. by person-toperson contact or via sewage-contaminated water). Incubation period: 3–35 (usually 7–14) days. Infection may be asymptomatic; clinical forms are usually mild and self-limiting, with fever, headache, nausea and vomiting, and pharyngitis (abortive poliomyelitis). In a minority of cases the virus may invade the CNS, causing inflammation and destruction of the lower motor neurones in the brain stem and spinal cord. In non-paralytic poliomyelitis symptoms include those of MENINGITIS (e.g. stiffness of the neck and back). In paralytic poliomyelitis there is weakness and eventually flaccid paralysis of muscles (commonly of the legs); the paralysis may or may not be permanent. Polio is not usually fatal, but may be if respiratory muscles become involved. Lab. diagnosis: serological tests; culture of the virus from pharyngeal secretions and faeces. (See also SALK VACCINE and SABIN VACCINE.) polioviruses See ENTEROVIRUS. Polish infectious dropsy (of carp) See CARP ERYTHRODERMATITIS. pollen mould Bettsia alvei (q.v.). pollution (environmental) See ENVIRONMENTAL POLLUTION. poly(A) tail See MRNA. polyacetylenes (polyynes) Linear compounds, containing both double and triple bonds, which are produced by certain higher fungi (particularly basidiomycetes) and which, in some cases, exhibit antifungal and antibacterial activity; the polyacetylene molecule usually has an oxygen-containing terminal group (e.g. a carboxyl or hydroxyl group). For example, mycorrhizal Leucopaxillus cerealis produces diatretyne nitrile (HOOC
CHDCH
CC
CC
CN) which is active e.g. against Phytophthora cinnamomi. polyacrylamide gel electrophoresis ELECTROPHORESIS using a polyacrylamide gel – see e.g. SDS-PAGE. polyadenylated mRNA See MRNA. polyamines Polycationic compounds containing two or more amino groups; they appear to occur in all animal, plant and microbial cells and in certain viruses. Putrescine [NH2 (CH2 )4 NH2 ], spermidine [NH2 (CH2 )3 NH (CH2 )4 NH2 ] and spermine [NH2 (CH2 )3 NH(CH2 )4 NH(CH2 )3 NH2 ] appear to be almost universally present in prokaryotic and eukaryotic microorganisms. However, their cellular location(s) and biological function(s) are still not known, although numerous effects on e.g. nucleic acid structure and enzyme activity have been observed in vitro; polyamines may have a role e.g. in protein synthesis in bacteria, and are necessary for the replication of at least some bacteriophages, including the T-even phages (which contain putrescine and spermidine) and bacteriophage l. (See also BACTERIOPHAGE fW-14.) Polyamines are synthesized primarily from amino acids – e.g. putrescine may be formed by the decarboxylation of ornithine or by the combined action of arginine decarboxylase and agmatine ureohydrolase. (See also DECARBOXYLASE TESTS.) In bacteria the polyamine content is significantly affected by the growth conditions. A number of novel polyamines have been described from extreme thermophiles: e.g. ‘Thermus thermophilus’ contains polyamines such as thermine

chain. The mutant gene (D mi-1 or maternal inheritance-1 gene) appears to occur in the mitochondrial DNA, and is transmitted to sexually-derived progeny only from a female (ascogonial) parent; such MATERNAL INHERITANCE is presumed to be due to the absence of mitochondria in the (male) microconidium. (cf. PETITE MUTANT.) pol genes (1) See DNA POLYMERASE. (2) See RETROVIRIDAE. polA gene See DNA POLYMERASE. polar body An intracellular granule at one or each pole of a cell – e.g. the deposits of PHB in Beijerinckia. polar cap See MICROSPORA. polar capsule See MYXOZOA. polar fibre See MITOSIS. polar filament See MICROSPORA and MYXOZOA. polar membrane A multilaminar intracellular membrane, attached to the inside of the cytoplasmic membrane by barlike links, present at the poles (sites of flagellar attachment) of the cells in species of helical and vibrioid bacteria (e.g. Aquaspirillum, Campylobacter, Ectothiorhodospira, Oceanospirillum, Rhodospirillum, Spirillum). polar microtubule See MITOSIS. polar mutation A mutation which, in addition to affecting the gene in which it occurs, reduces the expression of any gene(s) in the same (polycistronic) operon on the promoter-distal side of the mutation – a phenomenon known as polarity; genes between the promoter and the mutation are not affected. Thus, e.g., in the LAC OPERON a nonsense mutation in the y gene may eliminate permease synthesis, does not affect b-galactosidase synthesis, and reduces the amount of transacetylase synthesis. The mutation is said to be strongly polar when the expression of promoterdistal genes is strongly inhibited; weakly polar mutations cause only slight inhibition. The strength of polarity depends on the distance between the mutation and the end of the gene in which it occurs (i.e., between the mutation and the next translation initiation site), being greatest when this distance is greatest. According to one model for polarity, cessation of translation (due e.g. to the presence of a nonsense mutation) may expose in the mRNA a r-dependent TRANSCRIPTION termination site which is normally protected from the r factor by the presence of ribosomes; interaction of r with this site results in premature termination of transcription and hence loss of expression of promoter-distal genes. Polar mutations can be suppressed by mutations in the rho gene, the mutant r factor apparently failing to interact with the premature termination signal; polarity suppressors thus restore expression of genes downstream of the mutant gene but not of the mutant gene itself. (cf. SUPPRESSOR MUTATION.) The polar effects of certain TRANSPOSABLE ELEMENTS (e.g. IS2 ) have been attributed to the presence of a r-dependent terminator within the TE sequence. In some cases a polar mutation does not appear to affect transcription; in such cases ribosomes, having dissociated from the mRNA at a nonsense mutation, may be unable to re-initiate translation at the next initiation site – possibly because of the formation of a secondary structure in the untranslated mRNA. polar plaque Syn. SPINDLE POLE BODY. polar ring An osmiophilic annular structure, one or more of which occur at the anterior end in members of the APICOMPLEXA. Polar ring(s) may act as support(s) for the opening in the inner layer of the pellicle, and they may be involved in the function of the conoid. polarilocular Refers to a lichen spore consisting of two cells which are separated by a thick septum that has a central canal. (See also TELOSCHISTALES.) 600

poly-b-hydroxybutyrate and small molecules; the polyene molecule may form a pore in the membrane through which such leakage may occur. These antibiotics are microbistatic at low concentrations, microbicidal at higher concentrations. Macrolide polyenes are effective against yeasts and other fungi and also against protozoa, but not against most bacteria (whose membranes lack sterols – cf. MYCOPLASMA). The selective toxicity of the clinically useful macrolide polyenes is apparently due, at least in part, to their greater affinity for ergosterol (a principal sterol in fungal cytoplasmic membranes) compared with cholesterol (the main sterol in mammalian cell membranes) (cf. FILIPIN). Macrolide polyenes include e.g. AMPHOTERICIN B; AUREOFUNGIN; CANDICIDIN B; ETRUSCOMYCIN; FILIPIN; HAMYCIN; NYSTATIN; PERIMYCIN; PIMARICIN; and TRICHOMYCIN. (b) A group of structurally novel polyenes (produced by actinomycetes [FEMS (1984) 25 121–124]) which are active against prokaryotes, inhibiting PROTEIN SYNTHESIS. In bacteria, aurodox, azdimycin, dihydromocimycin, efrotomycin, factumycin, kirromycin (D mocimycin) and kirrothricin all act by binding to EF-Tu and preventing its dissociation from the ribosome; the structurally related antibiotic pulvomycin binds EFTu-GTP and prevents the formation of the aa-tRNA-GTP-EF-Tu complex, thus preventing the binding of aa-tRNA to the ribosomal A site. In archaeans, elongation factors are generally insensitive to kirromycin, and the elongation factors of only some archaeans are sensitive to pulvomycin [JB (1986) 167 265–271]. polyether antibiotics See MACROTETRALIDES. polyethylene glycol (PEG; Carbowax) A polymer, H(OCH2 . CH2 )n OH, available in a range of grades of mean MWt between ca. 200 and ca. 20000; above MWt ca. 1000 it is a solid, below it is a liquid. PEG is used e.g. in cell fusion (see e.g. HYBRIDOMA), in PROTOPLAST FUSION, in artificial TRANSFORMATION systems, and as a precipitating agent in clinical chemistry. PEG is also used for concentrating, by osmosis, serum and other aqueous solutions and suspensions; serum etc is placed in a U-shaped tube of semipermeable material (e.g. Visking tubing) and the tubing partly submerged in a concentrated aqueous solution of PEG. poly(ethylene oxide) A high-MWt polymer (
CH2 CH2 O
)n used e.g. to increase the viscosity of a medium in order to slow down rapidly motile organisms – see COUNTING METHODS. (cf. FICOLL.) polygenic mRNA See MRNA. polyhedra (virol.) Large inclusion bodies formed in the cells of insects infected with certain viruses (see CYTOPLASMIC POLYHEDROSIS VIRUS GROUP and BACULOVIRIDAE); a polyhedron is composed of a matrix of crystalline, virus-specific protein (polyhedrin) in which mature virions are embedded (‘occluded’). Polyhedra are stable structures which appear to give some protection to the virions they contain; they serve as vehicles for virus transmission: ingestion of polyhedra by a new host is followed by degradation of polyhedrin in the gut and the release of infectious virions. Polyhedra can be isolated from infected cells e.g. by differential centrifugation. polyhedral bodies See CARBOXYSOMES. polyhedrin See POLYHEDRA and BACULOVIRIDAE. polyhedrosis An INSECT DISEASE caused by a NUCLEAR POLYHEDROSIS VIRUS or by a virus of the CYTOPLASMIC POLYHEDROSIS VIRUS GROUP. poly-b-hydroxyalkanoate See POLY-b-HYDROXYBUTYRATE. poly-b-hydroxybutyrate (PHB) A linear polymer of b-hydroxybutyrate (D(
)-3-hydroxybutyrate): H-[O.CH(CH3 ).CH2 .CO]n OH. It occurs as refractile granules in the cells of various

[D sym-norspermine: NH2 (CH2 )3 NH(CH2 )3 NH(CH2 )3 NH2 ], sym-homospermidine [NH2 (CH2 )4 NH(CH2 )4 NH2 ], thermospermine [NH2 (CH2 )3 NH(CH2 )3 NH(CH2 )4 NH2 ] and also caldopentamine [NH2 (CH2 )3 NH(CH2 )3 NH(CH2 )3 NH(CH2 )3 NH2 ]. These substances have been implicated in the maintenance of thermostability in cell components, enzymes, etc; however, symhomospermidine has also been found in mesophilic bacteria [FEMS (1983) 20 159–161]. [Reviews: MR (1985) 49 81–99; ARB (1984) 53 749–790.] Polyangium See MYXOBACTERALES. poly(A)polymerase See MRNA. polybetahydroxybutyrate See POLY-b-HYDROXYBUTYRATE. polycentric Refers to a thallus in which a number of regions, in different parts of the thallus, each have a reproductive function. (cf. MONOCENTRIC.) polychlorinated biphenyls (PCBs) See BIOREMEDIATION. polychrome methylene blue See METHYLENE BLUE. polycistronic mRNA See MRNA. polyclonal activator (immunol.) Any non-specific activator of lymphocytes, i.e. any agent which can bring about differentiation/proliferation in each of a number of different clones. Polyclonal activators for B LYMPHOCYTES include lipopolysaccharides and various mitogens; such agents are THYMUSINDEPENDENT ANTIGENS. SUPERANTIGENS are polyclonal activators for T LYMPHOCYTES. polyclonal antiserum Any antiserum prepared by injecting an animal with a given antigen; it contains a heterogeneous population of antibodies – each antibody being specific to one of the (usually many) determinants present on the antigen. (cf. MONOCLONAL ANTIBODIES.) polycycline See TETRACYCLINES. Polycystinea See RADIOLARIA. Polydnaviridae A family of viruses [Intervirol. (1986) 25 141–143], previously classified as subgroup D of the BACULOVIRIDAE, characterized by their polydisperse ccc dsDNA genomes. Virus replication occurs in host cell nuclei; virions are not occluded. The viruses infect certain species of parasitic hymenopteran insects. Two distinct groups (genera) are recognized. In one group (genus unnamed) the virion has a cylindrical nucleocapsid of variable length, and virions are surrounded – either individually or in groups – by a unit membrane envelope; these viruses infect braconid wasps. In the other group (genus Polydnavirus) the virions have fusiform nucleocapsids surrounded by two envelopes; these viruses infect ichneumonid wasps (e.g. Hyposoter spp). Viruses of both groups can apparently be transmitted vertically [Virol. (1986) 155 120–131]. Type species: polydnavirus type 1 (Hyposoter exiguae virus). polyene antibiotics ANTIBIOTICS which contain region(s) of conjugated double bonds. There are two structurally and functionally distinct types. (a) A group of MACROLIDE ANTIBIOTICS (produced by streptomycetes) characterized by a large lactone ring containing a rigid, lipophilic region of (generally) unsubstituted, all-trans conjugated double bonds and a flexible, hydrophilic, hydroxylated region; the lactone may be substituted with aminosugar, carboxyl, aliphatic or aromatic groups. These polyenes are classified according to the number of conjugated double bonds they contain (e.g. tetraenes, heptaenes). They are poorly soluble in water but are soluble in organic solvents; they are unstable in solution in the presence of light owing to photo-oxidation of the double bonds. The macrolide polyenes interact with sterols in the cytoplasmic membrane of sensitive organisms, causing leakage of ions 601

Polyhymenophorea PROKARYOTES,

including cyanobacteria and members of the Chromatiaceae and Rhodospirillaceae. PHB synthase (and possibly also de-polymerizing enzymes) occur at the surface of the granules. Each mature granule is bounded by a layer apparently ca. 0.002% w/v, potassium permanganate imparts a pink coloration to water; this, together with the toxicity of its manganese component, makes potassium permanganate unsuitable for the disinfection of potable water. potassium pump See ION TRANSPORT. potassium transport See ION TRANSPORT. potato aucuba mosaic virus See POTEXVIRUSES. potato black ringspot virus See NEPOVIRUSES. potato blight See EARLY BLIGHT and LATE BLIGHT. potato diseases See e.g. BLACKLEG (2); EARLY BLIGHT; GANGRENE (2); LATE BLIGHT; POTATO SCAB; POTATO VIRUS Y; POWDERY SCAB; SILVER SCURF; SPRAING; WART DISEASE. potato leaf roll virus See LUTEOVIRUSES. potato mop top virus See SOIL-BORNE WHEAT MOSAIC VIRUS, SPRAING and TOBAMOVIRUSES. potato paracrinkle virus See CARLAVIRUSES. potato scab (common scab) A POTATO DISEASE caused by Streptomyces scabies. The disease occurs particularly in light, sandy, alkaline soils; corky scabs of various sizes typically develop on the surface of tubers, deeper lesions sometimes occurring. In heavy, wet soils POWDERY SCAB may develop. potato slope A wedge-shaped piece of potato autoclaved (in a test-tube or bottle) and used as a MEDIUM. potato spindle tuber viroid See VIROID. potato virus A See POTYVIRUSES. potato virus M See CARLAVIRUSES. potato virus S See CARLAVIRUSES. potato virus T A filamentous (about 640 ð 12 nm), ssRNAcontaining virus (possible member of the CLOSTEROVIRUSES) which has a rather limited host range; in potato plants, infection may be symptomless (latent) or may result in a mild leaf mottle. Transmission occurs via seeds in some solanaceous plants. potato virus X See POTEXVIRUSES. potato virus Y (PVY) The type member of the POTYVIRUSES. Virion: ca. 730 ð 11 nm. PVY infects mainly plants of the Solanaceae, causing important diseases in several commercial crop plants (e.g. potato, capsicum, tobacco, tomato). In the potato, symptoms depend on virus strain, host cultivar, and environmental conditions. PVY YN strains may cause necrotic rings or spots, with mild mottling appearing later in the growing season; symptoms appearing in the second and subsequent years may include mild to severe mottling. PVY YO strains may cause necrosis, mottling or yellowing of leaflets, leaf-drop, and

606

Powassan encephalitis mosaic virus, carnation vein mottle virus, carrot thin leaf virus, celery mosaic virus, cocksfoot streak virus, cowpea aphid-borne mosaic virus (of which Azuki bean mosaic virus is a strain), leek yellow stripe virus, lettuce mosaic virus, onion yellow dwarf virus, Papaya ringspot virus, parsnip mosaic virus, peanut mottle virus, PLUM POX virus, potato virus A, soybean mosaic virus, sugarcane mosaic virus (of which maize dwarf mosaic virus is a strain), tobacco etch virus, tulip breaking virus, turnip mosaic virus. Many other viruses have been tentatively included as ‘possible members’ of the potyviruses. These include (a) certain aphidborne viruses: e.g. carrot mosaic virus, celery yellow mosaic virus, groundnut eyespot virus, tobacco vein mottling virus, tomato (Peru) mosaic virus, wheat spindle streak virus, wheat streak virus; (b) a group of viruses which are transmitted by eriophyid mites: e.g., Agropyron mosaic virus, oat necrotic mottle virus, ryegrass mosaic virus, Spartina mottle virus, wheat streak mosaic virus; (c) the whitefly-transmitted virus sweet potato mild mottle virus; and (d) a group of viruses transmitted by Polymyxa graminis: barley yellow mosaic virus, oat mosaic virus, rice necrosis mosaic virus, wheat spindle streak mosaic virus, wheat yellow mosaic virus. Some or all of these ‘possible members’ may actually belong to or constitute separate groups. pouch (food processing) See RETORT POUCH. poultry diseases Poultry (chickens, ducks, turkeys, etc) can be affected by a wide range of diseases – some specific for one species of bird, others affecting a range of birds. (a) Bacterial diseases: see e.g. AIR SACCULITIS; ARIZONOSIS; BUMBLEFOOT; COLISEPTICAEMIA; DIPHTHEROID STOMATITIS; erysipelas (see ¨ SWINE ERYSIPELAS); FOWL CHOLERA; FOWL TYPHOID; HJARRE’S DISEASE; PSITTACOSIS; PULLORUM DISEASE. (b) Fungal diseases: see e.g. ASPERGILLOSIS; CANDIDIASIS; FAVUS. (c) Protozoal diseases: see e.g. BLACKHEAD; COCCIDIOSIS; HEXAMITIASIS. (d) Viral diseases: see e.g. AVIAN ACUTE LEUKAEMIA VIRUSES; AVIAN ENCEPHALOMYELITIS; AVIAN INFECTIOUS BRONCHITIS; AVIAN INFECTIOUS LARYNGOTRACHEITIS; AVIAN RETICULOENDOTHELIOSIS VIRUSES; AVIAN SARCOMA VIRUSES. DUCK VIRUS ENTERITIS; DUCK VIRUS HEPATITIS; FOWL PLAGUE; FOWL POX; HAEMORRHAGIC ENTERITIS OF TURKEYS; INCLUSION BODY HEPATITIS; INFECTIOUS BURSAL DISEASE VIRUS; LYMPHOID LEUKOSIS; MAREK’S DISEASE; NEWCASTLE DISEASE; OSTEOPETROSIS. (See also EGG-DROP SYNDROME, PARVOVIRUS and STUNTING SYNDROME.) (e) Diseases due to ingestion of microbial toxins include e.g. LIMBERNECK; TURKEY X DISEASE; WESTERN DUCK DISEASE. poultry spoilage See MEAT SPOILAGE. pour plate (1) A procedure (used e.g. as a COUNTING METHOD) in which a measured volume of liquid INOCULUM is placed in a PETRI DISH, a molten medium (e.g. an agar medium at 45–48° C) is added, and the whole swirled to disperse the inoculum throughout the medium; when set, the plate is incubated. (The inoculum may instead be mixed with the medium before the latter is poured into the Petri dish.) The medium may incorporate a reducing agent (e.g. sodium thioglycollate) so that even under aerobic incubation some anaerobes can grow within the medium. (2) A CULTURE prepared as in (1). pourriture noble (French) syn. NOBLE ROT. povidone–iodine See IODINE (a). POW virus See POWASSAN ENCEPHALITIS. Powassan encephalitis An acute, occasionally fatal, human ENCEPHALITIS caused by a flavivirus (see FLAVIVIRIDAE); it occurs e.g. in forested areas of Canada and Northern USA. The Powassan virus (POW virus) occurs in small mammals and is transmitted by ticks (usually Ixodes spp). [ARE (1981) 26 84–85.]

premature death (see also RUGOSE MOSAIC DISEASE). PVY YC strains may cause necrosis, mottling, crinkling, and necrotic streaks on leaves, petioles and stem; necrosis may occur in the tubers. Symptoms of PVY infection in capsicum, tobacco and tomato typically include mild mottling, but YN strains can cause a severe disease in tobacco (‘tobacco veinal necrosis disease’) which may result in total loss of the crop. potato yellow dwarf virus See RHABDOVIRIDAE. Poterioochromonas See OCHROMONAS. potexviruses (potato virus X group) A group of PLANT VIRUSES in which the virions are flexuous filaments (ca. 470–580 ð 13 nm) comprising one type of coat protein (MWt ca. 18000–23000) and one molecule of linear positive-sense ssRNA (MWt ca. 2.1 ð 106 ). The RNA is capped at the 50 end 0 (sequence: m7 G5 pppGpA . . .) but is not polyadenylated at the 30 end; the adenine content of the RNA is ca. 30%. The host range for the group is wide, including monocots and dicots, but individual members infect only a narrow host range. Plants infected with potexviruses typically develop mosaic and ringspot symptoms. Virus particles form fibrous, sometimes banded, often large aggregates in the cytoplasm of infected cells; some members also induce nuclear inclusions. Transmission occurs mechanically. Type member: potato virus X (PVX). Other members include e.g. cactus virus X, cassava common mosaic virus, clover yellow mosaic virus, Cymbidium mosaic virus, Papaya mosaic virus, Plantago severe mottle virus, Plantago virus X, white clover mosaic virus. Possible members include e.g. artichoke curly dwarf virus, bamboo mosaic virus, barley B-1 virus, Boletus virus, negro coffee mosaic virus, potato aucuba mosaic virus. Potomac horse fever (equine monocytic ehrlichiosis) A HORSE DISEASE caused by Ehrlichia risticii, a species antigenically related to E. canis and E. sennetsu (and which can be transmitted, experimentally, to cattle [VR (2001) 148 86–87]). Symptoms are variable, and may include e.g. fever, depression, anorexia, colic, mild to severe diarrhoea, oedema, etc; mortality rates may exceed 30%. Potter–Elvehjem homogenizer A type of blender used e.g. for preparing subcellular fractions of eukaryotic cells. Pott’s disease Tuberculosis of the spine – see OSTEOMYELITIS. potyviruses (potato virus Y group) A large group of PLANT VIRUSES in which the virions are flexuous filaments (ca. 680–900 ð 11 nm) comprising one type of coat protein (MWt ca. 32000–36000) and one molecule of linear positive-sense ssRNA (MWt ca. 3.0–3.5 ð 106 ). As a group, the viruses infect a wide range of host plants, including monocots and dicots, but individual members typically have a narrow host range; some members can cause important economic losses in crop plants. Symptoms depend on plant cultivar, virus strain, and environmental conditions, but typically include mosaic or mottle in the leaves, colour-breaking in flowers, mottling and/or distortion in the fruits; characteristic proteinaceous inclusion bodies (serologically unrelated to virus coat protein) are formed in the cytoplasm of infected plant cells, appearing as ‘pinwheels’ in transverse section or as ‘bundles’ in longitudinal section. A few members also form crystalline nuclear inclusions. Potyviruses are transmitted (non-persistently) by aphids (see NON-CIRCULATIVE TRANSMISSION sense 1) and can be transmitted mechanically; some viruses tentatively included in the group are transmitted by whitefly, mites or fungi. Type member: POTATO VIRUS Y. Other members include e.g. bean common mosaic virus, bean yellow mosaic virus (of which pea mosaic virus is a strain), beet mosaic virus, blackeye cowpea 607

powdery mildews powdery mildews Plant diseases caused by members of the ERYSIPHALES and characterized by the formation of at least partially superficial hyphal growth carrying a dense layer of conidia in which individual conidium-bearing structures are difficult to distinguish under low magnification (cf. DOWNY MILDEWS); dark-coloured cleistothecia may develop among the hyphae during the summer – being the overwintering stage in some species. Powdery mildews of cereals (including barley and wheat) are caused by Erysiphe graminis. White to grey (later brownish) mycelium develops on small chlorotic spots on leaves, and may also occur on the glumes (particularly in wheat); lodging may occur. Control: antifungals such as CARBENDAZIM and PROCHLORAZ. powdery scab A POTATO DISEASE caused by Spongospora subterranea (PLASMODIOPHOROMYCETES). Small wart-like swellings develop on the stolons, roots and tubers of infected plants; a dry brownish powder (consisting of masses of cystosori) forms within the tuber lesions. The cysts can persist in the soil for many years. The disease is favoured by wet soil conditions. The pathogen can also infect tomato roots. powdery yeasts See FLOCCULATION (sense 2). pOX1 plasmid See ANTHRAX TOXIN. pOX2 plasmid See ANTHRAX TOXIN. Poxviridae (the poxvirus group) A family of dsDNA-containing VIRUSes which infect mammals (including man), birds or insects; some members are important pathogens (e.g. the causal agents of SMALLPOX, MONKEYPOX, CONTAGIOUS PUSTULAR DERMATITIS (sense 1), etc). The family includes two subfamilies, CHORDOPOXVIRINAE (vertebrate poxviruses) and ENTOMOPOXVIRINAE (insect poxviruses), together with several unclassified viruses (e.g. MOLLUSCUM CONTAGIOSUM virus, TANAPOX VIRUS, YABA MONKEY TUMOUR POXVIRUS) [Book ref. 23, pp. 42–46]. The poxvirus virion is the largest and structurally the most complex of all animal viruses. Depending on virus, it may be ovoid or brick-shaped, ca. 200–450 ð 170–260 nm. It contains a central core (incorporating the genome) which is commonly bilaterally concave; on either side of the core – coincident with each concavity – is an ellipsoidal structure called the lateral body. (cf. ENTOMOPOXVIRINAE.) The core and its two associated lateral bodies are enclosed within a lipoprotein outer membrane which bears a characteristic pattern of ridges or tubules on its surface. (In some poxviruses the extracellular virions have an extra lipoprotein layer, the envelope, acquired from the host cell; these are believed to be the infective forms of the virus.) The virion contains a variety of enzymes, including enzymes involved in e.g. DNA replication, transcription, and RNA processing. In general, poxvirus virions are stable at room temperature and are resistant to desiccation; most are etherresistant but may be inactivated e.g. by chloroform and by heating (e.g. 60° C/20 min). The genome is a single molecule of dsDNA (MWt in the range 85–250 ð 106 ) in which – in at least some poxviruses – the two strands are covalently joined at each end of the molecule (i.e., the molecule is actually a single uninterrupted circular polynucleotide chain). The genome contains highly conserved sequences in the central region, and terminal hypervariable regions. [Genomes: orf virus, bovine papular stomatitis virus [JV (2004) 78 168–177]; goatpox, sheeppox [JV (2002) 76 6054–6061]; deerpox [JV (2005) 79 966–977.] Replication cycle. Poxvirus replication occurs in the cytoplasm of the host cell; studies on replication processes have been carried out mainly with orthopoxviruses (particularly VACCINIA

VIRUS).

Infection begins when the virion adsorbs to a host cell; vaccinia virus appears to bind to the host cell-surface epidermal growth factor (EGF) receptor [Nature (1985) 318 663–665]. The virus apparently enters the cell by fusion between viral and cell membranes and/or by viropexis. An early consequence of infection is the inhibition of host cell DNA, RNA and protein synthesis [review: Book ref. 150, pp. 391–429]. The viral core is uncoated in the cytoplasm, and enzymes of the core begin transcription of the viral DNA; early mRNA is synthesized by an a-amanitin-resistant viral RNA polymerase, and viral enzymes then process the RNA to form the functional polyadenylated, capped and methylated mRNA. (Early mRNAs, at least, are apparently not spliced.) DNA replication then begins; this may involve nicking of the DNA to provide free 30 -ends which can act as primers. The onset of DNA replication allows initiation of the synthesis of late mRNA which codes for most of the structural proteins of the virion. Proteolytic processing of the structural proteins appears to be coupled to virus assembly. In the case of vaccinia virus, the mature virions each become enclosed in a double membrane derived from the Golgi apparatus and are transported to the cell periphery; it was suggested that the outer viral membrane may fuse with the cell membrane, resulting in the release of virions enclosed by a single layer of Golgi membrane [JGV (1985) 66 643–646]. The discrete cytoplasmic sites of virus replication are termed ‘virus factories’, ‘factory areas’, or ‘viroplasms’; they are visible in suitably stained preparations as B-type inclusion bodies (D GUARNIERI BODIES). Some poxviruses (e.g. COWPOX VIRUS) form a second type of inclusion body, the A-type inclusion body: acidophilic structures which may or may not contain virions. poxvirus group See POXVIRIDAE. pp Prefix denoting (1) phosphoprotein (see e.g. RETROVIRIDAE), or (2) diphospho- or pyrophospho- (as in ppGpp). PPAR Peroxisome proliferator-activated receptor: see PROSTAGLANDINS. PPD See TUBERCULIN. PPFM Pink-pigmented facultatively methylotrophic bacterium. ppGpp See (i) CELL CYCLE; (ii) STRINGENT CONTROL (sense 1); and (iii) SPOT GENE. ppGpp has been classified as an ALARMONE. PPi Inorganic PYROPHOSPHATE (P2 O7 4
). PPLOs Pleuropneumonia-like organisms: an early name for Mycoplasma spp. PQQ See QUINOPROTEIN. Pr Prefix denoting a polyprotein product of transcription (see e.g. RETROVIRIDAE). PR proteins PATHOGENESIS-RELATED PROTEINS. Pr65 gag precursor protein (of FeLV) See FELINE LEUKAEMIA VIRUS. PRAS media Pre-reduced anaerobically-sterilized media. Prasinocladus See TETRASELMIS. Prasinomonadida See PHYTOMASTIGOPHOREA. Prasinophyceae A class of unicellular, flagellated green algae which have scaly flagella arising from an anterior flagellar pit. The class, which is no longer recognized [Book ref. 123, pp. 65–66], included e.g. TETRASELMIS and many of the genera in the MICROMONADOPHYCEAE. Prasiola A genus of marine and freshwater green algae (division CHLOROPHYTA). The thallus is foliose or filamentous. Asexual reproduction occurs by the formation of diploid aplanospores. In at least some species sexual reproduction is preceded by meiosis in the cells of the upper portion of the blade followed by several mitotic divisions; this results in the formation of 608

Pribnow box prephenate See AROMATIC AMINO ACID BIOSYNTHESIS. preprimosome See PRIMOSOME. pre-protein See SIGNAL HYPOTHESIS. pre-reduced medium See ANAEROBE. preservation (1) (of materials, products) The use of physical and/or chemical means to kill or prevent the growth of those microorganisms which, by their growth and/or activities, may cause BIODETERIORATION of a given material or product. Physical methods (e.g. heat STERILIZATION, freezing – see e.g. FOOD PRESERVATION) either kill contaminating organisms or render the materials or products unsuitable for the (rapid) growth of likely contaminants. Chemical agents (PRESERVATIVES) may be microbistatic or microbicidal. (2) (of microorganisms) Viable populations of microorganisms may be preserved (i.e. maintained for reference purposes etc) by e.g. FREEZING, FREEZE-DRYING or DESICCATION. Some bacterial cultures can be preserved by sealing with a layer of sterile mineral oil and storing at ca. 4° C. A culture may be preserved by periodic SUBCULTURE (see also STABILATE). preservative Any chemical used for the PRESERVATION of materials or products; in some industries such chemicals are referred to as BIOCIDES. For examples of preservatives and their usage see e.g. FOOD PRESERVATION, PAINT SPOILAGE, PAPER SPOILAGE, SAUSAGE, TEXTILE SPOILAGE, TIMBER PRESERVATION; see also ALCOHOLS, BISPHENOLS, CHLORBUTANOL, EGME, FORMALDEHYDE, GERMALL 115, PHENOLS, QUATERNARY AMMONIUM COMPOUNDS, SALICYLANILIDES, THIOMERSAL. A preservative may be inactivated e.g. by colloids (such as magnesium trisilicate or bentonite – cf. BENZOIC ACID; CHLORBUTANOL) or by certain container materials (polyethylene can inactivate e.g. dichlorophenol and other phenolics, while polypropylene can inactivate e.g. dichlorophenol and sorbic acid). prespore See ENDOSPORE (sense 1(a)). pressure-cycle fermenter See AIRLIFT FERMENTER. presumptive coliform count See COLIFORM TEST. pretibial fever Syn. FORT BRAGG FEVER. pretrichocyst See TRICHOCYST. pretyrosine See AROMATIC AMINO ACID BIOSYNTHESIS. Prevotella A genus of Gram-negative, asporogenous, anaerobic, rod-shaped bacteria found e.g. in the human oral cavity; some species form black or brown pigments when grown on bloodcontaining media. Most species ferment sucrose and lactose. Using quantitative culture on a non-selective blood-agar medium, studies on the anaerobic oral microflora in the first year of life found that organisms in the Prevotella melaninogenica group were among the early colonizers (18% at 2 months, rising to 57% at 6 months and 77% at 12 months); members of the P. intermedia group were apparently late colonizers, whereas isolation of non-pigmented species of Prevotella increased from ‘occasional’ at 2 months to 75% at 12 months [RMM (1997) 8 (supplement 1) S19–S20]. Species of Prevotella have been associated with e.g. abscesses and PERIODONTITIS. [Simultaneous detection of Prevotella intermedia and Bacteroides forsythus by multiplex PCR in clinical samples: JCM (1999) 37 1621–1624.] pre-zygotic exclusion During processes such as CONJUGATION (sense 1b) and TRANSDUCTION: the absence of expression of a given donor gene in the recipient as a result of the failure of that gene to enter the recipient. If the gene entered the recipient but failed to recombine with the recipient’s genome, the absence of expression of that gene is referred to as post-zygotic exclusion. prgI gene (Salmonella typhimurium) See NEEDLE COMPLEX. Pribnow box See PROMOTER.

polystromatic micro- and macrogametangial regions which give rise to biflagellate microgametes and non-motile macrogametes, respectively. Prausnitz–Kustner antibodies Syn. REAGINIC ANTIBODIES. ¨ Prausnitz–Kustner test (P–K test) A test used for demonstrat¨ ing the presence of IgE antibodies homologous to a given allergen. Serum from a hypersensitive subject is injected intradermally into a normal subject; subsequent injection of the normal subject with the given allergen causes a WHEAL-AND-FLARE response to develop within minutes (a positive test). The P–K reaction can be inhibited by the prior injection of a fragment of e-chain [Nature (1985) 315 577–578]. PRD See CATABOLITE REPRESSION. PRD1 phage group Syn. TECTIVIRIDAE. preaxostyle See OXYMONADIDA. pre-B cell See B LYMPHOCYTE. prebiotic (1) A non-digestible part of a food (often an oligosaccharide) which, by selectively stimulating certain type(s) of colon bacteria, benefits the host. (2) (adj.) The time before life appeared on Earth. prebuccal area In some ciliates (e.g. Paramecium): a depression in the body surface leading to the BUCCAL CAVITY; its ciliature is essentially somatic (cf. VESTIBULUM). precipitation (serol.) The formation of a precipitate when antibodies and soluble antigens react in suitable proportions (see e.g. OPTIMAL PROPORTIONS; cf. ANTIGEN EXCESS and AGGLUTINATION). (See also GEL DIFFUSION.) precipitin An ANTIBODY which forms a precipitate with its homologous soluble antigen. (cf. AGGLUTININ.) precipitin test Any serological test in which the interaction of antibodies with soluble antigens is detected by the formation of a precipitate. precipitinogen (1) An antigen which elicits a PRECIPITIN. (2) Any agent (e.g. PROTEIN A) which can combine with antibody to form a precipitate. precyst See CYST (a). prednisone See IMMUNOSUPPRESSION. pre-erythrocytic schizogony (in Plasmodium) See PLASMODIUM. pre-filtration See FILTRATION. pre-fixation See FIXATION. pre-genome See HEPADNAVIRIDAE. pregnancy test An IMMUNOASSAY in which urine is examined for human chorionic gonadotrophin (hCG), a hormone that appears during pregnancy. Urine is added to serum containing antihCG antibodies, which combine with hCG. Then, the absence of uncombined antibodies (a positive test) is shown by nonagglutination when latex-bound hCG is added. pre-initiation complex See PROMOTER. Preisz–Nocard bacillus See CORYNEBACTERIUM. pre-lesion terminus In damaged DNA: the nucleotide immediately 50 of the lesion site. premunition (concomitant immunity; non-sterilizing immunity) (immunol.) Protective immunity, in respect of a given pathogen, due to the persistence of small numbers of that pathogen in the host; the host can resist superinfection (i.e., infection by the same or closely related pathogens) but cannot achieve STERILIZING IMMUNITY. In an apparently analogous phenomenon, cells of a given tumour type fail to develop when injected into an animal suffering from the same type of tumour. ` ´ preoral suture See SYSTEME SECANT . prepatent period In a parasitic infection: the time interval between the initial infection and the appearance of parasites, or their cysts, in blood, tissues or faeces. 609

Pril Pril A quaternary ammonium detergent used e.g. in certain media to prevent swarming by Proteus spp. prill A solid in granular form. primaquine See MALARIA (chemotherapy). primary amoebic meningoencephalitis See MENINGOENCEPHALITIS. primary atypical pneumonia (1) Any of a group of pneumonias characterized by symptoms distinct from those of ‘classical’ lobar PNEUMONIA and by a causal agent which cannot readily be isolated by routine laboratory methods; the group includes LEGIONELLOSIS; Mycoplasma pneumoniae pneumonia (see (2) below); PSITTACOSIS; Q FEVER. (2) PNEUMONIA caused by Mycoplasma pneumoniae; it affects mainly children. Infection occurs by droplet inhalation. Incubation period: 2–3 weeks. Onset is insidious, with fever and malaise followed by symptoms of an upper respiratory tract infection; a persistent, non-productive cough typically develops, and ear infection is common. The disease is usually mild and self-limiting, with few chest signs; in only a minority of cases does frank pneumonia develop. Chemotherapy: e.g. erythromycin. primary constriction Syn. CENTROMERE. primary culture (1) A CULTURE prepared by inoculating a medium directly from a natural source of microorganisms (cf. SUBCULTURE). For example, a bacteriological medium may be inoculated directly from a faecal specimen. In TISSUE CULTURE a primary culture is one prepared from cells or tissues taken directly from an animal or plant. (2) The process of preparing a culture as in (1). primary fixation Syn. pre-FIXATION. primary fluorescence See FLUORESCENCE. primary host (of rust fungi) See UREDINIOMYCETES. primary hyphae See HYPHA. primary metabolism Metabolism which is essential for and geared towards growth – i.e., energy metabolism, synthesis of cell components, etc. (cf. SECONDARY METABOLISM.) primary mycelium (in actinomycetes) Syn. SUBSTRATE MYCELIUM. primary production The production of new biomass by photosynthetic organisms as a result of their use of light (solar) energy. The phrase ‘chemosynthetic primary production’ has been used to refer to the production of biomass by those nonphotosynthetic organisms which are believed to derive energy from the oxidation of e.g. sulphide and/or methane in the vicinity of HYDROTHERMAL VENTS in the ocean floor; these organisms (which include species of Thiobacillus and Thiomicrospira) appear to be at the start of a food chain which is unique in that it is not based on photosynthetic organisms. primary septum See SEPTUM (b). primary zoospore See e.g. DIPLANETISM and PLASMODIOPHOROMYCETES. primase (DNA primase) An enzyme which, in vitro, can polymerize molecules of ribonucleoside triphosphate (rNTPs) and/or dNTPs in the 50 -to-30 direction to form short oligonucleotides on an ssDNA template. In vivo, Escherichia coli primase (dnaG gene product) synthesizes short RNA primers for the formation of Okazaki fragments in DNA REPLICATION, and also synthesizes primers for the initiation of DNA replication of isometric ssDNA phages. Primase either recognizes a specific region of DNA directly (as in BACTERIOPHAGE G4) or, more commonly, it requires the co-operation of additional proteins (see PRIMOSOME). Certain phages (e.g. T4, T7) encode their own primases. Primase action is resistant to rifampicin (cf. RNA POLYMERASE).

primate T-cell leukaemia virus See SIMIAN T-CELL LEUKAEMIA VIRUS. prime plasmid A PLASMID which has undergone aberrant excision from a bacterial chromosome. In some types of prime plasmid (‘type I’), part of the plasmid has been left behind in the chromosome, and the plasmid carries a sequence of bacterial DNA; a ‘type II’ prime plasmid consists of the entire plasmid carrying a sequence of bacterial DNA. The particular sequence of bacterial DNA carried by a prime plasmid depends on the site within the chromosome occupied by the plasmid before excision; thus, e.g. it is possible to isolate various F0 plasmids (derived from the F PLASMID) because this plasmid can integrate at various sites in the bacterial chromosome. (See also specialized TRANSDUCTION.) primed (immunol.) (1) (of persons, animals) Refers to those individuals who have had an initial immunological contact with a given antigen; such individuals may respond e.g. with ANTIBODY FORMATION. Subsequent exposure of a primed individual to the given antigen may bring about a heightened response (see ANAMNESTIC RESPONSE and HYPERSENSITIVITY (sense 1)). (See also IMMUNE RESPONSE.) (2) (of cells) Refers to those cells whose responsiveness to a given antigen has been heightened as a consequence of their previous contact with that antigen (or of previous contact between their precursor cells and that antigen). (cf. PRIMING.) primer See (i) DNA REPLICATION; (ii) PCR; (iii) NASBA; (iv) SDA; and (v) FORWARD PRIMER. primer-dimer In a PCR reaction mixture: an artefact resulting from the use of a pair of primers whose 30 terminal sequences are mutually complementary; during extension, each primer uses the other as a template – forming products that consist essentially of two double-stranded primers in tandem. priming (1) (mol. biol.) The initiation of synthesis of a DNA strand e.g. by the synthesis of an RNA primer (see DNA REPLICATION). (For ‘specific’ and ‘general’ priming see DNAB GENE.) (2) (immunol.) The process in which an individual becomes PRIMED. primite The anterior organism of a pair of gregarines in SYZYGY. (cf. SATELLITE.) primociliatid gymnostomes Presumptively primitive ciliates (subclass GYMNOSTOMATIA, order Primociliatida) which are homokaryotic; species of STEPHANOPOGON are the only known examples. primordium (microbiol.) Syn. INITIAL(s). primosome A multiprotein complex involved in certain cases of primer synthesis (see DNA REPLICATION): e.g. in BACTERIOPHAGE fX174 DNA synthesis, and in Okazaki fragment synthesis during Escherichia coli chromosome replication and e.g. COLE1 PLASMID replication. Primosome formation on ssDNA coated with SINGLESTRAND BINDING PROTEIN is initiated by protein n0 (D factor Y) which recognizes and binds to specific short base sequences in the DNA. In the presence of ATP, a complex of DnaB (see DNAB GENE) and DnaC proteins is formed which, together with proteins i (D factor X), n, and n00 combine with n0 to form a prepriming intermediate (preprimosome) at or near the n0 recognition site. The preprimosome is recognized and bound by the DnaG protein (PRIMASE) to complete the primosome. The primosome migrates along the ssDNA template in a 50 -to-30 (anti-elongation) direction (i.e., in the direction of replication fork movement in dsDNA replication), driven by ssDNAdependent ATP hydrolysis by n0 , and primase synthesizes short RNA primers at many different sites on the template DNA. The 610

probe direction of primase action is opposite to that of primosome migration; primer synthesis is assumed to occur within the domain of the primosome. [JBC (1981) 256 5273–5286.] primulin A polycyclic fluorescent dye. (See also SCAR.) prion (1) In man/animals: an aberrant form of a normal, chromosome-encoded glycoprotein; prions are now believed to be the aetiological agents of TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES. [Mapping the parameters of prion-induced neuropathology: PNAS (2000) 97 10573–10577.] The normal protein, which is designated PrPc , is encoded (in humans) by the PRNP gene (on chromosome 20). PrPc is a component of the cytoplasmic membrane in certain types of cell – e.g. neurones, astrocytes, dendrocytes, lymphocytes and macrophages. Synthesis of PrPc involves intranuclear transcription of PRNP and translation on the endoplasmic reticulum; post-translational modification includes glycosylation (although some molecules remain unglycosylated) and attachment to a glycolipid phosphatidylinositol (GPI) ‘anchor’. The PrPc molecule is apparently anchored at the cell surface for a short period of time and then internalized and degraded in a lysosome. The function of PrPc has not been established. When a prion infects a cell, it appears that normal breakdown of (at least some) PrPc does not occur, and that the secondary structure of these PrPc molecules is changed to that of the prion. This is thought to occur either by interaction between individual PrPc and prion molecules (heterodimer model), or by interaction between individual PrPc molecules and organized aggregates of prion molecules (the ‘seed’ or ‘nucleus’ model). Accumulation of prions in the form of crystalloid structures eventually leads to the death of the cell. (Interestingly, specific parts of PrPc (particularly the central region: residues 90–120) undergo spontaneous re-arrangement to a conformation resembling that of the infectious form when immobilized on a surface with recombinant antibodies [EMBO (2001) 20 1547–1554].) In the prion model of pathogenesis, prions may be present through infection – either via ingestion (as in KURU) or through their introduction by medical or surgical procedures. The inherited prion diseases, in which the PRNP gene is almost invariably heterozygous (wild-type and mutant alleles), are believed to result from the effect of mutant (prion) proteins on wild-type proteins. In the so-called ‘sporadic’ prion diseases, conversion of normal protein to prion protein is considered to result e.g. from random, spontaneous events. The presence of normal (PrPc ) protein appears to be necessary for the development of prion diseases: knockout mice which are unable to form PrPc do not develop disease on challenge with prion-containing tissue; this suggests that a prion cannot direct the production of further prions without a supply of the normal protein. Prions do not differ, biochemically, from the normal protein, i.e. the amino acid sequence is identical. However, the conformation is different: about ¾40% of normal protein is in the soluble, protease-sensitive a-helical state – with little or no bsheet formation; in contrast, the prion form (isoform) is insoluble and protease-resistant, and is composed of ¾50% b-sheet and ¾20% a-helix forms. (See also PLASMINOGEN.) Prions are resistant to e.g. heat, ionizing and ultraviolet radiation, formalin, b-propiolactone and bleach (as well as to proteases). The prion form of PrPc is often designated PrPres (indicating resistance). Some authors use PrPsc (which, strictly, indicates the SCRAPIE prion) as a generalized designation for any prion;

others use superscripts which indicate the specific disease (e.g. ‘GSS’ for Gerstmann–Str¨aussler–Scheinker syndrome). [Protein misfolding in prion disease: Cell (1997) 89 499–510; human prion diseases: Book ref. 215, pp. 39–77.] (2) Strains of the yeast Saccharomyces cerevisiae contain a protein release factor (see PROTEIN SYNTHESIS) designated eRF3 (D Sup35, product of gene SUP35 ) which, through variation in its effective concentration in the cytoplasm, can influence the fidelity with which translation is terminated on the ribosome; thus, a lowered concentration of the release factor promotes readthrough at certain stop codons. A non-genetic mechanism which can control the concentration of eRF3 may therefore permit heritable variation in the organism without changes in the genome [see e.g. Nature (2000) 407 477–483]. Sup35 can exist in an aggregated, prion form (the [PSIC ] state) or in a soluble form (the [psi
] state). In [PSIC ] cells, aggregation of Sup35 protein reduces the amount available for terminating translation on the ribosomes, and this allows readthrough at certain stop codons. Propagation of [PSIC ] involves protein–protein interaction following the mixing of cytoplasm from different cells (e.g. during mating); in this process the soluble form of Sup35 is converted to the aggregated (prion) form. (Interestingly, if a [PSIC ] strain of S. cerevisiae is grown in the presence of 2 M glycerol (or certain other agents) the aggregates of Sup35 break down to the soluble form of Sup35, i.e. a [psi
] strain of the yeast is formed.) [Elimination of [PSIC ] by guanidine hydrochloride: Mol. Microbiol. (2001) 40 1357–1369.] [eRF3 concentration in the termination of translation: Microbiology (2001) 147 255–269 (262–263).] In vitro studies involving fusion between the prion domain of Sup35 proteins from S. cerevisiae and Candida albicans may help to explain factor(s) which determine the ability of a prion to cross a species barrier [Nature (2001) 410 223–227]. pristane An isoprenoid alkane: 2,6,10,14-tetramethylpentadecane. pristinamycins See STREPTOGRAMINS. pRNA See BACTERIOPHAGE f29. PRNP gene See PRION. probasidium (1) A developing BASIDIUM at the stage at which karyogamy occurs; in many basidiomycetes the terms probasidium and METABASIDIUM refer to the same structure at different developmental stages. (2) That part of a developing basidium in which karyogamy occurs – e.g. the teliospore (or its contents) of the rust and smut fungi, or, in Septobasidium, the typically thick-walled structure from which arises, by outgrowth, the septate, basidiosporebearing metabasidium. probe A short strand of DNA or RNA (often 10–25 nucleotides in length) which is complementary to a given target sequence of nucleotides; because a probe can hybridize specifically with its target sequence, it can be used e.g. to detect, identify or locate the target. To make the probe detectable it is ‘labelled’ either before or after it hybridizes to the target sequence (see below). (In addition to DNA or RNA, probes may also be prepared from PNA [JAM (2001) 90 180–189].) Probe–target hybridization is affected e.g. by temperature, pH and concentration of electrolyte. Conditions can be chosen such that the probe will hybridize only to the exact target sequence, i.e. conditions under which mis-matches are not tolerated; such high-stringency conditions are used to promote specificity in probe–target binding. Under low-stringency conditions the effect of mis-matched base(s) can be minimized so 611

probenecid that hybridization may occur even when the probe–target duplex contains mis-matched base(s). The detection of RNA targets may be achieved with greater rapidity and specificity by means of 20 -O-methyl oligoribonucleotide probes (compared with 20 -deoxy oligoribonucleotide probes) [NAR (1998) 26 2224–2229]. Labelling of probes. Probes may be labelled directly and covalently with radioactive isotopes (e.g. 32 P); such isotopic labels can be detected by autoradiography. Both DNA and RNA probes can be labelled at the 50 end with e.g. [g32 P]ATP (i.e. ATP with 32 P in the g position); this reaction is mediated by polynucleotide kinase. Radioactive labels are robust, and are associated with good sensitivity (but limited resolution). Non-radioactive (non-isotopic) labelling with e.g. enzymes or fluorescent molecules is common. Labelling may be either direct or indirect. Thus, for example, existing probes may be labelled with a reactive fluorophore which binds covalently to the probe; such labelling systems are available commercially (e.g. FluoReporter , marketed by Molecular Probes Inc., Eugene, OR, USA). In the second form of direct fluorescent labelling, probes are synthesized in a reaction mixture containing fluorophore-conjugated nucleotides (which are thus incorporated into the probe). Such fluorescent nucleotides are available commercially (e.g. ChromaTide ; Molecular Probes Inc.). Fluorescent labels are detected by examining the preparation under ultraviolet light. CHEMILUMINESCENCE is used in probe detection in certain commercial diagnostic tests (see e.g. hybridization protection assay in the entry TMA). Note that, in direct labelling, the probe is already labelled prior to hybridization. For indirect labelling (e.g. with an enzyme or fluorophore), a small molecule (e.g. a biotin or DIGOXIGENIN ‘tag’) is incorporated into the probe before use. After hybridization, the probe is detected by using a conjugate to link the tag with a fluorophore or enzyme – see e.g. DOT-BLOT. (It has been reported that short (¾10-nucleotide) 50 -biotinylated probes give satisfactory results when labelled with a STREPTAVIDIN –alkaline phosphatase conjugate prior to the hybridization step [NAR (1999) 27 703–705].) Uses of probes. Probes can be used e.g. to detect, identify or locate particular pathogens in clinical specimens (by demonstrating the presence of pathogen-specific sequences); specimens are commonly subjected to pre-test procedures in which any target nucleic acids that may be present are exposed (in singlestranded form) to specific probes. One example is the PACE 2C test (Gen-Probe, San Diego, USA) which, in a single assay, can detect Chlamydia trachomatis and/or Neisseria gonorrhoea in urogenital specimens [see e.g. JCM (1995) 33 2587–2591]. In situ hybridization (ISH) involves the use of strain- or species-specific probes e.g. for detecting pathogens in situ – i.e. at the actual site of infection within tissues or cells; bacterial, viral, fungal and protozoal pathogens may be detected. ISH is particularly useful for demonstrating nucleic acids which are focally distributed – e.g. virus-infected tissue. For example, ISH was found to be as sensitive as PCR for the detection of human papillomavirus in cervical scrapings [HJ (1995) 27 54–59]. Much of the early work in ISH was conducted with radioactive probes; currently, fluorescent probes are common (fluorescence in situ hybridization: FISH). FISH is both rapid and flexible. For example, the target area can be interrogated simultaneously with several different types of probe (each labelled with a different fluorophore); thus, when different probes bind to closely adjacent targets they can be distinguished by their emission characteristics.

Probes are also used in a line probe assay for detecting certain point mutations which confer resistance to antibiotics in Mycobacterium tuberculosis. Essentially, PCR is used to amplify a sequence in the chromosome associated with common resistance-conferring mutations, and the amplicons are denatured to the single-stranded state; these products are then tested for hybridization against a range of probes which include nonmutant and mutant copies of the given chromosomal sequence. The presence/absence of hybridization between the amplicons and each of the probes provides an indication of the probable resistance or susceptibility of the test strain to given antibiotic(s). [Evaluation of a line probe assay: JCM (1997) 35 1281–1283.] In nucleic acid amplification processes, specialized probes can provide a real-time indication of progress in the reaction, and can also be used to assess the concentration of target molecules present in the sample prior to amplification (see TAQMAN PROBES). (See also MOLECULAR BEACON PROBES.) [Probe-based methods in clinical microbiology: Book ref. 221, pp 44–55.] probenecid A drug which e.g. delays the excretion of – and (thus) helps to maintain blood levels of – certain penicillins and cephalosporins. Probenecid, which inhibits glucuronidation, may affect the metabolism of the antiretroviral drug AZT. probiotic Any potentially beneficial preparation consisting typically of a culture of bacteria (or bacterial spores) of a type normally found in the healthy gut microflora. Oral administration of probiotics has been reported to restore normal gut microecology and e.g. to enhance intestinal IgA responses; perinatal and postnatal administration of the probiotic Lactobacillus rhamnosus (D Lactobacillus GG; ATCC 53103) has been associated with a significant reduction in the incidence of atopic disease (eczema) in at-risk infants [Lancet (2001) 357 1076–1079; see also commentary: Lancet (2001) 357 1057–1059]. The Shirota strain of Lactobacillus casei is reported to be useful therapeutically against an Escherichia coli urinary tract infection when administered intraurethrally [AAC (2001) 45 1751–1760]. Probiotic activity has been reported for various strains of Bacillus. For example, the product Enterogermina (an aqueous suspension of spores) is used in Italy with the object of preventing or treating bacterial diarrhoea. [Molecular characterization of bacteria (Bacillus clausii ) from samples of Enterogermina: AEM (2001) 67 834–839.] (See also YAKULT and VSL#3; cf PREBIOTIC.) procapsid A capsid precursor formed during the assembly of a virus. Procaryotae An obsolete kingdom which comprised the PROKARYOTES; proposed divisions of the Procaryotae: FIRMICUTES; GRACILICUTES; MENDOSICUTES; TENERICUTES. procaryote Syn. PROKARYOTE. processive enzyme An enzyme which binds to a (macromolecular) substrate and then moves along it, functioning as it goes. (See e.g. HELICASES; DNA POLYMERASES.) Prochlorales See PROCHLOROPHYTES. prochloraz (trade name: e.g. Sportak) An agricultural systemic ANTIFUNGAL AGENT which inhibits sterol biosynthesis, thereby disrupting the cytoplasmic membrane in susceptible fungi. It is used e.g. against rhynchosporium, net blotch and powdery mildew of cereals, and – mixed with e.g. mancozeb – for the control of yellow rust (Puccinia striiformis) on wheat. Mixed with CARBENDAZIM (‘Sportak Alpha’) it is useful e.g. against eyespot, sharp eyespot, septoria and other CEREAL DISEASES. 612

promoter progressive pneumonia virus See LENTIVIRINAE. proguanil See CHLORGUANIDE. prohead A DNA-free phage head precursor formed during bacteriophage assembly. (See e.g. BACTERIOPHAGE T4; see also SCAFFOLDING PROTEIN.) prohormone See PHEROMONE. prokaryote (procaryote) A type of CELLULAR (sense 2 or 3) MICROORGANISM in which the CHROMOSOME(s) are not separated from the cytoplasm by a specialized membrane; the CYTOPLASMIC MEMBRANE is typically devoid of sterols; chloroplasts and mitochondria are absent (cf. INTRACYTOPLASMIC MEMBRANES); RIBOSOMES have a sedimentation coefficient of ca. 70S; a CELL WALL is typically present and may contain structural components such as PEPTIDOGLYCAN or PSEUDOMUREIN, or may consist e.g. of an S LAYER; storage compounds may include e.g. POLYb-HYDROXYBUTYRATE; flagella (when present) are structurally relatively simple (see FLAGELLUM (a) and (c)). CHEMOLITHOAUTOTROPHS, and the ability to carry out NITROGEN FIXATION, occur only among the prokaryotes. The prokaryotes comprise two DOMAINS: the domain ARCHAEA (formerly referred to as the kingdom Archaebacteria) and the domain BACTERIA [JB (1994) 176 1–6]. Members of the two domains differ in their 16S rRNA and e.g. in the composition, structure and/or mode of assembly of the cytoplasmic membrane, cell wall and flagella; differences also occur e.g. in the composition of the ribosomal proteins. According to one hypothesis, EUKARYOTES arose from an energy-based symbiotic relationship between cells from the two prokaryotic domains [Nature (1998) 392 37–41]. prolamellar body In an ETIOPLAST: a paracrystalline array of tubules bearing a small lamellar structure (prothylakoid ) which contains certain thylakoid components (e.g. the CF1 unit of PROTON ATPASE); on illumination, prolamellar bodies disperse, and prothylakoids eventually develop into THYLAKOIDS. prolate Of a phage head: having a shape in which the distance from one pole to the other is greater than the diameter at the mid-point of the head; an example of a prolate head occurs in BACTERIOPHAGE f29. proliferative kidney disease (PKD) A FISH DISEASE which can be economically important in young salmonid fish. Symptoms include exophthalmia, anaemia, abdominal swelling and kidney hypertrophy; mortality rate: 10–95%. PKD is caused by an unclassified protozoon which apparently has affinities with members of the MYXOZOA [JP (1985) 32 254–260]. Proliferobasidium See BRACHYBASIDIALES. L-proline biosynthesis See Appendix IV(a). proloculus See FORAMINIFERIDA. promastigote A form assumed by the cells of many species of the TRYPANOSOMATIDAE (q.v.) during at least certain stages of their life cycles. prometaphase See MITOSIS. Promicromonospora A genus of asporogenous bacteria (order ACTINOMYCETALES, wall type VI) which occur e.g. in soil. The organisms form a yellow fragmenting mycelium. GC%: ca. 73. Type species: P. citrea. [Book ref. 73, pp. 53–54.] promiscuous plasmids Those CONJUGATIVE PLASMIDS (sense 1) – e.g. IncP1 plasmids – which are capable of self-transmission between bacteria of a wide range of different species and genera. promitochondrion See MITOCHONDRION. promoter In a DNA strand: a nucleotide sequence which is recognized (directly or indirectly) and bound by a DNAdependent RNA POLYMERASE (RPase) during the initiation of TRANSCRIPTION. Transcription is initiated at a position (the start

Prochlorococcus marinus See PROCHLOROPHYTES. Prochloron See PROCHLOROPHYTES. Prochlorophyta See PROCHLOROPHYTES. prochlorophytes A category of unicellular prokaryotes (order Prochlorales, division Prochlorophyta) which contain eukaryotictype chlorophylls a and b (but lack phycobiliproteins) and carry out oxygenic photosynthesis. The first member identified was Prochloron didemni (formerly Synechocystis didemni ). The cells are more or less spherical, 6–25 µm in diameter, and the photosynthetic pigments are attached to THYLAKOIDS. The organisms occur as ectosymbionts on marine didemnid ascidians (sea-squirts) in tropical and subtropical coastal waters. Species identified later include Prochlorothrix hollandica and Prochlorococcus marinus. Taxonomically (in terms of genomic sequence data), the prochlorophytes have been grouped with the cyanobacteria and chloroplasts. [Photosynthetic machinery in prochlorophytes: FEMS Reviews (1994) 13 393–414.] Prochlorothrix hollandica See PROCHLOROPHYTES. prodigiosin A red, water-insoluble, ethanol-soluble tripyrrole derivative. Prodigiosin and similar pigments are produced by some species and biotypes of SERRATIA and by other bacteria (e.g. Streptomyces spp). prodromal Refers to e.g. symptom(s) which precede the main symptoms of an infectious disease (e.g. Koplik’s spots in MEASLES). prodrug The precursor form of a drug – see e.g. FAMCICLOVIR. proenzyme Syn. ZYMOGEN. professional phagocytes PHAGOCYTES (including NEUTROPHILS and MACROPHAGES) which can kill and digest microorganisms which they have ingested. profibrinolysin See FIBRINOLYSIN. profilin See ACTIN. proflavine (proflavin) See ACRIDINES. progametangium In zygomycetes: an enlarged ZYGOPHORE which differentiates into a distal gametangium and a proximal SUSPENSOR. (See also ZYGOSPORE.) progamone See PHEROMONE. progenote A (hypothetical) primitive organism; progenotes are presumed to be the phylogenetic progenitors of both prokaryotes and eukaryotes. progressive multifocal leukoencephalopathy (PML) A human demyelinating disease that occurs primarily in those with an underlying immunological dysfunction (e.g. Hodgkin’s disease, chronic lymphatic leukaemia, AIDS); multiple small areas of demyelination develop in the white matter of the brain, resulting in progressive paralysis, mental deterioration etc. – death usually occurring within 6–12 months of the first symptoms. Characteristic of PML are enlarged nuclei in the oligodendrocytes (glial cells associated with myelin formation). It is widely belived that the causal agent of PML is a POLYOMAVIRUS: the JC virus (JC D the initials of a patient who died from PML); it is also believed that some form of immunosuppression is a prerequisite for the development of the disease. Other factor(s) may be involved; for example, one in vitro study found that the Tat protein, encoded by the AIDS virus (HIV-1), could activate the late promoter of JC virus in glial cells [PNAS (1990) 87 3479–3483]. [Murine model for PML: Cell (1986) 46 13–18. Polyomaviruses and disease of the central nervous system: RMM (1998) 9 79–85.] 613

promoter control point or start site) which is commonly within the promoter sequence. The first nucleotide to be transcribed is designated C1; nucleotides downstream of this position (i.e. those in the direction of RNA elongation: 50 -to-30 with respect to the RNA) are numbered C2, C3, C4 etc., and nucleotides in the opposite (upstream) direction are numbered
1,
2,
3 etc. Bacteria have several RPase holoenzymes (differing in their SIGMA FACTORS), each one recognizing a distinct class of promoter. In Escherichia coli most transcription is carried out by Es70 ; the enzyme binds to a region of DNA extending from ca. 50 bp upstream to ca. 20 bp downstream of the start point. Comparison of the sequences of many promoters recognized by Es70 has revealed that certain short sequences are more or less conserved. Thus, a CONSENSUS SEQUENCE, TATAAT (the Pribnow box or
10 sequence), is centred ca. 10 bp upstream from the start point, and another consensus sequence, TTGACA (the
35 sequence) is centred ca. 35 bp upstream of the start point. The start point itself is usually a purine, often an adenine residue in the sequence CAT. Promoters recognized by Es70 in E. coli differ to varying extents from the theoretical ‘consensus promoter’, and may also differ from one another in functional efficiency (efficient promoters being described as ‘strong’, inefficient ones as ‘weak’). Efficiency may be affected e.g. by changes in the consensus sequences or in the transcribed region downstream of the start point. Changes at one site may be compensated for by changes at another: thus, promoters with the same efficiencies may have different base sequencies; furthermore, a (synthetic) promoter containing the theoretical consensus sequences has been found to be relatively inefficient. Bacterial promoters of other classes (recognized by different RPase holoenzymes) also typically have two short, distinctive conserved sequences upstream from the start point; however, the actual sequences vary from one class of promoter to another. For example, in Bacillus subtilis the main holoenzyme, Es43 , recognizes the same type of promoter as does the Es70 of E. coli, but Es37 (see SIGMA FACTOR) recognizes a consensus sequence AGGATTTNA (N D any nucleotide) in the
35 region and GGAATTNTTT in the
10 region; the corresponding sequences for Es29 are TTNAAA and CATATT. (The phage T4 Esgp55 recognizes a promoter which apparently lacks a
35 sequence; in promoters recognized by the EsgpntrA of e.g. Klebsiella a
35 sequence is apparently absent, but there is a consensus sequence in the
20 region.) In eukaryotes, promoters are not recognized directly by the RNA polymerases; transcription initiation factors (TIFs) first bind to a promoter to form a pre-initiation complex, and only then does an RPase bind to form an initiation complex. Promoters for RPase II generally contain a short consensus sequence, TATA(A/T)A(A/T) (the TATA box, Goldberg–Hogness box, or Hogness box ), ca. 25–30 bp upstream from the transcription start point; this appears to be the only well-conserved sequence in RPase II promoters [NAR (1986) 14 10009–10026], although other sequences upstream of the TATA box may be important sites for the action of promoter-specific TIFs [review: Nature (1985) 316 774–778]. (See also ENHANCER.) The TATA box, found in many RPase II promoters, also occurs in a minority of type III promoters. The ‘classical’ RPase III promoters occur within the associated gene, i.e. intragenically, downstream of the start point; binding of the RPase at the promoter leads to initiation of transcription at a particular distance upstream of the binding site. One factor, the TATA box-binding protein (TBP), is necessary for the formation of an initiation complex by each of the three

types of RPase (I, II and III) – regardless of whether or not their promoters include a TATA box; TBP was first identified as a DNA-binding element in complexes assembled on type II, TATA-containing promoters, but in TATA-lacking promoters TBP appears to bind not to DNA but (directly or indirectly) to a DNA-binding protein (as well as to the polymerase) in the initiation complex. [TBP (minireview): Cell (1993) 72 7–10.] promoter control See OPERON. promycelium See METABASIDIUM. Pronase (proprietary name) A mixture of endopeptidases and exopeptidases (including carboxypeptidase(s) and aminopeptidases) which has non-specific protease activity. It is obtained from Streptomyces griseus. Prontosil An early sulphonamide, first used clinically in the 1930s; its activity was due to its breakdown in vivo to sulphanilamide. It has been superceded by the more effective, less toxic modern SULPHONAMIDES. pronucleus (1) The haploid nucleus of a gamete. (2) (protozool.) See AUTOGAMY and CONJUGATION. proof-reading (mol. biol.) A system in which the accurary of a process is increased by the removal of ‘errors’ immediately after they have occurred: see e.g. DNA REPLICATION and PROTEIN SYNTHESIS. propagative viruses See CIRCULATIVE TRANSMISSION. propagule Any disseminative unit of an organism, e.g. a spore, a mycelial fragment. propamidine An aromatic DIAMIDINE used as an antiseptic; it is active mainly against asporogenous Gram-positive bacteria and certain fungi. propeller loop fermenter A LOOP FERMENTER in which a motordriven propeller promotes circulation in the column by impelling the culture vertically up (or down) the DRAFT TUBE. proper margin (excipulum proprium) (lichenol.) Non-lichenized (i.e., wholly fungal) tissue forming the excipular margin (rim) of a lichen APOTHECIUM. A proper margin is often the same colour as the hymenial disc. (cf. THALLINE MARGIN; see also LECIDEINE APOTHECIUM.) properdin A g-globulin (MWt ca. 220000) which occurs in normal serum (ca. 25 µg/ml). Properdin promotes the alternative pathway of COMPLEMENT FIXATION by stabilizing the C3 convertase (C3bBb) in the presence of specific activators of this pathway. prophage See LYSOGENY. prophage immunity See SUPERINFECTION IMMUNITY. prophase See MITOSIS and MEIOSIS. prophylaxis Measure(s) taken to prevent the occurrence of disease – e.g. DISINFECTION, IMMUNIZATION. (See also PROTECTANT.) propiconazole (1-[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan2,2-yl-methyl]-1H-1,2,4-triazole; trade names: e.g. Radar, Tilt) An agricultural AZOLE ANTIFUNGAL AGENT which has both contact and systemic action against a wide range of plant pathogenic fungi; it has both eradicant and protectant properties against e.g. cereal diseases such as eyespot, net blotch, powdery mildew, rhynchosporium, septoria, yellow and brown rusts, etc. It may be mixed with e.g. CARBENDAZIM to give a preparation with an even broader antifungal spectrum. propidium A phenanthridine trypanocidal agent and INTERCALATING AGENT (apparent unwinding angle: 26° ). b-propiolactone (BPL) A water-miscible and non-inflammable cyclic ether (b.p. 155° C) used e.g. (in vapour form) as a surface STERILANT; it has low powers of penetration, needs a high relative humidity (ca. 70%) for maximum activity, and may be poorly effective against e.g. dried spores (cf. ETHYLENE 614

prostaglandins OXIDE).

BPL acts as an ALKYLATING AGENT, substituting proteins etc with propionic acid residues. Above 25° C it is readily hydrolysed to b-hydroxypropionic acid (hydracrylic acid); under acid conditions it forms an open-chain ester-linked polymer. BPL is an irritant and may be carcinogenic. Propionibacterium A genus of Gram-positive, asporogenous, chemoorganotrophic, anaerobic bacteria which occur e.g. in dairy products (see e.g. CHEESE-MAKING) and on the human skin, and which form propionic acid as a main product in the PROPIONIC ACID FERMENTATION of hexoses or lactate. Cells: nonmotile, pleomorphic, branched or unbranched rods or coccoid forms which may exhibit a ‘Chinese letter’ arrangement in stained preparations; some form pigments. The organisms can be cultured e.g. on yeast extract-lactate-peptone media. GC%: ca. 57–67. Type species: P. freudenreichii. P. acnes (formerly Corynebacterium parvum). The organisms ferment glucose (but not maltose or sucrose), do not hydrolyse aesculin, and are indole-positive; they digest casein and liquefy gelatin. [Extracellular proteolysis: JAB (1983) 54 263–271.] Colonies older than ca. 4 days may become reddish. (See also ACNE and SKIN MICROFLORA.) [Pathogenicity: RMM (1994) 5 163–173.] [Possible association between P. acnes and sciatica: Lancet (2001) 357 2024–2025.] Other species: P. acidi-propionici; P. freudenreichii (which incorporates P. shermanii ) (see also PYROPHOSPHATE); P. jensenii (which incorporates P. peterssonii and P. raffinosaceum); P. thoenii. [Book ref. 46, pp. 1894–1902.] propionic acid fermentation A FERMENTATION (sense 1), carried out e.g. by Propionibacterium spp, Clostridium propionicum and Megasphaera elsdenii, in which e.g. glucose and/or lactate yield propionic acid and acetic acid as the main end products. Propionibacterium spp ferment glucose or lactate via succinate [Appendix III(h)]; when lactate is the substrate the reduction of (endogenous) fumarate generates proton motive force (pmf), permiting ATP synthesis by electron transport phosphorylation. (cf. FUMARATE RESPIRATION.) C. propionicum and M. elsdenii ferment lactate via a different pathway (the acrylate pathway): lactate ! lactyl-CoA ! acrylyl-CoA ! propionyl-CoA ! propionic acid. Propionigenium A genus of anaerobic, asporogenous bacteria. P. modestum converts succinate to propionate by reactions which include the decarboxylation of methylmalonyl-CoA; this decarboxylation is coupled to the outward pumping of NaC – generating a SODIUM MOTIVE FORCE which can be used for ATP synthesis by a membrane-bound ATPase [EMBO (1984) 3 1665–1670]. Propionispira A genus of Gram-negative, obligately anaerobic, asporogenous, nitrogen-fixing bacteria which occur in trees affected with WETWOOD. The cells are curved rods or long spiral filaments; peritrichously flagellate. Various compounds are fermented: e.g. galacturonate, lactate, mannitol, and a number of sugars (e.g. glucose, lactose, sucrose); propionate, CO2 and acetate are major metabolic products. GC%: ca. 37. Type species: P. arboris. [JGM (1982) 128 2771–2779.] proplastid See e.g. CHLOROPLAST. propylene glycol See ALCOHOLS. propylene oxide A water-miscible cyclic ether (b.p. 34° C) used (in vapour form) e.g. as a disinfectant for treating certain foods; on hydrolysis it yields propylene glycol. It is also used in the preparation of specimens for ELECTRON MICROSCOPY. Prorocentrum A genus of ‘primitive’ DINOFLAGELLATES in which the cell is flattened, lacks a girdle and sulcus, and is divided longitudinally into two halves, each half containing a relatively thick, convex thecal plate. The two flagella are inserted apically.

Prorodon A genus of freshwater and marine carnivorous ciliates (subclass GYMNOSTOMATIA). Cells: ovoid, up to ca. 200 µm in length, with uniform somatic ciliature, an apical cytostome, and a cytopharynx with associated nematodesmata. Encystment is promoted e.g. by desiccation. prosenchyma See PLECTENCHYMA. prosome A stable ribonucleoprotein particle (ca. 19S) present in the nucleus and cytoplasm of various types of eukaryotic cell. Prosomes are believed to be involved in the post-transcriptional regulation of gene expression. [Prosomes – ubiquity and interspecies variation: JMB (1986) 187 479–493.] prosoplectenchyma See PLECTENCHYMA. prostacyclin (PGI2 ) A potent vasodilator, derived from PROSTAGLANDIN PGH2 , which degrades spontaneously (in minutes) to 6-oxo-PGF1a ; PGI2 promotes vascular permeability and induces pain. 6-Oxo-PGF1a levels are raised in exudates from chronic granulomas. prostaglandins (PGs) Compounds formed from ARACHIDONIC ACID via the activity of cyclo-oxygenase; this enzyme, which exists in two isoforms (COX-1 and COX-2), catalyses a twostep reaction in which the central region of the linear arachidonic acid molecule undergoes oxidative cyclization to form PGH2 , a precursor of PGF2a , PGD2 , PGE2 , PGI2 and thromboxane. Prostaglandins are included within the category eicosanoids. Cyclo-oxygenases are inhibited e.g. by compounds designated non-steroidal anti-inflammatory drugs (NSAIDs). Many of these drugs can block the activity of both COX-1 and COX-2 by binding to the enzyme in the region of an arginine residue at position 120. (The common drug aspirin (acetylsalicylic acid) – made synthetically, but also found naturally in the willow (Salix spp) – inhibits cyclo-oxygenase by acetylating a serine residue in the enzyme: Ser-530 in the COX-1 isoform, Ser-516 in COX-2.) Some NSAIDs (e.g. the tri-cyclic coxibs celecoxib and rofecoxib) specifically inhibit COX-2, such inhibition apparently involving the region near a valine residue at position 523 (isoleucine occupies 523 in COX-1); such specific inhibitors of COX-2 may be useful e.g. against certain types of cancer. Cyclo-oxygenase is apparently activated in vitro by NITRIC OXIDE [PNAS (1993) 90 7240–7244]. COX-2 is inducible (e.g. by ENDOTOXIN, immune complexes, certain CYTOKINES – e.g. INTERLEUKIN-1 and TNF-a (although expression is inhibited by IL-4 and IL-10) – and phorbol esters). COX-1 is typically produced constitutively and seems to have a ‘housekeeping’ function. (It is generally thought that NSAIDs work by inhibiting COX-2 at sites of inflammation, and that their adverse gastrointestinal effects result from inhibition of COX-1.) Particular PGs tend to be synthesized by particular types of cell. PGD2 is formed e.g. by mast cells, PGE2 and PGF2a by macrophages and monocytes, and PGI2 by endothelial cells. Following synthesis, prostaglandins may exit the cell and then act on cell-surface receptors in an autocrine or paracrine fashion; for example, PGE2 may promote an increase in the concentration of cAMP (cyclic AMP) by binding to the EP1 or EP4 receptor. Receptors for prostaglandins also occur in the cell nucleus – the so-called peroxisome proliferator-activated receptor (PPAR). Prostaglandins have many physiological roles/effects – including vasodilation (e.g. PGE2 ), vasoconstriction (e.g. PGF2a ) and the febrile response. Prostaglandins, which occur e.g. in inflammatory exudates (see also INFLAMMATION), are associated with both inflammatory and anti-inflammatory activities. Prostaglandins have other roles e.g. in kidney function and certain aspects of reproduction. 615

prostheca (See also PROSTACYCLIN.) prostheca In certain bacteria (PROSTHECATE BACTERIA): a narrow extension of the cell, bounded by the cell wall and cytoplasmic membrane; a cell may have one or more prosthecae – which may be long and narrow (e.g. in Ancalomicrobium) or short and conical (in Prosthecomicrobium), unbranched or branched. (A long, narrow prostheca is sometimes called a hypha.) In some genera prosthecae are involved in reproduction (see e.g. RHODOMICROBIUM); in Caulobacter the prostheca functions in ADHESION. (cf. STALK.) prosthecate bacteria Those bacteria which form one or more prosthecae during at least some stage of their life cycle. Genera in which the prostheca appears to have an essential reproductive role include HYPHOMICROBIUM, RHODOMICROBIUM, and some species of RHODOPSEUDOMONAS. See also ANCALOMICROBIUM, ASTICCACAULIS, CAULOBACTER, HYPHOMONAS, PEDOMICROBIUM, PROSTHECOMICROBIUM and STELLA. Prosthecochloris See CHLOROBIACEAE and CHLOROBIINEAE. Prosthecomicrobium A genus of chemoorganotrophic, strictly aerobic PROSTHECATE BACTERIA found in natural waters. The cells are coccoid, ca. 1 µm, each bearing ca. 10–30 conicallyshaped prosthecae. P. pneumaticum (type species) is nonmotile and contains GAS VACUOLES; P. enhydrum is monotrichously flagellated and lacks gas vacuoles. P. hirschii is motile (monotrichously flagellated), lacks gas vacuoles, and forms short and/or long (Ancalomicrobium-like) prosthecae [IJSB (1984) 34 304–308]. Cell division apparently occurs by budding [ibid.]. prosthetic group In an enzyme: any low-MWt, non-protein component which is firmly bound to the APOENZYME and which is necessary for the activity of the enzyme. (cf. COENZYME sense 1.) protamines Low-MWt, strongly basic proteins found e.g. in association with DNA in the sperm of fish and birds. (See also PARACOAGULATION.) Protargin See SILVER. Protargol A silver proteinate (see SILVER) used e.g. as an antiseptic and as a reagent for staining protozoan flagella. protease IV See SIGNAL HYPOTHESIS. protease inhibitors (med.) A category of ANTIRETROVIRAL AGENTS that includes the drugs amprenavir, indinavir, nelfinavir, ritonavir and saquinavir. Protease inhibitors bind to, and inhibit, the viral protease. The target enzyme, encoded by the pol region of HIV, is necessary for production of mature virions as it functions in posttranslational processing of precursor proteins. Protease inhibitors have been associated with side-effects such as lipodystrophy. proteases (peptidases) ENZYMES which hydrolyse peptide bonds in proteins and peptides. Endopeptidases cleave bonds within the peptide chain with varying degrees of specificity for particular amino acyl residues (e.g. the pancreatic enzyme trypsin hydrolyses arginyl and lysyl residues). Endopeptidases include e.g. serine proteases (characterized by a catalytically active serine residue in the active centre) and thiol proteases (in which free –SH groups occur). Serine proteases include e.g. trypsin, chymotrypsin and SUBTILISINS; they are inactivated by organic phosphate esters (e.g. diisopropylfluorophosphate, DFP) which acylate the active serine residue. Thiol proteases include e.g. BROMELAIN and PAPAIN; they are inhibited by SH-reagents such as heavy metals. Exopeptidases remove amino acids sequentially from one end of a peptide chain and include N-terminal exopeptidases (aminopeptidases) and C-terminal exopeptidases (carboxypeptidases). Proteases are termed acid, alkaline or neutral if they are active at low, high or netural pH, respectively. Microbial proteases have a number of commercial applications [Book ref. 31, pp. 49–114]. A major commercial use is

the addition of microbial proteases to domestic detergents for the digestion of proteinaceous stains in fabrics. Since most commercial detergents contain tripolyphosphate as a sequestering agent, Ca2C -requiring proteases (e.g. THERMOLYSIN) are not suitable for this purpose, and alkaline serine proteases (see SUBTILISINS) from Bacillus spp are usually used. Enzymes from Rhizomucor pusillus, R. miehei and Endothia parasitica have some use as rennin (rennet) substitutes in CHEESE-MAKING (see also CASEIN); the proteolytic-to-coagulating activity ratio of these enzymes is higher than that of rennin, and their use requires some modification of the cheese-making process in order to avoid the excessive formation of bitter peptides. Microbial proteases have some application in the manufacture of leather, although chemical methods are still cheaper; alkaline proteases from alkalophilic Bacillus spp may be used with lime for de-hairing hides, and proteases from e.g. Aspergillus oryzae or Bacillus spp may be used for bating hides (a process which makes the leather softer and more elastic). Other uses include e.g. treatment of flour to adjust its gluten composition (and hence baking qualities); as a digestive aid; and in the d´ebridement of wounds (experimental) and dissolution of blood clots (see e.g. BRINASE). (See also PRONASE.) Proteases produced by certain pathogenic microorganisms may act as virulence factors (see e.g. ELASTASE). proteasome A hollow, intracellular proteolytic structure formed by the self-assembly (autocompartmentalization) of proteases and ATPases; proteolytic sites occur in the interior of the proteasome so that protein degradation can be carried out intracellularly without risk to the cell’s integrity. A narrow entrance to the proteasome’s interior restricts access to unfolded proteins. In eukaryotes, proteasomes are used for the ATP-dependent degradation of various UBIQUITIN-bound proteins. For example, the ubiquitin–proteasome pathway is reported to be essential during changes in morphology (e.g. trypomastigote ! amastigote) in Trypanosoma cruzi [Biochem. (2001) 40 1053– 1062]. Proteasomes also occur in prokaryotes – e.g. the archaeans Methanosarcina thermophila and Thermoplasma acidophilum, and the bacteria Mycobacterium tuberculosis and Rhodococcus erythropolis. [Proteasomes in prokaryotes: TIM (1999) 7 88–92.] (See also DEGRADOSOME.) protectant (prophylactic) (plant pathol.) Any chemical agent which prevents the occurrence of particular disease(s) among plants treated with that agent. (cf. ERADICANT.) protective antigens Those antigens of a pathogen which can elicit an immune response that gives protective immunity against the pathogen. protective immunity Syn. IMMUNITY (3). Proteeae A tribe of bacteria (family ENTEROBACTERIACEAE) divided (e.g. on the basis of DNA relatedness) into three genera: MORGANELLA, PROTEUS and PROVIDENCIA. All members can oxidatively deaminate a range of amino acids. Most strains are motile (but may be non-motile at temperatures >30° C), urease Cve (cf. PROVIDENCIA), lactose
ve (although some strains may contain a Lac plasmid), indole Cve (cf. PROTEUS), VP
ve, MR Cve. Acid (š gas) is produced from glucose, and a reddish-brown pigment is produced on nutrient agar containing 5% tryptophan. Species are generally resistant to bacitracin, polymyxins and erythromycin. [Book ref. 46, pp. 1204–1224.] protein 2 A PORIN of Escherichia coli. protein A (SpA) A cell wall protein (MWt ca. 42000) found in most strains of Staphylococcus aureus; it is covalently bound 616

protein secretion (and export) to the wall peptidoglycan and can be released (intact) e.g. by LYSOSTAPHIN. SpA binds to the FC PORTION of IgG1 , IgG2 and IgG4 ; one SpA molecule can bind two IgG molecules. (cf. PROTEIN G.) SpA can also bind, apparently via the Fab region, to IgE, IgA, IgM, and some IgG3 . SpA can elicit Arthus- and anaphylaxis-type reactions, histamine release from granulocytes, and complement fixation by the classical pathway. Applications. (a) SpA immobilized on e.g. sepharose can be used in affinity CHROMATOGRAPHY for IgG purification; IgGs are eluted at pH ca. 4. (IgM and IgA elute at a lower pH.) (b) SpAcontaining staphylococci can bind to specific (IgG) antibodies (via their Fc portions) and will then agglutinate on exposure to the homologous antigen (CO-AGGLUTINATION); such antibodycoated staphylococci can be used e.g. in slide co-agglutination tests for detecting and/or identifying bacteria, toxins, etc. (c) SpA may be bound to red blood cells (e.g. with glutaraldehyde) and used e.g. to detect IgG on the surface of lymphocytes (by rosette formation). (d) SpA conjugated with an enzyme (e.g. b-lactamase, horseradish peroxidase) can be used e.g. for the assay of IgG in serum. Antigen is immobilized, incubated with the serum, and any homologous antibody binding to the antigen is detected with the SpA–enzyme conjugate; the amount of SpA bound, and hence the amount of homologous IgG in the serum, is determined by an assay of the enzymic activity (e.g. PADAC hydrolysis for b-lactamase conjugates) [PTRSLB (1983) 300 399–410]. [Properties and applications of protein A: Book ref. 44, pp. 429–480.] (See also SORTASE.) protein G A cell wall protein from group G streptococci; it resembles staphylococcal PROTEIN A in binding specifically to the Fc region of an IgG molecule, but it binds a broader range of IgG subclasses. [Structure of the IgG-binding regions of protein G: EMBO (1986) 5 1567–1575.] protein i See PRIMOSOME. protein kinase An enzyme which phosphorylates particular amino acid residues in a protein. The functions of certain proteins are regulated by phosphorylation/dephosphorylation both in eukaryotic cells (see e.g. ONCOGENE) and in Escherichia coli (see e.g. TCA CYCLE (isocitrate dehydrogenase)). (See also CYCLIC AMP.) protein kinase A See CYCLIC AMP. protein n (also n′ , n′′ ) See PRIMOSOME. protein phosphatase An enzyme which removes covalently bound phosphate from a protein; protein phosphatases have important roles e.g. in the regulation of the eukaryotic CELL CYCLE – in which they complement the activity of PROTEIN KINASES. Some protein phosphatases can cleave phosphate from more than one type of amino acid residue. (See also CYCLIN.) protein priming See DNA REPLICATION (linear genomes). protein secretion (and export) (in Gram-negative bacteria) At least five major modes of protein secretion occur in Gramnegative bacteria; they have been designated types I–V (but see note on types IV and V at the end of this entry). Type I systems. Secretion by type I systems is energized by ATP hydrolysis and involves one-step translocation from cytoplasm to exterior without a free (periplasmic) intermediate; it is exemplified by secretion of a-haemolysin by the ABC EXPORTER of Escherichia coli. Type II systems. Secretion by type II systems (the general secretory pathway, GSP) requires energy from both ATP and pmf – and, in some cases, from GTP. The first stage, translocation across the cytoplasmic membrane (CM), depends on the products of genes analogous to the sec genes of E. coli (hence,

the alternative name for type II systems: the ‘sec-dependent pathway’); the products of certain sec genes form a secretory channel through the CM. Proteins secreted by the GSP are synthesized with an Nterminal signal sequence (see SIGNAL HYPOTHESIS). In one form of type II secretion, the initial phase (transport across the CM: general export pathway, GEP) begins in the cytoplasm when the secretory protein (i.e. the one being transported) binds to a chaperone protein, SecB; binding may occur during or after translation, but before folding (folding of sec-exported proteins occurs in the periplasm). SecB is targeted to a CM-linked ATPase, SecA. SecA is associated with a SecYEG protein complex (the translocon) [JB (1997) 179 5699–5704; Nature (2002) 418 662–665] which forms a secretory channel through the CM. SecB is released (to chaperone another protein), and translocation of the protein through the CM is associated with ATP hydrolysis at SecA. During, or directly after, translocation, the signal sequence is cleaved by a specific enzyme (a signal peptidase). E. coli has two distinct signal peptidases; leader peptidase (D leader peptidase I ) is functional on a wide range of proteins, while lipoprotein signal peptidase (D signal peptidase II ) acts only on certain modified proteins (e.g. BRAUN LIPOPROTEIN). (Signal peptidases may constitute a class of serine proteases mechanistically related to b-lactamases [TIBS (1992) 17 474–478].) Excised signal peptides are degraded by a signal peptide peptidase; in E. coli at least one enzyme (‘protease IV’) carries out this function. In a variant type II pathway, transport to the CM necessarily begins at an early stage in translation. One scheme for this pathway (in E. coli ) is as follows. Initially, the nascent polypeptide (with its ribosome) binds, via the N-terminal sequence, to a signal recognition particle (SRP) that consists of (i) a 4.5S RNA molecule, and (ii) a 48 kDa multifunctional protein (with GTPase activity) designated P48 (or Ffh). It is not known whether protein–SRP binding inhibits further translation on the ribosome (as occurs in eukaryotic systems); it has been suggested that, in prokaryotes, translation arrest may not be necessary, and that the SRP pathway may simply accelerate association of nascent polypeptide chains with the translocon. A free cytosolic FtsY protein binds to the complex, and the FtsY–SRP–ribosome–polypeptide entity binds transiently, via FtsY, to the CM; hydrolysis of GTP energizes dissociation of the components, and the nascent polypeptide (with its ribosome) binds at a SecYEG (or similar) translocon. [Model for the SRP pathway in E. coli: EMBO (1998) 17 2504–2512.] (Interestingly, in Escherichia coli, reduced levels of SRP lead to the induction of a heat-shock response (see HEAT-SHOCK PROTEINS); this may help to maintain viability by increasing the cell’s capacity to degrade mislocalized CM proteins [JB (2001) 183 2187–2197].) For any given nascent polypeptide, the choice of pathway – i.e. SecB–SecA or SRP – is believed to depend on the hydrophobicity of the N-terminal sequence. Among secreted proteins, the SRP pathway may be used preferentially by those (e.g. b-lactamases) which have relatively hydrophobic Nterminal sequences. However, the SRP pathway may be used mainly for targeting and elaboration of CM proteins – whose N-terminal sequences are characteristically very hydrophobic; for these proteins, this pathway may be advantageous in that completion of translation at a membrane-associated site could avoid the risk of aggregation of hydrophobic domains which may occur in the cytoplasm. In vitro studies involving replacement or modification of the signal peptide sequence indicate that 617

protein synthesis the targeting pathway of Escherichia coli pre-secretory and integral membrane proteins is specified by the hydrophobicity of the targeting signal [PNAS (2001) 98 3471–3476]. The second stage of the GSP, translocation across the OUTER MEMBRANE, depends on a number of specific secretion factors. Although the GEP occurs in E. coli, this organism apparently does not secrete proteins via the GSP, i.e. it does not carry out the second stage of the GSP. However, other species of the Enterobacteriaceae do secrete proteins via this pathway. For example, Klebsiella oxytoca secretes a lipoprotein enzyme, pullulanase (see DEBRANCHING ENZYME), whose translocation across the outer membrane requires the products of 14 pul genes. (Interestingly, if all the pul genes from K. oxytoca are expressed in E. coli, this organism can secrete pullulanase.) Again, the GSP is used by Erwinia chrysanthemi for secreting the enzymes pectinase and cellulase, secretion needing expression of the out genes. (E. coli encoding a gene for pectinase can secrete this enzyme if supplied with out genes.) The secretory systems in K. oxytoca and E. chrysanthemi are similar though not identical: K. oxytoca can synthesize – but not secrete – a pectinase encoded by a gene from E. chrysanthemi. (See also SECRETON.) Pseudomonas aeruginosa secretes an exotoxin, and the enzymes elastase and alkaline phosphatase, via a secretory system involving the xcp genes. Interestingly, XcpA is identical to the PilD protein (involved in the formation of fimbriae) and is also homologous to PulO, a protein involved in the secretion of pullulanase, and it has been suggested that, in at least some cases, the second phase of the GSP may involve a protein complex similar to the fimbrial assembly apparatus [TIG (1992) 8 317–322; see also EMBO (2000) 19 2221–2228]. Folded proteins may cross the CM via the pmf-dependent Tat system [see Microbiology (2003) 149 547–556]. Type III systems. Secretion by type III systems occurs as a onestep process via a channel/pore which crosses the cell envelope from cytoplasm to cell surface; unlike type I systems, the type III pathway may involve 20 or more distinct proteins. (See also NEEDLE COMPLEX.) Type III systems occur in certain pathogens (including pathogens of plants [JB (1997) 179 5655–5662]). (See also VIRULON.) [Type III secretory systems and pathogenicity islands (review): JMM (2001) 50 116–126.] Components of type III systems in various species exhibit homology. Moreover, some type III components exhibit homology with components of other secretory systems – e.g. components of the basal body of the (bacterial) FLAGELLUM. Proteins secreted via type III systems include an N-terminal sequence which may be targeted to the pore or channel – but which it is not cleaved. The energy requirements of these systems are unknown, but a pore-associated protein (YscN) in a type III system of Yersinia includes binding sites typical of ATPases. In some type III systems, protein secretion seems to be activated by contact with a eukaryotic cell; at least some proteins are believed to be secreted directly into the eukaryotic cytoplasm because e.g. (i) proteins of the kind secreted by type III systems typically have little or no effect on eukaryotic cells in the absence of the secreting bacterium; (ii) some secreted proteins have been detected within eukaryotic cells; and (iii) some proteins (Yops) secreted by Yersinia have been associated with specific effects within eukaryotic cells (see VIRULON). In EHEC and EPEC strains of Escherichia coli, type III systems are reported to be regulated by QUORUM SENSING (q.v.). Proteins secreted by type III systems include e.g. the IpaB protein of Shigella (which promotes APOPTOSIS in macrophages);

the EspB and EspE proteins of enteropathogenic E. coli (EPEC); and the various Yops of Yersinia [the Yersinia Yop virulon: Mol. Microbiol. (1997) 23 861–867]. [Type III secretion systems (review): TIM (1997) 5 148–156.] Type IV systems are mechanistically distinct and not fully understood; the following is an outline of a current model. In these systems the secreted protein is synthesized as part of a larger protein that consists of (i) an N-terminal signal peptide, (ii) an a domain, and (iii) a C-terminal b domain. Initially, the whole protein is translocated across the CM in a sec-dependent manner, with cleavage of the N-terminal signal peptide. To pass through the outer membrane, the b domain is believed to form a ‘b-barrel’ pore in the membrane through which the a (‘passenger’) domain is translocated. At the bacterial surface, the a domain may (i) remain attached (exposed to the environment); (ii) undergo cleavage, but remain (non-covalently) attached; (iii) undergo cleavage and release to the environment. Cleavage may be autocatalytic, or it may involve another outer membrane protein such as the SopA protease of Shigella or the OmpT protease of Escherichia coli. In a type IV system, the translated protein (i.e. N-terminal C a domain C b domain) has been termed an autotransporter. (This term has also been used by some authors to refer specifically to the b domain; other authors have used the term to refer specifically to the a domain.) Proteins transported by type IV systems include the (cellsurface-retained) IcsA protein, associated with Shigella invasiveness in dysentery; the IGA1 PROTEASES of Haemophilus influenzae, Neisseria gonorrhoeae and N. meningitidis; and the AIDA-I system of Escherichia coli. The latter system has been used for AUTODISPLAY. Type V systems. These include the mechanism by which TDNA is transferred from Agrobacterium tumefaciens to the host cell in CROWN GALL, and the secretion of pertussis toxin by Bordetella pertussis. Note on the designation of type IV and type V systems. The name ‘type IV’ secretion system has been widely used for autotransporters by a number of authors [see e.g. TIM (1998) 6 370–378; Book ref. 218 (1999), p 42; Book ref. 223 (1999), p 94]. Some authors [see Inf. Immun. (2001) 69 1231–1243] have suggested that (i) autotransporters be called type V systems, and that (ii) secretory mechanisms referred to above as type V systems be called type IV systems. In this dictionary the designation ‘type IV’ has been retained for autotransporters. protein synthesis A protein consists essentially of one or more polypeptides – a polypeptide being a chain of amino acids linked by peptide bonds (
CO.NH
). Polypeptides are folded into a three-dimensional structure that is stabilized mainly by hydrogen and/or disulphide bonds formed between amino acids in different parts of the chain; the specific three-dimensional structure of a given protein is associated with its biological role. The biosynthesis of a protein is a complex process in which the composition of the protein (i.e. the number, nature and sequence of its amino acids) is decoded from information contained in specific sequence(s) of nucleotides. In the majority of organisms (including all cells), proteins are encoded by DNA; in certain viruses, proteins are encoded by RNA. The information in nucleic acids is expressed via a GENETIC CODE (q.v.). Unlike the polymerization of nucleotides (see e.g. DNA SYNTHESIS), polypeptide chains are not synthesized by the polymerization of amino acids on a template. In fact, protein synthesis occurs in several stages. In all cases (in both prokaryotic and eukaryotic cells) the first stage is the synthesis of an RNA copy of the particular DNA 618

protein synthesis sequence that encodes the given protein (see TRANSCRIPTION); as this RNA transcript carries the genetic ‘message’ from DNA it is called messenger RNA (or, more usually, mRNA) – see MRNA. In some cases (commonly in eukaryotes, less commonly in prokaryotes) the initial transcript must be processed to remove non-coding part(s) (called introns) from the nucleotide sequence – see SPLIT GENE; the resulting (mature) mRNA is then used to guide assembly of the polypeptide chain – the stage of protein synthesis called translation. mRNAs which lack introns can be used directly for translation. (See also RNA EDITING.) Along the length of the mRNA molecule, groups of three consecutive bases each encode a particular amino acid. Each of these three-base groups is called a codon; thus, e.g. the codon UCA (uracil-cytosine-adenine) encodes the amino acid serine (see table in GENETIC CODE). Hence, the sequence of codons in mRNA encodes the sequence of amino acids in a polypeptide. For the synthesis of a polypeptide, each amino acid must first bind to a small ‘adaptor’ molecule of RNA which is specific for that amino acid and which also has a binding site (a threebase anticodon) for the appropriate codon. These RNA adaptor molecules are called transfer RNA (tRNA) – see TRNA. The binding of a given amino acid to its tRNA (i.e. the ‘charging’ of a tRNA molecule) occurs in a two-step reaction. First, the amino acid reacts with ATP in the presence of a specific aminoacyltRNA synthetase (forming an enzyme-bound aminoacyl-AMP complex); the aminoacyl group is then transferred to the 20 or 30 position of the terminal adenosine residue in the tRNA (with release of AMP and synthetase). (See also MUPIROCIN.) The synthesis of a polypeptide on mRNA (i.e. the translation process) takes place on a RIBOSOME. In prokaryotes, correct positioning of mRNA on the ribosome is facilitated by a particular sequence of nucleotides in the mRNA (the Shine–Dalgarno sequence) located ‘upstream’ of the coding region; this sequence base-pairs with part of a 16S rRNA molecule in the 30S subunit of the ribosome. Essentially, following mRNA–ribosome binding, the ribosome moves along the mRNA molecule in such a way that each codon, in turn, binds the relevant tRNA, and each successive amino acid is linked, covalently, to the previous one. The following outlines a generally accepted scenario for protein synthesis in Escherichia coli; some details of the process are still unknown. The process appears to be essentially similar in most or all other bacteria. Translation is initiated when mRNA binds to the ribosome. Each ribosome has two (adjacent) binding sites for charged tRNA molecules: the A site (D acceptor or entry site) and the P site (D peptidyl or donor site). At the start of translation, the first codon of mRNA (the initiator codon) coincides with the P site. The initiator codon is usually AUG, but is sometimes e.g. GUG, UUG or AUU. The initiator codon is recognized by a distinct initiator tRNA (tRNAi ) which is charged with methionine (Met). In E. coli there are two tRNAs specific for methionine: tRNAm and tRNAf ; only tRNAf can function as tRNAi (tRNAm being used for incorporation of Met in subsequent location(s) in the polypeptide chain). In the charged tRNAf the a-amino group of the methionyl residue is formylated (via N 10 -formyltetrahydrofolate), giving fMet-tRNAf ; hence, the first (N-terminal) amino acid to be incorporated in the polypeptide chain is N-formylmethionine. (The incorporation of N-formylmethionine as N-terminal amino acid is typical of prokaryotes – and of mitochondria and chloroplasts; in the eukaryotic cytoplasm, and in at least some archaeans, the methionine residue is not formylated, so that the N-terminal amino acid in these cases is methionine.)

Before discussing subsequent stages in protein synthesis, further consideration can be given to the initial binding of mRNA to the ribosome. In E. coli this preliminary step requires three protein initiation factors: IF-1, IF-2 and IF-3. The timing and mode of action of these factors is not yet fully understood, and there are several models for this phase of protein synthesis. According to one model: (i) mRNA binds to the (separate) 30S subunit of the ribosome; (ii) fMet-tRNAf binds to AUG at the P site on the 30S subunit before addition of the 50S subunit; (iii) IF-2 and GTP are needed for the binding of fMet-tRNAf to AUG; (iv) all three initiation factors will have been released by the time the 50S subunit has been added. During assembly of the complete 70S ribosome, the association of 30S and 50S subunits is linked to the hydrolysis of GTP; IF-2 acts as a GTPase. [Bacterial initiation factors in protein synthesis (review): Mol. Microbiol. (1998) 29 409–417.] Initiation can apparently also occur with a 70S monosome. This may happen e.g. when initiation occurs at an internal initiator codon in a polycistronic mRNA, the ribosome terminating synthesis of one polypeptide and initiating synthesis of the next without dissociating from the mRNA. Once tRNAi is bound to AUG at the P site on a 70S ribosome, the elongation process proceeds by sequential addition of amino acids according to the codons that follow AUG. Elongation beings when an aminoacyl-tRNA binds to the vacant A site – which is adjacent to the P site and coincident with the second codon; this decoding step requires GTP and the elongation factor T (EF-T; ‘transfer factor’). EF-T comprises two components: EF-Tu (D EF-1A; see also TUFA, TUFB GENES) and EF-Ts (D EF-1B). A complex consisting of these two components interacts with GTP, EF-Ts being displaced and the EF-Tu–GTP complex being involved in binding of the incoming tRNA to the A site; during this process GTP is hydrolysed, EFTu–GDP and phosphate being released. EF-Ts displaces GDP, re-forming the original complex – which can then react with GTP to repeat the cycle. The binding of an incoming tRNA to the A site is followed by transpeptidation, i.e. the formation of a peptide bond between the carboxyl group of fMeT-tRNAf and the a-amino group of the second amino acid (at the A site); transpeptidation is catalysed by the enzyme peptidyltransferase. (Peptidyltransferase is part of the 50S ribosomal subunit.) At this stage a dipeptidyl-tRNA occupies the A site. In the next stage, translocation, the ribosome moves along the mRNA by a distance equal to one codon (in the 50 -to30 direction), the tRNA at the P site being displaced in the process; the result of this movement is that the dipeptidyltRNA entity now occupies the P site – i.e. the A site is left vacant (and therefore ready to receive the third aminoacyltRNA). Translocation, which involves elongation factor EF-G, is accompanied by GTP hydrolysis (catalysed by EF-G); GTP hydrolysis may be necessary to effect detachment of EF-G from the ribosome [JMB (1986) 189 653–662]. (Release of EF-G from the ribosome is essential for continuation of elongation as EF-G and EF-Tu apparently bind to similar or identical sites.) The third aminoacyl-tRNA now enters the A site (coincident with the third codon of mRNA); transpeptidation follows, the carboxyl of the dipeptide being covalently joined to the a-amino group of the third amino acid. The cycle of events outlined above – decoding, transpeptidation, translocation – is repeated for each incoming aminoacyltRNA during elongation. The scheme described above is the two-site model for translocation. In the three-site model [MGG (1986) 204 221–228, q.v. 619

protein synthesis Signal sequences. Commonly, a protein which will form part of the cytoplasmic membrane, or pass through it, is synthesized with a special N-terminal sequence of amino acids (called a signal sequence) which facilitates passage into, or through, the membrane (see SIGNAL HYPOTHESIS). Protein folding. As mentioned earlier, polypeptide chains must be folded correctly in order to form functional, biologically active proteins. Folding of periplasmic, membrane and secreted proteins, frequently involves the formation of disulphide bonds between specific amino acid residues in the polypeptide chain. (In E. coli the cytoplasmic proteins generally do not contain disulphide bonds as structural features; in the cytoplasm, disulphide bonds are usually reduced by enzymes such as the NADPH-dependent thioredoxin system [but see EMBO (1998) 17 5543–5550].) In E. coli, disulphide bonds are catalysed in the periplasmic region by the Dsb proteins (encoded by genes dsbA and dsbB ). Mutations which affect dsb genes are pleiotropic – i.e. they have multiple effects; the reason for this is that disulphide bonds stabilize a range of different proteins (with widely differing functions) – for example, flagellar proteins, membrane proteins and various secreted proteins. In pathogens, mutations in the dsb genes may affect secreted protein virulence factors (and thus possibly reduce the virulence of the organism). Proteins containing proline residues may need peptidyl–prolyl isomerases for normal folding; several such isomerases (e.g. FkpA [function: Mol. Microbiol. (2001) 39 199–210], PpiA) are found in the periplasmic region in E. coli. At least some protein-folding enzymes appear to be synthesized under the regulation of a TWO-COMPONENT REGULATORY SYSTEM [see e.g. GD (1997) 11 1169–1182]. Transcription of the genes encoding certain protein-folding enzymes appears to involve sigma factor sE [GD (1997) 11 1183–1193]. Protein folding is facilitated by so-called molecular chaperones (D ‘chaperones’): molecules which bind to, and stabilize, nascent proteins – promoting correct folding/inhibiting incorrect folding; one or more chaperones may be involved in a given stage of folding or translocation. Chaperones may bind to proteins co-translationally [JBC (1997) 272 32715–32718] or post-translationally. (See also HEAT-SHOCK PROTEINS.) Although chaperones are typically proteins, the membrane lipid phosphatidylethanolamine acts as a chaperone for the E. coli protein LacY [EMBO (1998) 17 5255–5264]. [Disulphide bond formation (review): Mol. Microbiol. (1994) 14 199–205. Protein folding and misfolding (some concepts and themes): EMBO (1998) 17 5251–5254.] Some proteins are folded in the cytoplasm and may be exported via the Tat system [Microbiology (2003) 149 547–556]. [Protein folding (review): TIBS (2000) 25 611–618.] Peptide synthesis without ribosomes. Some very short polypeptides are synthesized by a multi-enzyme complex (rather than by ribosomes and RNA molecules). Such a process is used e.g. for the synthesis of certain antibiotics (including GRAMICIDINS and TYROCIDINS). [Non-ribosomal biosynthesis of peptide antibiotics (review): Eur. J. Bioch. (1990) 192 1–15.] Protein synthesis in eukaryotes. Some differences between prokaryotic and eukaryotic protein synthesis are listed below. Aminoacyl-tRNA synthetases occur in high-MWt multienzyme complexes [review: Bioch. J. (1986) 239 249–255]. There is apparently no equivalent to the Shine–Dalgarno sequence of prokaryotes. In the cytoplasmic proteins of eukaryotes (and at least some archaeans) the N-terminal methionine is not formylated.

for references], described for E. coli and e.g. ‘Halobacterium halobium’, tRNAs remain bound to the ribosome both before and after translocation, i.e. deacylated tRNA is not released from the P site during translocation; instead, it is transferred to a third ribosomal site (the E site) concomitantly with translocation. Release of deacylated tRNA from the E site is triggered by the entry into the A site of the next (incoming) aminoacyl-tRNA. Base-pairing between mRNA codons and tRNA anticodons is not sufficiently stable, in itself, to guarantee the degree of accuracy and efficiency needed in translation. It has been suggested that proof-reading may occur e.g. at the level of amino acid selection by aminoacyl-tRNA synthetases; when synthetase specificity is not high enough to prevent binding of the ‘wrong’ amino acid, the latter may be recognized and removed either at the aminoacyl-AMP stage (pre-transfer proof-reading) or at the aminoacyl-tRNA stage (post-transfer proof-reading) [see e.g. NAR (1986) 14 7529–7539]. Proof-reading may also occur during elongation; aminoglycosides such as STREPTOMYCIN may exert their effect on translational accuracy by interfering with this proof-reading system. The ribosome itself may provide help, and this appears to be given by the rRNA [see e.g. Nature (1994) 370 597–598]. Termination of translation (i.e. cessation of polypeptide synthesis) occurs when a specific termination codon (UAA, UAG or UGA in E. coli – see GENETIC CODE) appears at the A site. These codons are recognized by protein release factors (RFs); RF-1 recognizes UAA and UAG, while RF-2 recognizes UAA and UGA. The recognition of a termination codon by an RF is followed by hydrolysis of the ester bond between the tRNA (at the P site) and the polypeptide chain it carries – thus releasing the completed polypeptide; hydrolysis is catalysed by peptidyltransferase. A third factor, RF-3 (D ‘S protein’), may stimulate the activities of RF-1 and RF-2. Although the ‘stop’ signal is traditionally regarded as a triplet of bases (e.g. UAA), there is evidence that the base following a stop codon influences the efficiency of termination, and it may be that the actual stop signal is a four-base (or even longer) sequence [Mol. Microbiol. (1996) 21 213–219]. In E. coli the efficiency of termination at a stop codon is also influenced by the 50 (upstream) nucleotide context of the codon, the mechanism involving the C-terminal amino acid residues in the nascent polypeptide. [Translation termination and stop codon recognition (review): Microbiology (2001) 147 255–269.] As one ribosome translocates along the mRNA another can fill the vacated initiation site and start translation of another molecule of the polypeptide; thus, a given mRNA molecule may carry a number of ribosomes along its length – forming a polyribosome or polysome. (A single ribosome is sometimes called a monosome.) At some time after the start of elongation, the formyl group of formylmethionine (see earlier) – or formylmethionine itself – is excised from the polypeptide. In E. coli, formylmethionine is cleaved from about 50% of proteins; whether or not cleavage occurs in a given protein appears to depend on the identity of the penultimate N-terminal amino acid residue – the longer the side-chain on this residue the smaller the probability of cleavage of formylmethionine. When such cleavage does occur it is effected by METHIONINE AMINOPEPTIDASE (q.v.). When the formyl group (only) is cleaved, the reaction is catalysed by methionine deformylase (D peptide deformylase, PDF). (PDF is inhibited by certain derivatives of hydroxamic acid, but these compounds are unlikely to be useful as broad-spectrum antibacterial agents because (i) they were bacteriostatic in the organisms tested, and (ii) resistance develops readily [AAC (2001) 45 1058–1064].) 620

proton ATPase Initiation of synthesis of these proteins usually occurs at the AUG codon nearest the 50 end of the mRNA, and generally requires a capped mRNA (see MRNA) for maximum efficiency. At least nine initiation factors appear to be required. The eukaryotic eEF-1, equivalent to EF-G in E. coli, differs from the bacterial factor in being susceptible to ADPribosylation by DIPHTHERIA TOXIN. (In at least some members of the Archaea the corresponding factor is susceptible to diphtheria toxin [Book ref. 157, pp 379–410].) The sole eukaryotic release factor, designated eRF, requires GTP for activity and can recognize any termination codon. Antibiotics affecting protein synthesis: AMINOGLYCOSIDE ANTIBIOTICS, ANISOMYCIN, AURINTRICARBOXYLIC ACID, CHLORAMPHENICOL, CYCLOHEXIMIDE, FUSIDIC ACID, LINCOSAMIDES, MACROLIDE ANTIBIOTICS, OXAZOLIDINONES, PACTAMYCIN, POLYENE ANTIBIOTICS (b), PUROMYCIN, SPARSOMYCIN, STREPTOGRAMINS (including e.g. QUINUPRISTIN/DALFOPRISTIN), TETRACYCLINES, TIAMULIN, THIOSTREPTON, VIOMYCIN. proteinase (1) Syn. protease (see PROTEASES). (2) Syn. endopeptidase (see PROTEASES). proteinase K A non-specific PROTEASE obtained from Tritirachium album. (cf. PRONASE.) Proteobacteria A taxonomic category (D PURPLE BACTERIA, sense 2) within the domain BACTERIA defined on the basis of 16S rRNA sequences. Some constituent genera are listed below. Alpha subdivision. Anaplasma, Agrobacterium, Azospirillum, Bartonella, Beijerinckia, Brucella, Ehrlichia, Hyphomicrobium, Methylobacterium, Rickettsia, Rochalimaea, Rhodopseudomonas, Rhodospirillum, Wolbachia. Beta subdivision. Alcaligenes, Bordetella, Chromobacterium, Neisseria, Nitrosomonas, Rhodocyclus, Spirillum. Gamma subdivision. Acinetobacter, Coxiella, Erwinia, Escherichia, Haemophilus, Legionella, Methylobacter, Methylocaldum, Methylococcus, Methylomicrobium, Methylomonas, Nitrosococcus, Pseudomonas, Proteus, Vibrio. Delta and epsilon subdivisions. Bdellovibrio, Campylobacter, Desulfuromonas, Helicobacter, Myxococcus, Wolinella. proteomics (1) The study of a cell’s proteome (collectively, all the proteins that can be expressed) as an integrated whole. (2) As in (1) with genetic and other aspects. [Microbiology and Molecular biology Reviews (2002) 66 39–63.] proteose A soluble product of protein hydrolysis; proteoses are not coagulated by heat but are precipitated in saturated (NH4 )2 SO4 . proter (ciliate protozool.) The anterior of the two cells formed during HOMOTHETOGENIC binary fission. (cf. OPISTHE.) Proteromonadida An order of parasitic protozoa (class ZOOMASTIGOPHOREA). The cells have one or two pairs of flagella, without paraxial rods, and a single mitochondrion which lacks a kinetoplast; cysts are formed. Genera: e.g. Karatomorpha, Proteromonas. Proteromonas See PROTEROMONADIDA. Proteus A genus of Gram-negative bacteria of the tribe PROTEEAE. Cells: ca. 0.4–0.8 ð 1–3 µm. Most strains swarm at 37° C, typically forming characteristic concentric zones of growth on the moist surface of an agar or gelatin medium (see SWARMING and DIENES PHENOMENON). (Some strains may form a spreading, uniform film of growth.) Typical reactions: H2 S (in TSI) Cve (delayed in P. myxofaciens); gelatin is liquefied at 22° C; lipase Cve; urease Cve; mannose and sugar alcohols are not attacked. Nicotinic acid (but not pantothenic acid) is required for growth. GC%: 38–41. Type species: P. vulgaris. P. inconstans. See PROVIDENCIA. P. mirabilis. Indole
ve; maltose
ve, ODC Cve.

P. morganii. See MORGANELLA. P. myxofaciens. Indole
ve; maltose Cve; ornithine decarboxylase
ve; abundant slime produced e.g. in trypticase–soy broth. P. rettgeri. See PROVIDENCIA. P. shigelloides. See PLESIOMONAS. P. vulgaris. Indole Cve; maltose Cve; ornithine decarboxylase
ve. P. mirabilis and P. vulgaris occur e.g. in soil, polluted water, intestines of (healthy) man and animals, etc. P. mirabilis, in particular, is an important opportunist pathogen, causing nosocomial URINARY TRACT INFECTION, pneumonia, septicaemia, etc. P. myxofaciens was isolated from gypsy moth larvae (Porthetria dispar ). [Book ref. 22, pp. 491–494.] prothallus (lichenol.) (1) Syn. HYPOTHALLUS (sense 1). (2) A lichen thallus in the initial stages of development. prothylakoid See PROLAMELLAR BODY. proticins BACTERIOCINS from Proteus spp. protist A member of the PROTISTA. Protista (1) A taxon (kingdom) which includes the ALGAE, FUNGI and PROTOZOA (collectively, the eukaryotic protists), and the PROKARYOTES. (2) A KINGDOM comprising the eukaryotic protists – see (1) above. (cf. MONERA.) protoaecidium See UREDINIOMYCETES stage I. protoaecium See UREDINIOMYCETES stage I. Protococcidiorida An order of protozoa of the subclass COCCIDIASINA. Protococcus See PLEUROCOCCUS. protocooperation In a mixed population of microorganisms: an interaction between two (or more) different microorganisms in which each organism benefits from the activities of the other (e.g. each organism may produce a substance which stimulates the growth of the other), but in which the interaction is not obligatory for either organism. (See e.g. YOGHURT; cf. MUTUALISM.) protofilament See MICROTUBULES. Protogonyaulax tamarensis Syn. Gonyaulax tamarensis. protohaem See HAEM. protokaryote Archaic term for PROKARYOTE. protokerogen See KEROGEN. protomerite In a cephaline gregarine: the anterior of the two main regions of the (septate) cell (cf. DEUTOMERITE). In the late trophozoite stage the anterior part of the protomerite may bear an EPIMERITE. protometer In a cell: a hypothetical sensor which can respond to changes in proton motive force. protomite See TOMITE. Protomonas A genus of methylotrophic bacteria; the organisms have been re-classified in the genus Methylobacterium [IJSB (1985) 35 209]. proton ATPase (proton-translocating ATPase; HC -ATPase) Any ATPASE which can couple ATP hydrolysis to the energydependent translocation of protons across an ENERGYTRANSDUCING MEMBRANE (see CHEMIOSMOSIS) and/or which can catalyse the pmf-dependent phosphorylation of ADP to ATP. (cf. PROTON PPASE.) The most-studied HC -ATPases are the (F0 F1 )-type HC ATPases (also referred to as (F1 F0 )-type HC -ATPases) which occur e.g. in the bacterial cytoplasmic membrane, in the mitochondrial (inner) membrane, and in the thylakoid membranes of chloroplasts; these enzymes have a MWt of ca. 500000. Bacterial (F0 F1 )-type HC -ATPases consist of two distinct parts: (a) the 621

proton circuit F0 moiety, a hydrophobic protein (typically containing three kinds of subunit – designated a, b and c in Escherichia coli ) embedded in the membrane bilayer, and (b) the F1 moiety, a hydrophilic protein (typically consisting of five kinds of subunit) which has ATPase activity, and which projects – like a knob on a short ‘stalk’ – from the cytoplasmic face of the membrane. (Some authors regard the projecting stalked knob as an artefact [JUR (1985) 93 138–143].) The ‘knob’ of F1 consists of two types of subunit (designated a and b), and the ‘stalk’ consists of three types of subunit (g, d and e). Mitochondrial (F0 F1 )-type HC -ATPases are essentially similar in structure but are somewhat more complex; the stalk region of the enzyme complex includes an OLIGOMYCIN-sensitivity-conferring protein (OSCP), which does not occur in bacterial or chloroplast ATPases, and a protein (called ‘inhibitor protein’, ‘I’, or ‘IF1 ’) which inhibits the hydrolysis of newly-made ATP. The mitochondrial, bacterial and chloroplast ATPases all contain, in the F0 moiety, a DCCD-binding protein which confers sensitivity to DCCD. Nomenclature of HC -ATPases. HC -ATP-ases from different sources are designated as follows: CF0 F1 (from chloroplasts); EF0 F1 (from Escherichia coli ); MF0 F1 (from mitochondria); TF0 F1 (from certain thermophilic bacteria, e.g. ‘PS3’). Individual components may be designated e.g. CF0 , EF1 , MF0 etc. The three types of subunit in TF0 may be referred to as bands 4, 6 and 8 (from the SDS–gel electrophoresis pattern). Other types of HC -ATPase include the (E1 E2 )-type enzymes which occur e.g. in the cytoplasmic membrane in certain fungi; these enzymes differ from (F0 F1 )-type ATPases e.g. in that their activity involves the formation of a phosphorylated intermediate. (See also ATPASE for a general note on the nomenclature of ATPases.) ATP synthesis and hydrolysis. HC -ATPase-catalysed ATP synthesis requires a minimum pmf of ca. 100–200 mV. During ATP synthesis protons flow through the enzyme system, passing down the proton concentration gradient; the actual route of proton flow appears to include the side-chains of particular amino acids – e.g. aspartic acid, glutamine, lysine and tyrosine. (Interestingly, it has been proposed that the proton-conducting pathway through another energy-transducing system, the purple membrane (see BACTERIORHODOPSIN), involves a similar range of amino acids.) Much or most of the energy derived from proton translocation may be used to effect the release of ATP from the tightly cohesive ATP–HC -ATPase complex – rather than to carry out the phosphorylation step itself. In one model it is proposed that protons passing through the F1 moiety cause conformational changes in the enzyme which decrease the affinity of ATP for the catalytic site. This type of model is believed to be compatible with variable HC /P ratios – the number of protons needed to cause a given conformational change (with concomitant release of ATP) being postulated to vary with the prevailing pmf. Under some conditions HC -ATPases may catalyse either the synthesis or hydrolysis of ATP in order that GATP and pmf be more or less balanced (see CHEMIOSMOSIS). However, when pmf is below a certain level, HC -ATPases are rapidly (and reversibly) inactivated; such inactivation prevents depletion of ATP e.g. under those conditions in which, for any reason, the membrane is temporarily de-energized. In chloroplasts and bacteria inactivation of HC -ATPases occurs as a result of the tight binding between ADP and the catalytic site, while in mitochondria the enzyme is inactivated by the inhibitor protein. [Regulation of HC -ATPase activity: TIBS (1986) 11 32–35.] Inhibitors of (F0 F1 )-type HC -ATPases include e.g. AUROVERTINS, CITREOVIRIDIN, DCCD, EFRAPEPTIN, OLIGOMYCIN, QUERCETIN

and tributyltin chloride; TF1 (in contrast to the F1 moieties of mesophilic bacteria) is resistant to e.g. aurovertins, efrapeptin and quercetin. [HC -ATPases, structure and function: ARB (1983) 52 801–824; HC -ATPase as an energy-converting enzyme: Book ref. 127, pp. 149–176.] proton circuit See CHEMIOSMOSIS. proton motive force See CHEMIOSMOSIS. proton PPase (HC -PPase) Proton pyrophosphatase: a membranebound enzyme or enzyme complex which couples the hydrolysis or synthesis of PYROPHOSPHATE to the energy-linked transmembrane translocation of protons; HC -PPases occur widely e.g. in mammalian and yeast mitochondria, in chloroplasts, and in certain photosynthetic bacteria. HC -PPases function in a way analogous to that of PROTON ATPASES. Thus, e.g. PPi hydrolysis by an HC -PPase can generate or augment a proton motive force (see CHEMIOSMOSIS) which can be used for energy-requiring processes such as ION TRANSPORT, reverse electron transport, and ATP synthesis (via an HC ATPase). Conversely, an HC -PPase can use pmf, directly, for the synthesis of PPi (see also OXIDATIVE PHOSPHORYLATION); such synthesis has been reported to occur e.g. in mitochondria, in the chloroplasts of the alga Acetabularia mediterranea and of the pea plant, and in the bacterium Rhodospirillum rubrum. (See also ELECTRON TRANSPORT CHAIN (figure).) proton pump Any biochemical process which promotes the energy-requiring translocation of protons across an ENERGYTRANSDUCING MEMBRANE: see e.g. ELECTRON TRANSPORT CHAIN and PROTON ATPASE. proton reducers See ANAEROBIC DIGESTION. proton-reducing acetogen See ACETOGEN. proton translocators (protonophores) IONOPHORES which effectively increase the permeability, to protons, of the lipid bilayer in biological and/or artificial membranes; such agents act as mobile carriers of (specifically) protons, and can dissipate proton motive force (see CHEMIOSMOSIS) by effectively ‘short circuiting’ the membrane. (See also UNCOUPLING AGENTS.) Proton translocators include a number of lipophilic weak organic acids which retain lipophilicity even in the deprotonated (dissociated) state (owing to delocalization of charge within the molecule); in the protonated state proton translocators deliver protons to one side of the membrane, while in the deprotonated state they accept protons from the other side. Examples include e.g. CCCP (carbonylcyanide-m-chlorophenylhydrazone), 2,4dinitrophenol, and FCCP (carbonylcyanide-p-trifluoromethoxyphenylhydrazone). protonmotive force Proton motive force (see CHEMIOSMOSIS). protonmotive Q-cycle See Q-CYCLE. protonophore Syn. PROTON TRANSLOCATOR. proto-onc See ONCOGENE. protoplasmic cylinder See SPIROCHAETALES. protoplasmodium See MYXOMYCETES. protoplast (1) The spherical or near-spherical, osmotically sensitive structure formed by the complete removal of the cell wall (e.g. by enzymic action) from a cell suspended in an isotonic (or hypertonic) medium; a protoplast thus consists of the cytoplasmic membrane and cell contents. Protoplasts can continue to metabolize – and may be able to revert to normal cells – under appropriate cultural conditions; however, protoplasts cannot divide. Bacterial protoplasts are prepared more easily from Gram-positive cells (e.g. by using LYSOZYME) than from Gram-negative cells; they are resistant to phage infection, 622

Providencia but those from previously infected cells can support phage replication. (See also SPHAEROPLAST; AUTOPLAST; L-FORM; PROTOPLAST FUSION.) (2) In an intact cell: the cytoplasmic membrane and all structures internal to it. protoplast fusion A technique for in vitro genetic transfer in which a hybrid PROTOPLAST (and ultimately a hybrid cell) is formed by fusing protoplasts derived from different strains, species or genera. Protoplasts are initially prepared e.g. by treating cells with wall-degrading enzymes (e.g. LYSOZYME for some Gram-positive bacteria); populations of two types of protoplast are then mixed. Treatment of the mixture with e.g. POLYETHYLENE GLYCOL (PEG) increases the (low) spontaneous rate of fusion. (cf. ELECTROFUSION.) The protoplasts are then transferred to an appropriate (hypertonic) solid medium for cell wall regeneration. The resulting cells can be screened for those with genetic markers from both parents; e.g., if both parents were auxotrophic (with different growth requirements) the cells can be screened for prototrophs. Hybrid bacterial protoplasts, containing a genome from each parent, are called biparentals. The two genomes may undergo recombination, or the diploids may be unstable, the two genomes segregating when the cell divides. In e.g. Bacillus subtilis, many of the progeny cells are unstable complementary diploids (i.e., genes on both genomes are expressed and can exhibit COMPLEMENTATION); however, some progeny cells are unstable non-complementing diploids (Ncd cells) in which one of the two parental genomes is expressed while the other is inactive until segregated on cell division. (cf. CONJUGATION sense 1b (ii).) (See also TRANSFORMATION.) protoplast membrane Syn. CYTOPLASMIC MEMBRANE. protoporphyrins See PORPHYRINS. Protosporangium See PROTOSTELIOMYCETES. Protostelia See EUMYCETOZOEA. protostelids See PROTOSTELIOMYCETES. Protosteliia See EUMYCETOZOEA. Protosteliomycetes (protostelids) A class of primitive slime moulds (division MYXOMYCOTA – cf. EUMYCETOZOEA) in which the vegetative phase consists of a small reticulate plasmodium or of simple amoebae which form filose – and sometimes also lobose – pseudopodia; in some species the amoebae bear one or more smooth flagella. ‘Shuttle streaming’ (i.e., rhythmic reversible flow of protoplasm) does not occur. An individual amoeba, or a segment of a plasmodium, gives rise to a fruiting body consisting of one to several spores borne on a slender tubular stalk, the whole being bounded by a sheath. Ballistospores are formed e.g. by Protostelium nocturnum [Mycol. (1984) 76 443–447], P. expulsum [TBMS (1981) 76 303–309], and Schizoplasmodium cavostelioides [sporocarp ultrastructure and development: Mycol. (1985) 77 848–860]. [Ultrastructural study of trophozoite and cyst stages of P. pyriformis: JP (1986) 33 405–411.] Protostelids are found in various habitats, including bark, rotting wood, etc. Other genera include e.g. Cavostelium, Ceratiomyxella, Endostelium [Mycol. (1984) 76 884–891], Nematostelium and Protosporangium. (cf. CERATIOMYXA.) Protostelium See PROTOSTELIOMYCETES. Prototheca A genus of unicellular eukaryotic microorganisms which are generally regarded as achlorophyllous strains of CHLORELLA. The cells are hyaline and roughly spherical or ovoid (ca. 1.3–13.4 ð 1.3–16.0 µm, depending on species, growth conditions etc); when mature, a cell divides to form 2–20 or more ‘endospores’ which are released by rupture of the mother

cell. Species occur e.g. in soil and water, and some can behave as opportunist pathogens (see PROTOTHECOSIS). protothecosis A disease, which affects man and animals, caused by a species of Prototheca (commonly P. zopfii ); typically, it involves the formation of localized skin lesions – which may be nodular, ulcerating and papular, or (rarely) granulomatous. (See also MASTITIS.) A severe, often fatal, systemic form of the disease also occurs, particularly in animals. prototroph A strain of microorganism whose nutritional requirements do not exceed those of the corresponding wild-type strain. (cf. AUXOTROPH.) prototunicate ascus An ASCUS whose wall consists of a thin, delicate membrane; the ascospores are released when the ascus wall ruptures or deliquesces. Such asci are formed e.g. by ascogenous yeasts. protoxin A precursor form of a TOXIN: see e.g. DELTA-ENDOTOXIN. protozoa A diverse group of eukaryotic, typically unicellular microorganisms; they are classified as a subkingdom (Protozoa) within the kingdom Animalia or the kingdom PROTISTA. (Some of these organisms – e.g. the SLIME MOULDS and members of the PHYTOMASTIGOPHOREA – are also classified in botanical taxonomic schemes.) The earliest known protozoa lived in the late Precambrian (see e.g. FORAMINIFERIDA). The protozoa exhibit a great variety of forms, structures and life styles, and are divided into seven phyla: APICOMPLEXA, ASCETOSPORA, CILIOPHORA, LABYRINTHOMORPHA, MICROSPORA, MYXOZOA and SARCOMASTIGOPHORA [JP (1980) 27 37–58]. Many protozoa are free-living organisms which occur in freshwater, brackish or marine habitats. Some protozoa occur e.g. in soil, some are common in SEWAGE TREATMENT plants, and some inhabit the gut in vertebrates or invertebrates (see e.g. RUMEN and TERMITE–MICROBE ASSOCIATIONS). Parasitic species include e.g. members of the Apicomplexa, Ascetospora, Microspora and Myxozoa; some protozoa are pathogenic in vertebrates (including man) or invertebrates (see e.g. BABESIA, BALANTIDIUM, EIMERIORINA, ENTAMOEBA, GIARDIA, HISTOMONAS, NAEGLERIA, NOSEMA, PLASMODIUM, TOXOPLASMA, TRYPANOSOMA). PHYTOMONAS is parasitic in certain plants. Protozoa range in size from ca. 1 µm to several millimetres; some have internal or external ‘skeletons’ of e.g. calcareous, siliceous and/or organic material. Many exhibit MOTILITY but some (see e.g. PERITRICHIA) are sedentary. Probably most protozoa are aerobic organisms, but some can grow microaerobically or anaerobically (see e.g. RUMEN and SAPROBITY SYSTEM). Feeding may occur saprotrophically and/or by pinocytosis – and/or it may occur holozoically (e.g. in many amoebae and ciliates), these organisms being classified as CARNIVOROUS, HERBIVOROUS or OMNIVOROUS. Some protozoa (see PHYTOMASTIGOPHOREA) can carry out PHOTOSYNTHESIS. Asexual reproduction may involve binary fission, multiple fission and/or budding. Sexual processes occur in some species (see e.g. AUTOGAMY and CONJUGATION). According to species, protozoa may be haploid, diploid or polyploid; some (the foraminifera) exhibit an ALTERNATION OF GENERATIONS. Populations of viable protozoa may be preserved by FREEZING (suitable e.g. for Plasmodium, Tetrahymena, Trypanosoma) or by repeated subculturing. CYST-forming species (e.g. Didinium, certain amoebae) may be encouraged to encyst (and thus survive for protracted periods) e.g. by slow desiccation or by starvation. protrichocyst Syn. EJECTOSOME. Providencia A genus of Gram-negative bacteria of the tribe PROTEEAE. Cells: ca. 0.6–0.8 ð 1.5–2.5 µm. Swarming does not occur. Species do not produce H2 S or lipase, do not 623

provirus liquefy gelatin at 22° C, and can metabolize mannose and one or more sugar alcohols; colonies on DCA typically develop yellow-orange centres due to the precipitation of Fe(OH)3 by alkaline metabolic products. Nicotinic and pantothenic acids are not required for growth. GC%: 39–42. Type species: P. alcalifaciens. P. alcalifaciens (formerly included in Proteus inconstans). Urease
ve (weak or delayed Cve in a few strains); trehalose
ve; inositol.
ve; adonitol Cve. P. rettgeri (including most of the strains formerly regarded as Proteus rettgeri ). Urease Cve; trehalose
ve; inositol Cve; adonitol Cve. P. stuartii (incorporating strains formerly included in Proteus inconstans and Proteus rettgeri ). Urease
ve (weak or delayed Cve in a few strains); trehalose Cve; inositol Cve; adonitol
ve. Providencia spp are rare in the normal human intestine, and their natural habitat is unknown. Some strains can be opportunist pathogens – P. rettgeri and P. stuartii causing e.g. nosocomial UTIs, P. alcalifaciens being more often associated with diarrhoeal illnesses. [Book ref. 22, pp. 494–496.] provirus Viral DNA which has become integrated into the chromosomal DNA of the host cell; in viruses of the RETROVIRIDAE the DNA is a transcript of the RNA genome, while in some DNA viruses the genome itself, or a portion of the genome, may integrate (see e.g. DEPENDOVIRUS, HEPATITIS B VIRUS and MASTADENOVIRUS). prozone (serol.) (1) In a titration involving antibodies and particulate antigens: absence of visible AGGLUTINATION in tubes containing the higher concentration(s) of antibody. A prozone may be due e.g. to (i) relatively low titres of BLOCKING ANTIBODIES (sense 1) which are diluted out in tubes containing agglutinating titres of normal homologous antibodies; (ii) gross ANTIBODY EXCESS; or (iii) the presence in the antiserum of substances which inhibit agglutination non-specifically. (2) In a titration involving antibodies and soluble antigens: the absence of visible precipitate in those tubes in which there is an ANTIGEN EXCESS. prozygosporangium See ZYGOSPORE. PrP 27–30 (PrP) See SCRAPIE. PrPc , PrPsc See PRION. PRRS Porcine reproductive and respiratory syndrome: see BLUEEARED PIG DISEASE. pruinose (of surfaces) Powdery in appearance. Prunus necrotic ringspot virus See ILARVIRUSES. pruritis Itching. Pruteen See SINGLE-CELL PROTEIN. Prymnesiida See PHYTOMASTIGOPHOREA. Prymnesiophyceae (Haptophyceae) A class of unicellular, uninucleate, commonly biflagellated algae (sometimes regarded as protozoa – see PHYTOMASTIGOPHOREA). Typically, the motile cell has two smooth flagella of more or less equal length, together with a HAPTONEMA; the golden-brown chloroplasts (usually two per cell) contain chlorophylls a, c1 and c2 , and fucoxanthin. Storage compounds include CHRYSOLAMINARIN. Many members can ingest food phagocytically. Most prymnesiophytes bear a covering of delicate, typically oval scales embedded in a mucilaginous matrix external to the plasmalemma; these scales are produced in the Golgi apparatus (or in vesicles probably derived therefrom) before being passed to the cell exterior (cf. CHRYSOPHYTES). The scales may be entirely organic (e.g. in Chrysochromulina and Prymnesium) or may be calcified (in certain stages of the COCCOLITHOPHORIDS). Some of the

scales may bear long or short spines, and – according to species – different types of scales may be present on the same cell and/or on different cells in different stages of the life cycle. The nature of the scales (determined by electron microscopy) is an important taxonomic characteristic. Prymnesiophytes are mostly marine organisms, forming an important component of the nannoplankton. Some species (e.g. PRYMNESIUM) occur in brackish waters, others in fresh water. Prymnesium A genus of unicellular algae (class PRYMNESIOPHYCEAE) in which the HAPTONEMA is short and immobile. Species occur in brackish water. P. parvum produces a potent, cation-activated, pH-dependent, haemolytic PHYCOTOXIN (comprising at least 6 components) which can cause mass mortalities in fish and other gill-bearing vertebrates (as well as in invertebrates) in e.g. brackish-water culture ponds. PS3 A strain of thermophilic bacteria of uncertain taxonomic affiliation. PS-5 A CARBAPENEM antibiotic. PSA fimbriae (‘PSA pili’) See FIMBRIAE. Psalliota See AGARICUS. Psammetta See XENOPHYOPHOREA. Psammina See XENOPHYOPHOREA. Psammomitra See HYPOTRICHIDA. psammophilic Preferring a sandy habitat. Psathyrella See AGARICALES (Coprinaceae). pSC101 A 9.4-kb, low-copy-number PLASMID which encodes tetracycline resistance and which has a single EcoRI cleavage site in a non-essential region, making it a useful CLONING vector. Replication of pSC101 occurs unidirectionally, does not require DNA polymerase I (cf. e.g. COLE1 PLASMID) or the host cell’s DnaA protein (see DNAA GENE) but requires a pSC101-encoded initiator protein. [Nucleotide sequence of pSC101: NAR (1984) 12 9427–9440.] PSE-type b-lactamases See b-LACTAMASES. Pseudallescheria (syn. Petriellidium) A genus of fungi of the order MICROASCALES. P. boydii (‘Allescheria boydii ’) (anamorph: Scedosporium apiospermum) occurs e.g. in soil and in faecally contaminated cattle feed. It can cause mycotic abortion e.g. in cattle; in man it is a causal agent of MADUROMYCOSIS and may be implicated in infections of the respiratory tract, sinuses etc, particularly in immunosuppressed patients. [Clinical significance of P. boydii : Mayo Clin. Proc. (1985) 60 531–537.] Pseudanabaena A genus of filamentous CYANOBACTERIA (section III) in which the trichomes are composed of cylindrical cells, with constrictions between adjacent cells; trichomes are motile and non-sheathed, and the cells contain polar GAS VACUOLES. GC%: 44–52. The genus probably includes at least some strains of ‘Oscillatoria redekei ’. pseudoaethalium See MYXOMYCETES. pseudoappendicitis See e.g. FOOD POISONING (j); see also PSEUDOTUBERCULOSIS. Pseudocaedibacter A genus of Gram-negative bacteria which occur as endosymbionts in strains of Paramecium. Cells: nonmotile rods, ca. 0.25–0.7 ð 0.5–4.0 µm, which do not contain R bodies (cf. CAEDIBACTER) and which may or may not (according to species) confer a killer characteristic on their host paramecia. GC%: ca. 35–39. Type species: P. conjugatus. P. conjugatus (see also MU PARTICLE) confers the MATE KILLER characteristic; in vitro cultivation has been reported. P. falsus (nu and pi particles) does not confer a killer characteristic. P. minutus (gamma particles) confers the killer characteristic. [Book ref. 22, pp. 807–808.] 624

Pseudomonas pseudocapillitium In the aethalia or pseudoaethalia of certain MYXOMYCETES: a system of threads (generally irregular in width) and/or of membranous or perforated plate-like structures present among the spores; it has been suggested that these structures may be remnants of sporangial walls. pseudocatalase A non-haemoprotein substance which catalyses the breakdown of H2 O2 into water and O2 ; pseudocatalases occur e.g. in various lactic acid bacteria, including strains of Lactobacillus, Enterococcus faecalis, and in some species of Veillonella. Unlike CATALASE, pseudocatalases are not inhibited by low concentrations of azide or cyanide. A manganesecontaining protein pseudocatalase (a ‘manganicatalase’) has been isolated from a strain of Lactobacillus plantarum [JBC (1983) 258 6015–6019]. Pseudocercosporella See HYPHOMYCETES; see also EYESPOT (sense 2). pseudocilia See TETRASPORA. pseudocoagulase In certain strains of Staphylococcus: any protease that mimics the effects of staphyloCOAGULASE by proteolytic activation of prothrombin, thus causing a false-positive reaction in a COAGULASE TEST. ‘Pseudocoagulase’ is believed to be a metalloprotease(s) and can be inhibited by adding EDTA to the plasma. [Book ref. 44, p. 530.] pseudocolumella In the fruiting bodies of certain MYXOMYCETES: a COLUMELLA-like, spherical or rod-shaped, calcareous structure which occurs in the centre of the sporangium; it is not attached to the peridium, but may be attached to capillitial threads. pseudocowpox A mild, usually benign CATTLE DISEASE characterized by the formation of papular, scab-forming lesions on the teats which may predispose to MASTITIS; the causal agent is a PARAPOXVIRUS. (See also MILKERS’ NODULE; cf. COWPOX.) pseudocyphella (lichenol.) A small pore (ca. 0.1–2.0 mm diam.) in the (upper and/or lower) cortex of the thallus in various lichens (e.g. species of Cetraria, Parmelia, Pseudocyphellaria). Pseudocyphellae have no definite margin (cf. CYPHELLA); they appear to be formed by the disintegration of the pseudoparenchymatous cortex, and are believed to facilitate gas exchange [Lichenol. (1981) 13 1–10]. (cf. PORED EPICORTEX.) Pseudocyphellaria A genus of foliose LICHENS (order PELTIGERALES) which closely resemble STICTA spp but differ in that the tomentose underside is perforated with PSEUDOCYPHELLAE. The upper surface may bear soredia which are yellow in P. crocata, bluish-grey in P. intricata. Species occur on soil, trees, rocks, etc. pseudocyst (protozool.) See e.g. CHAGAS’ DISEASE and TOXOPLASMOSIS. pseudoepithecium In some types of APOTHECIUM: a layer, at the surface of the hymenium, which consists of the tips of paraphyses immersed in an amorphous matrix. (cf. EPITHECIUM.) pseudo-Fiji disease See FIJI DISEASE. pseudogene In a eukaryotic chromosome: a DNA segment which resembles a known functional gene but differs in carrying deleterious mutations and in having no apparent function. Many pseudogenes resemble cDNA copies of cellular mRNAs: they have a short A–T tract at the 30 end (corresponding to the 30 poly(A) of mRNA), lack introns, and are often flanked by direct repeats; such pseudogenes are believed to have arisen by reverse transcription of cellular mRNAs. Pseudogenes have also been found in prokaryotes. For example, in Mycobacterium leprae about 27% of the genome is reported to consist of pseudogenes [Nature (2001) 409 1007–1011]. pseudoglanders Syn. EPIZOOTIC LYMPHANGITIS.

pseudohaemoptysis (pseudohemoptysis) The apparent expectoration of blood due to the coloration of sputum by red-pigmented bacteria (e.g. Serratia sp). Pseudohydnum See TREMELLALES. pseudohyphae Syn. SPROUT MYCELIUM. Pseudoklossia See EIMERIORINA. pseudolumpy skin disease See LUMPY SKIN DISEASE. pseudolysogeny A phenomenon in which an association between a BACTERIOPHAGE and its host mimics LYSOGENY in that host cell lysis is delayed or does not occur, but true lysogeny is not established. A bacterial population exhibiting pseudolysogeny can be freed of phage by prolonged incubation with neutralizing anti-phage antiserum or by serial subculture from isolated colonies. Different types of pseudolysogeny occur in different phage–bacterium systems. For example, when a population of susceptible bacteria (e.g. Shigella dysenteriae) is exposed to a virulent bacteriophage (e.g. T7) at a low multiplicity of infection, a few cells become infected. On lysis, these cells may release an enzyme which destroys the phage receptors on other cells in the population; phage virions therefore fail to adsorb to these cells – which, as a result, become (temporarily) resistant to infection (phenotypic resistance). These cells regain their susceptibility to infection after subculture in the absence of phage. In other cases the phage genome may be carried, but not expressed or replicated, within a cell in a susceptible population of bacteria, and the genome is passed to only one of the daughter cells at each cell division; a culture containing a proportion of such ‘carrier cells’ is known as a CARRIER CULTURE. After several successive transits from cell to daughter cell, the phage genome enters the lytic cycle and progeny phages are released by cell lysis. These may infect other cells which may in turn become carrier cells. This type of pseudolysogeny may occur e.g. when most of the host cells are repressed for one or more functions needed for phage replication. In Azotobacter strain O certain phages can apparently establish a pseudolysogenic state accompanied by the phenotypic conversion of the host cells (see BACTERIOPHAGE CONVERSION); the cells lose their polysaccharide capsule, become flagellated and motile, and acquire a yellow pigmented appearance [Virol. (1980) 102 267–277]. pseudomembranous colitis A severe, acute form of COLITIS. There is a profuse, watery diarrhoea, cramps, fever, and the formation of pseudomembranous patches of inflammatory exudate on the colonic mucosa (sometimes also in the small intestine). It may follow chemotherapy (e.g. with some b-LACTAM ANTIBIOTICS, clindamycin) and is linked to CLOSTRIDIUM difficile; toxins A and B kill gut epithelial cells e.g. by disrupting tight junction proteins. Inadequate IgG response may promote disease/relapse. [Review: BCG (2003) 17 475–493.] pseudomethylotroph An organism which oxidizes C1 compounds to CO2 and which assimilates C1 carbon only via the Calvin cycle. Pseudomicrothorax See HYPOSTOMATIA. Pseudomonadaceae A family of Gram-negative, aerobic, chemoorganotrophic or facultatively chemolithotrophic, typically motile (usually polarly flagellate), rod-shaped bacteria. GC%: 58–71. Genera: FRATEURIA, PSEUDOMONAS, XANTHOMONAS, ZOOGLOEA. [Book ref. 22, pp. 140–219.] Pseudomonadales A poorly defined, obsolete order of bacteria. Pseudomonas A genus of Gram-negative, aerobic, chemoorganotrophic or facultatively chemolithoautotrophic bacteria of the family PSEUDOMONADACEAE; species occur as free-living organisms in soil and aquatic habitats, and as pathogens in man, 625

Pseudomonas other animals, and plants – see e.g. BLUE PUS, BROWN BLOTCH, GINGER BLOTCH, OLIVE KNOT and TABTOXIN. [Mechanisms of plant pathogenesis: CJM (1985) 31 403–410.] (See also BUTTER and MEAT SPOILAGE.) The cells are straight or slightly curved rods, 0.5–1.0 ð 1.5–5.0 µm. In most species the majority of strains are motile with one or several unsheathed polar flagella per cell; however, sheathed flagella are formed e.g. by P. andropogonis, and some species produce both polar and lateral flagella – particularly when grown on solid media. [Biochemical and serological properties of flagella of some Pseudomonas spp: JGM (1985) 131 873–883.] Polarly fimbriate strains may exhibit TWITCHING MOTILITY. Cell walls and cytoplasmic membranes resemble those of other Gram-negative bacteria. (See also PORIN, OUTER MEMBRANE and S LAYER.) Catalase Cve; many strains are oxidase Cve. GC%: 58–70. Type species: P. aeruginosa. Nutrition, metabolism, growth. Typically, the organisms are nutritionally and metabolically highly versatile: most species will grow on inorganic salts with an organic carbon source, while some can grow chemolithoautotrophically; however, certain species (e.g. P. diminuta, P. vesicularis) require factors such as biotin, cyanocobalamin and pantothenate. Metabolism is respiratory (oxidative); many species can carry out NITRATE RESPIRATION. The TCA CYCLE operates in all species investigated. In e.g. P. aeruginosa, P. fluorescens and P. putida, glucose can be oxidized by EXTRACYTOPLASMIC OXIDATION to gluconate which may then be metabolized via the ENTNER–DOUDOROFF PATHWAY. Carbohydrates are metabolized anaerogenically. [Alternative pathways of carbohydrate metabolism in Pseudomonas: ARM (1984) 38 359–387.] HYDROCARBONS can be metabolized by some strains. Some metabolic activities are plasmid-dependent: e.g., the ability to degrade camphor, salicylate, toluate and xylene is associated with plasmids CAM, SAL, TOL and XYL, respectively. Under nitrogen-limiting conditions some species accumulate POLY-b-HYDROXYBUTYRATE. Under iron-deficient conditions, siderophores (some fluorescent) may be secreted (see NOCARDAMINE, PYOVERDIN). (See also PYOCYANIN.) Some species produce bacteriocins (see e.g. PYOCIN). In many species growth occurs optimally at ca. 28–30° C and is generally inhibited at or below ca. pH 4.5. Sensitivity to antimicrobial agents. In general, pseudomonads are resistant to a range of common antimicrobial agents; resistance may or may not be plasmid-mediated. P. aeruginosa may be sensitive to e.g. certain AMINOGLYCOSIDE ANTIBIOTICS (e.g. amikacin, gentamicin); it is resistant to many common DISINFECTANTS (cf. DETTOL CHELATE) but is usually lysed rapidly by EDTA. Susceptibility to phages. Pseudomonas spp are susceptible to a variety of phages: see e.g. BACTERIOPHAGE f6; BACTERIOPHAGE fW-14; INOVIRUS; TECTIVIRIDAE. The transducing phages F116 and G101 were used for mapping the chromosome of P. aeruginosa. Lysogeny is very common in P. aeruginosa, but is uncommon in other species. Genetic aspects. Genetic studies have often been carried out with P. aeruginosa strain PAO. [Chromosomal maps of P. aeruginosa PAO and P. putida PPN compared: JGM (1985) 131 885–896.] Gene transfer can occur by transduction and conjugation; most conjugative plasmids transfer better on solid media than in liquids [JGM (1983) 129 2545–2556]. Transformation in P. aeruginosa has been achieved with CaCl2 -treated cells. Taxonomy. A number of pseudomonads were classified by rRNA oligonucleotide cataloguing (q.v.) into rRNA

groups I
V. Group I included fluorescent species (e.g. P. aeruginosa, P. aureofaciens, P. chlororaphis, P. putida, P. syringae) and non-fluorescent species (e.g. P. alcaligenes, P. pseudoalcaligenes, P. stutzeri ), all of which (apart from some strains of P. pseudoalcaligenes) do not accumulate polyb-hydroxybutyrate (PHB). Species of groups II and III do accumulate PHB; group II included pathogens (e.g. P. cepacia, P. mallei, P. solanacearum), while group III consisted of nonpathogens (e.g. P. acidovorans, P. testosteroni ) and included some autotrophs which can grow chemolithotrophically (e.g. P. facilis, P. flava, P. paleronii and P. saccharophila). Group IV consisted of P. diminuta and P. vesicularis, while group V contained only P. maltophila; these three species require growth factors, and the last two are unable to assimilate nitrate. For group II see BURKHOLDERIA. For group V see P. maltophila, below. Many species have not been assigned to rRNA groups, and their relationship to rRNA-grouped species is uncertain; such species include e.g. P. agarici, P. amygdali, P. andropogonis, P. aurantiaca, P. avenae, P. cattleyae, P. fragi, P. fulva, P. lemoignei, P. marina (see DELEYA), P. nautica, P. spinosa and P. woodii. P. aeruginosa (formerly P. pyocyanea). Occurs in soil, river water etc, and is an important opportunist pathogen in man and other animals – being isolated from infected burns, urinary tract infections, etc. (See also BLUE PUS; EXOENZYME S; EXOTOXIN A.) It can occasionally be pathogenic in (stressed) plants. Motile strains usually have one polar flagellum per cell; rarely nonmotile. Polarly fimbriate. Colonies on nutrient agar are often roundish, flat, dull and butyrous (R-type), but can be e.g. smooth and umbonate (S-type). Mucoid (M-type) colonies are formed by ALGINATE-producing strains isolated e.g. from CYSTIC FIBROSIS patients; only some mucoid strains can produce alginate on minimal agar. Most strains produce PYOCYANIN, and may also produce e.g. PYOVERDIN, while a few strains can form a brown pigment (pyomelanin) or a red pigment (pyorubin). (Pyomelanin production is enhanced in mineral salts media containing 1% Ltyrosine; 1% DL-glutamate enhances pyorubin production.) All strains are catalase Cve and oxidase Cve; many are urease Cve. Optimum growth temperature: 37° C; all strains can grow at 42° C. GC%: ca. 67. The production of virulence factors by P. aeruginosa may be inhibited through inhibition of the organism’s QUORUM SENSING mechanisms by the macrolide antibiotic azithromycin [AAC (2001) 45 1930–1933]. P. alcaligenes. A non-fluorescent species which cannot utilize e.g. glucose, fructose, maltose or gluconate, but which can use e.g. L-arginine, malate, and propionate. Monotrichously flagellate. Growth can occur at 41° C; optimum temperature ca. 35° C. GC%: 64–68. P. andropogonis (D P. stizolobii ). A non-fluorescent, typically oxidase
ve species pathogenic e.g. for sorghum. The organisms form sheathed flagella at ca. 28° C but are nonflagellate when grown at 34° C. P. carboxydohydrogena. See CARBOXYDOBACTERIA. P. carboxydovorans. See CARBOXYDOBACTERIA. P. cepacia. A former species (see BURKHOLDERIA) found e.g. in soil, water. Oxidase Cve. Lophotrichously flagellate. Nonfluorescent pigments often formed. Opt. growth: 30–35° C. Pathogenic in man (see CYSTIC FIBROSIS) and a causal agent of soft rot in onions. P. cichorii. A fluorescent, PYOVERDIN-forming species pathogenic for chicory: Lophotrichously flagellate. Weakly oxidase Cve. Optimum growth temperature: ca. 30° C. GC%: 59. 626

pseudopodetium ‘P. cocovenenans’ (incertae sedis). See BONGKREKIC ACID. P. facilis (formerly Hydrogenomonas facilis). A nonfluorescent, non-pigmented species which occurs e.g. in soil. Monotrichously flagellate. Oxidase Cve. Glucose, fructose and malonate can be utilized; extracellular PHB is hydrolysed. The organisms can grow chemolithoautotrophically using hydrogen and oxygen (see KNALLGAS REACTION). Optimum growth temperature: ca. 28° C. GC%: 62–64. P. fluorescens. A fluorescent, PYOVERDIN-forming species which occurs e.g. in soil and water. Lophotrichously flagellate. Oxidase Cve. Gelatinase Cve. Growth can occur at 4° C but not at 41° C; optimum growth temperature: 25–30° C. GC%: ca. 59–61. (See also MUPIROCIN.) P. fragi. A psychrophilic, peritrichously fimbriate species which can cause spoilage of refrigerated foods (e.g. BUTTER). P. mallei. A non-motile, non-pigmented species which causes GLANDERS. Oxidase Cve, gelatinase Cve. D-xylose is utilized, D-ribose is not. (See BURKHOLDERIA.) P. maltophila. A former species found in e.g. soil, water and milk. Lophotrichously flagellate. Most strains need cystine or methionine; PHB is not accumulated. Strongly lipophilic. No growth at 4° C or 41° C. Re-classified initially as Xanthomonas maltophila [IJSB (1983) 33 409–413] and then as Stenotrophomonas maltophila (see CYSTIC FIBROSIS). P. marina. See DELEYA. P. nigrifaciens. See ALTEROMONAS. P. phaseolicola. See P. syringae. P. pseudoalcaligenes. A non-fluorescent species, some strains of which are pathogenic for watermelon. Monotrichously flagellate. Fructose can be utilized (cf. P. alcaligenes). GC%: 62–64. P. pseudomallei. Occurs e.g. in soil and is the causal agent of MELIOIDOSIS. Motile, lophotrichously flagellate. Oxidase Cve. Gelatinase Cve. D-Ribose can be utilized, D-xylose cannot. Yellow or orange pigments may be formed. (See BURKHOLDERIA.) P. putida. A fluorescent species which occurs e.g. in soil and water. Lophotrichously flagellate. Oxidase Cve. Optimum growth temperature: 25–30° C. Two biovars: A and B; strains of biovar B can utilize L-tryptophan and testosterone. P. putrefaciens. See ALTEROMONAS. P. pyocyanea. See P. aeruginosa. P. saccharophila. The sole strain of P. saccharophila was isolated from mud. Monotrichously flagellate. Growth can occur chemolithoautotrophically with hydrogen as electron donor. PHB is accumulated. Oxidase Cve. Optimum growth temperature: ca. 30° C. GC%: ca. 69. P. solanacearum. A plant-pathogenic species which causes wilts in e.g. members of the Solanaceae. Lophotrichously flagellate. Oxidase Cve. Some strains form brown pigments. GC%: ca. 66–68. (See BURKHOLDERIA.) P. stizolobii. See P. andropogonis. P. stutzeri. Occurs e.g. in soil and water. Non-fluorescent. PHB is not accumulated. Monotrichously flagellate, but lateral flagella are formed under certain conditions. Oxidase Cve. Starch is hydrolysed. GC%: 60–66. (See also BIOMIMETIC TECHNOLOGY.) P. syringae. A fluorescent, plant-pathogenic species. [Genetic determinants of pathogenicity in pathovar syringae: PNAS (1985) 82 406–410.] Lophotrichously flagellate. Oxidase
ve. Optimum growth temperature: ca. 25–30° C. GC%: 59–61. The species is divided into a large number of pathovars; these include (with their hosts) e.g. P. syringae pv. coronafaciens (e.g. oats); P. syringae pv. glycinea (soybean); P. syringae pv. morsprunorum (Prunus spp – see CANKER); P. syringae pv. phaseolicola (formerly P. phaseolicola) (e.g. beans); P. syringae pv.

pisi (peas); P. syringae pv. savastanoi (olive trees – see OLIVE P. syringae pv. syringae (lilac) (see also SYRINGOMYCIN); P. syringae pv. tabaci (tobacco – see TABTOXIN). P. thermocarboxydovorans. See CARBOXYDOBACTERIA. P. tolaasii. The causal agent of BROWN BLOTCH in mushrooms. [Book ref. 22, pp. 140–199; ecology, isolation, culture: Book ref. 45, pp. 655–741; the biology of Pseudomonas: Book ref. 198.] pseudomonic acid A Syn. MUPIROCIN. pseudomurein A CELL WALL polymer present in some members of the ARCHAEA (METHANOBACTERIALES); it consists of (1 ! 3)b-linked backbone chains – containing N-acetyl-D-glucosamine (and/or N-acetyl-D-galactosamine, according to species) and Nacetyl-L-talosaminuronic acid – cross-linked by peptides which contain only L-amino acids (lys, glu, ala or thr). (cf. PEPTIDOGLYCAN.) Pseudomurein is resistant to LYSOZYME and to antibiotics such as penicillins and vancomycin. [Book ref. 157. pp. 416–423.] pseudomycelium Syn. SPROUT MYCELIUM. pseudonavicella See MONOCYSTIS. pseudonigeran A water-insoluble, alkali-soluble (1 ! 3)-a-Dglucan present in the CELL WALL in certain fungi: e.g. Aspergillus nidulans, Paracoccidioides brasiliensis (yeast form), Schizophyllum commune. Pseudonigeran can act as a reserve carbohydrate for cleistothecium formation in the teleomorph of A. nidulans (Emericella nidulans). (cf. NIGERAN.) Pseudonocardia A genus of bacteria (order ACTINOMYCETALES, wall type IV) which occur e.g. in manure and soil. The organisms form non-fragmenting substrate mycelium, and unbranched aerial hyphae which give rise to chains of cylindrical spores. Mycolic acids are not formed. GC%: ca. 79. Type species: P. thermophila. [Book ref. 73, pp. 125–126; ecology, isolation, cultivation: Book ref. 46, pp. 2103–2117.] pseudoparaphysis A type of sterile, typically branched and anastomosing, usually septate filament (of unknown function) which originates in the upper wall of a pseudothecial locule and grows downwards between the asci, subsequently fusing with the lower wall. (cf. PARAPHYSIS; see also HAMATHECIUM.) pseudoparenchyma See PLECTENCHYMA. pseudoperithecium See ASCOSTROMA. Pseudoperonospora See PERONOSPORALES. pseudopilins Certain components of the SECRETON which exhibit a region of homology with the pilins of type IV fimbriae; homology is limited to the 30 (hydrophobic) amino acids found at the N-terminal of the protein, i.e. those residues which, in the pilins, interact during fimbrial assembly. Studies on those bacteria which encode both the secreton and type IV fimbriae suggested that a functional relationship may exist between the operation of the secreton and the mechanism of fimbriation. Subsequently, when genes encoding the pullulanase secreton of Klebsiella oxytoca were expressed in Escherichia coli K-12, one of the pseudopilins, PulG, was found to assemble into a pilus-like structure [EMBO (2000) 19 2221–2228]. pseudoplasmodium (1) A multicellular, commonly motile structure formed by the aggregation of amoeboid cells (prior to fruiting) in CELLULAR SLIME MOULDS. (2) The ectoplasmic net of members of the LABYRINTHULOMYCETES. (3) In the MYXOBACTERALES: a number of individual cells embedded in a slime matrix. pseudopodetium (lichenol.) A vertical, fruticose, branched or unbranched, usually solid secondary thallus which develops by growth from the primary thallus and is thus a purely thalline (vegetative, somatic) structure (cf. PODETIUM); ascocarp initials KNOT);

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pseudopodium pseudotuberculosis A self-limiting or fatal (septicaemic) disease of animals (especially rodents) due to Yersinia pseudotuberculosis; symptoms e.g.: mesenteric adenitis, chronic diarrhoea, internal caseous lesions. (Infected humans may have mesenteric adenitis or, if debilitated, septicaemia.) Wild animals form a reservoir of the pathogen. pseudotype (virol.) A virus particle which, as a result of PHENOTYPIC MIXING, contains the genome of one virus and polypeptide(s) encoded by another virus; e.g., the genome of a replication-defective virus may be encapsidated by proteins encoded by a replication-competent helper virus. pseudotyping (genetic engineering) A technique in which e.g. the envelope proteins of a retrovirus are replaced by the G glycoprotein of vesicular stomatitis virus; the pseudotyping of retroviruses enables them to infect a wider range of types of cell. [Example of use (in gene therapy): PNAS (1999) 96 10379–10384.] Some viruses used for gene delivery (in GENE THERAPY) have the disadvantage that they infect too many types of cell. Thus, if a gene is to be delivered to a specific type of cell, then viruses with a wide spectrum of target cells may have to be administered in high doses in order to allow for losses during interaction with other types of cell; such high doses of virus may expose the patient to the risk of adverse reactions. One such virus with a wide tropism is adenovirus type 5; in vitro, plasmid-mediated modification of the virion’s attachment site (pseudotyping) has been able to de-target the virus from its (widely expressed) host receptor, allowing the development of an engineered virion which is more specifically targeted [JV (2001) 75 2972–2981]. pseudovirion A ‘virion’ which contains only host-cell nucleic acid. (See e.g. TRANSDUCTION.) pseudovitellus The mycetome of an aphid. pseudo-wild phenotype See e.g. SUPPRESSOR MUTATION. y Pseudouridine (see TRNA). [PSI+ ] See PRION (sense 2). psicofuranine (9-b-D-psicofuranosyladenine) An antitumour, antimicrobial NUCLEOSIDE ANTIBIOTIC from Streptomyces hygroscopicus. It (and its close relative decoyinine) inhibits GMP synthesis by mimicking the allosteric inhibition by adenosine of XMP aminase [see Appendix V(a)]. psilocin See HALLUCINOGENIC MUSHROOMS. Psilocybe See AGARICALES (Strophariaceae) and HALLUCINOGENIC MUSHROOMS. psilocybin See HALLUCINOGENIC MUSHROOMS. Psilolechia See LECIDEA. psittacine beak and feather disease A disease of psittacines due to an ssDNA circovirus; feather, beak and immune cells are killed and the birds may die of other infections. psittacosis (parrot fever; ornithosisŁ ) An acute infectious disease which primarily affects birds – both psittacine (parrots, parakeets etc) and non-psittacine (e.g. pigeons, sparrows, canaries, domestic fowl) – but which is also transmissible to man; it is caused by Chlamydia psittaci. In birds, C. psittaci usually causes a mild or asymptomatic infection but can cause a fatal disease. The spleen and liver may be enlarged, with areas of focal necrosis; symptoms may include e.g. ocular and nasal discharge, weakness and diarrhoea. C. psittaci is present in the faeces, nasal secretions, feathers etc of infected birds. Man usually becomes infected by inhalation of dust from contaminated birds; personto-person transmission is also known. Incubation period: 4–15 days. The disease may be mild and self-limiting, resembling influenza, but it can be fatal; symptoms may include e.g. fever, cough, headache, photophobia, myalgia, and lobular pneumonitis

develop on the pseudopodetia. Pseudopodetia occur e.g. in species of PILOPHORUS and STEREOCAULON. pseudopodium An extension of an amoeboid cell formed by extrusion of the cytoplasm (bounded by the plasmalemma). Pseudopodia are characteristically formed by protozoa of the SARCODINA; according to species, pseudopodia may function in locomotion and/or in feeding, and one or more may be formed at a time by a given cell. Various types of pseudopodia are formed by sarcodines. A lobopodium (lobose pseudopodium) is blunt-ended and generally broad, and often has a clear ectoplasmic area (the hyaline cap); lobopodia may be formed eruptively, i.e., by a burst of cytoplasmic movement, or more slowly by a steady cytoplasmic flow. A filopodium (filose or filiform pseudopodium) is slender, filamentous, sometimes tapered and sometimes branched, but lacks rigid axial elements (cf. AXOPODIUM) – although it may contain microtubules. Fine, filamentous pseudopodia which branch and anastomose to form a network are called reticulopodia or rhizopodia. In some sarcodines more or less fine ‘subpseudopodia’ may arise from a broader pseudopodial lobe (see e.g. ACANTHAMOEBA). In e.g. Amoeba proteus (see AMOEBA) the lobose pseudopodia function in both feeding and locomotion. When a prey organism comes into the vicinity of a pseudopodium, the pseudopodium flows around it, initially forming a ‘cup’ (food cup) containing the prey; the plasmalemma eventually closes around the prey to form a FOOD VACUOLE. (cf. AXOPODIUM.) Locomotion in A. proteus involves the extension of pseudopodia which apparently adhere to the substratum; cytoplasm then continues to flow into one of the pseudopodia, which expands to accommodate it, and further pseudopodia are extended, etc. This type of locomotion is often regarded as typical ‘amoeboid movement’, although other forms of motility occur in other sarcodines. For example, in Pelomyxa the cell moves along by steady cytoplasmic flow without the formation of obvious pseudopodia. (See also HELIOZOEA and TAXOPODIDA.) Apart from functioning in active motility, pseudopodia in some amoebae (e.g. Vannella spp) can apparently function as flotation devices; such amoebae can, under certain conditions, produce distinct ‘flotation forms’ characterized by fine, usually hyaline pseudopodia which radiate from the central cell mass. The mechanism of pseudopodial movement is not understood. It appears to involve microfilaments of ACTIN which lie just beneath – and which interact with – the plasmalemma. pseudorabies Syn. AUJESZKY’S DISEASE. pseudoraphe See DIATOMS. pseudorinderpest Syn. PESTE DES PETITS RUMINANTS. pseudorubella Syn. EXANTHEM SUBITUM. pseudoseptum See SEPTUM (b). pseudospores See USTILAGINALES. pseudostem See PHALLALES. pseudotemperate bacteriophage A BACTERIOPHAGE which can establish PSEUDOLYSOGENY. pseudothecium See ASCOSTROMA. Pseudotrebouxia A genus of sarcinoid unicellular green algae (division CHLOROPHYTA) which occur as photobionts in many LICHENS. The cells are more or less spherical (up to ca. 30 µm in diam.). Pseudotrebouxia spp closely resemble TREBOUXIA spp except in that asexual reproduction occurs not only by the formation of zoospores and aplanospores but also by ‘vegetative cell division’, i.e., basically, the division of one cell into two non-motile vegetative cells, etc – the resulting cells remaining in contact (at least initially) to form sarciniform groupings. [Pseudotrebouxia species in lichens, and discussion of vegetative cell division: Lichenol. (1981) 13 65–86.] 628

PTS PTS (phosphoenolpyruvate-dependent phosphotransferase system) A TRANSPORT SYSTEM, found in both Gram-negative and Grampositive bacteria, in which the substrate (e.g. a hexose, disaccharide or hexitol) is phosphorylated in a reaction which is an essential part of the transport process. The source of energy (and of phosphate) is normally phosphoenolpyruvate (PEP); the formula of PEP is given in Appendix I(a). (Certain enzymes can generate PEP from ATP or GTP.) In members of the Enterobacteriaceae, sugars whose uptake is PTS-dependent (‘PTS sugars’) include glucose, fructose, mannose, mannitol, sorbitol, glucosamine, N-acetylglucosamine and N-acetylmannosamine. (cf. LACTOSE.) (Lactose is a PTS sugar e.g. in Staphylococcus aureus.) Because sugars are often metabolized via their phosphate derivatives – e.g. glucose 6-phosphate in Appendix I(a) – phosphorylation during uptake is a positive aspect of PTS transport. (Note, however, that a non-metabolizable substrate may be phosphorylated and transported by a PTS – e.g. the sugar analogue methyl a-glucoside can be transported by the glucosePTS of Escherichia coli and of Clostridium pasteurianum.) (See also STREPTOZOTOCIN.) A PTS consists of both cytoplasmic (soluble) and membranebound protein components; the early nomenclature for PTS components (enzymes I, II and III) has been somewhat modified. In the simplest case (mannitol uptake in E. coli: see diagram), PEP feeds energy and phosphate into the PTS by sequential phosphorylation of two soluble energy-coupling proteins: enzyme I (here designated I) and a histidine-containing protein, HPr (here designated H). (Genes encoding I and H occur in the same (pts) operon.) The phosphate and energy are transferred from H to a sugar-specific permease (the so-called II complex) in the cytoplasmic membrane; the permease includes a transmembrane component (IIC), involved in the binding and translocation of substrate, and two phosphorylation sites (IIA, IIB) – phosphorylation and concomitant transport (uptake) of mannitol apparently occurring only at the IIB site. Uptake of glucose by PTS (see diagram) differs in that the IIA component is soluble – adding a further cytoplasmic step to the chain of phosphorylation. Phosphorylated forms of components I and H have high free energies of hydrolysis (approximately that of PEP). The I and H components are not substrate-specific, i.e. they are required for the phosphorylation and transport of all PTS substrates; thus, mutation causing loss of one or both of these components will be pleiotropic, i.e. the mutant will be unable to transport any PTS-dependent substrate. In contrast, inactivation of a given II complex will affect the transport of only the relevant permeasespecific substrate(s). [PTS (review): Mol. Microbiol. (1994) 13 755–764.] In enterobacteria, some complex II components apparently contain oxidizable sulphhydryl groups, and it seems that only reduced forms are active [Biochem. (1985) 24 47–51]; this may indicate an energy-dependent regulation of the PTS, and may account for the observed pmf-related regulation of PTS activity. In some II complexes the components are grouped in other ways. For example, the fructose permease of enteric bacteria consists of a membrane-bound protein, containing IIC and IIB, and a separate protein containing the functions of both IIA and HPr. In Rhodobacter capsulatus, the fructose permease includes a single protein which carries out the functions of IIA, HPr and enzyme I.

with an alveolar and interstitial exudate (cf. PRIMARY ATYPICAL PNEUMONIA). Lab. diagnosis: serological tests. Chemotherapy: e.g. tetracyclines. [Review: BMB (1983) 39 163–167.] Ł Although the terms ‘psittacosis’ and ‘ornithosis’ are used by some authors as synonyms for the disease caused by C. psittaci in both psittacine and non-psittacine birds and in man, others reserve the term ‘ornithosis’ for the disease in (i) psittacine and non-psittacine birds (i.e., excluding man); (ii) non-psittacine birds and humans infected from non-psittacine birds; or (iii) nonpsittacine birds only. Psora See LECIDEA. psoralens (furocoumarins) Three-ringed heterocyclic compounds found e.g. in certain fungi and tropical fruits. A psoralen binds intercalatively (see INTERCALATING AGENT) and non-covalently to DNA or RNA in the dark. On irradiation of this complex with light (365 nm) the psoralen becomes covalently linked to a pyrimidine residue in one strand; it may then react photochemically with a second pyrimidine to form a cross-link. Owing to the small size of a psoralen molecule, two pyrimidines can be cross-linked only when they are very close (e.g. on complementary strands in a double helix or a hairpin loop). Psoralens are useful in studies on the secondary structures of DNA and RNA molecules [ARBB (1981) 10 69–86]. psoroptic mange A disease of animals caused by mite bites (see e.g. SHEEP SCAB). pst operon See PHO REGULON. PstI A RESTRICTION ENDONUCLEASE from Providencia stuartii ; CTGCA/G. PSTV Potato spindle tuber VIROID. Psychrobacter A genus of Gram type-negative bacteria formerly proposed as a member of the family Neisseriaceae [IJSB (1986) 36 388–391] but later classified within the family Moraxellaceae [IJSB (1991) 41 310–319]. Strains of P. immobilis are oxidase Cve and catalase Cve coccobacilli found e.g. in fish and processed meat products; most are psychrotrophic (optimum growth temperature: 20–25° C). GC% 44–46. psychrophile An organism which grows optimally at or below 15° C, which has an upper limit for growth of ca. 20° C, and which has a lower limit for growth of 0° C or below [Bact. Rev. (1975) 39 144–167]. (This is currently the most widely accepted definition; however, some authors still use the term, very loosely, to include PSYCHROTROPHS.) Psychrophilic organisms include certain algae and fungi, a number of Gram-negative bacteria (e.g. some species of Pseudomonas and Vibrio), and a few Grampositive bacteria (e.g. some Clostridium spp). [Ecology and physiology of psychrophilic bacteria: Book ref. 191, pp. 1–23.] (cf. MESOPHILE and THERMOPHILE.) psychrotroph An organism which can grow at low temperatures (e.g. 0–5° C) but which has an optimum growth temperature >15° C and an upper limit for growth >20° C. (cf. PSYCHROPHILE.) Psychrotrophs include e.g. certain algae and fungi, and various Gram-negative and Gram-positive bacteria. pT181 plasmids See INCOMPATIBILITY. Pterosperma See MICROMONADOPHYCEAE. pterostilbene A stilbene PHYTOALEXIN produced by the grapevine (Vitis vinifera). pteroylglutamic acid Syn. FOLIC ACID. PTFE Polytetrafluoroethylene (Teflon). PTLV Primate T-cell leukaemia virus: see SIMIAN T-CELL LEUKAEMIA VIRUS. 629

PTS regulation domain mannitol

glucose

IIC IIA P

IIC

P

CM

IIB

IIB

mannitol 1-phosphate

P

H H

I

P

IIA

glucose 6-phosphate

P

P P

PEP PTS (phosphoenolpyruvate-dependent phosphotransferase system). Transport of mannitol and glucose across the cytoplasmic membrane (CM) by the PTS in Escherichia coli (simplified, diagrammatic); transport is from the periplasm (above) to the cytoplasm (below). Note that mannitol and glucose are taken up by different membrane-associated systems (permeases). P The source of energy for transport is phosphoenolpyruvate (PEP). Energy is fed into the system by the sequential transfer of phosphate from PEP to enzyme I (shown here as I) and then to the HPr protein (shown here as H). In mannitol transport, phosphate is transferred from H direct to a membrane-bound permease (enzyme II complex, here designated II). The permease for mannitol consists of three domains: IIA, IIB and IIC. IIC is a hydrophobic, transmembrane domain which binds the specific substrate and appears to contain, or contribute to, a channel through which the substrate is translocated. The IIA and IIB domains each contain a phosphorylation site, but phosphorylation of the substrate seems directly to involve only the IIB domain. In the glucose permease, IIA is a separate (cytoplasmic, soluble) protein; however, the sequence of phosphorylation is the same as that in the mannitol permease, i.e. IIA ! IIB ! substrate. In all cases, phosphorylation of the substrate is an integral part of the transport mechanism. Reproduced from Bacteria, 5th edition, Figure 5.12, page 91, Paul Singleton (1999) copyright John Wiley & Sons Ltd, UK (ISBN 0471-98880-4) with permission from the publisher.

In the proposed nomenclature of PTS permeases [JB (1992) 174 1433–1438], the mannitol permease of E. coli is designated IICBAMtl,Eco , and the glucose permease is IICBGlc,Eco C IIAGlc,Eco (see diagram). In some cases a cell responds chemotactically to substrates taken up by a PTS (see CHEMOTAXIS). Moreover, a PTS can control some aspects of carbon utilization; thus, PTS phosphate carriers (see diagram) can regulate the activity of certain operons involved in the catabolism of carbon sources – sometimes via regulator sites designated ‘PTS regulation domains’ (PRD) [Mol. Microbiol. (1998) 28 865–874] (see CATABOLITE REPRESSION). PTS regulation domain (PRD) See CATABOLITE REPRESSION. pts operon See PTS. Ptychodiscus See RED TIDE and BREVETOXINS. Pu Purine (nucleotide). PU Palindromic unit: see REP SEQUENCE. pubescent Downy. Puccinia A genus of typically macrocylic and heteroxenous rust fungi (class UREDINIOMYCETES) which characteristically form cupulate aecia, non-peridiate uredia, and pedicellate, two-celled teliospores. Puccinia species are parasitic on a wide range of plant hosts, including monocotyledonous and dicotyledonous species. See UREDINIOMYCETES for the life cycle of P. graminis tritici. (See also BLACK STEM RUST, BROWN RUST, CHRYSANTHEMUM WHITE RUST, CROWN RUST and YELLOW RUST.) Pucciniastrum See UREDINIOMYCETES and PERIDERMIOID. puerperal fever (childbed fever; puerperal sepsis) An acute, febrile condition, following childbirth, due to infection of the uterus and/or adjacent regions – usually by streptococci but sometimes

by e.g. Clostridium spp; complications (e.g. septicaemia) may occur, and mortality rates are high in untreated cases. puerperal mastitis See MASTITIS. puerperal sepsis Syn. PUERPERAL FEVER. puffball See LYCOPERDALES and GASTEROMYCETES (Tulostomatales). puffing (mycol.) See ASCOSPORE. pul genes See PROTEIN SECRETION (type II systems). pullorum disease (bacillary white diarrhoea, BWD) An acute infectious POULTRY DISEASE caused by Salmonella pullorum; it affects mainly chicks, but also occurs e.g. in turkey poults and pheasants. Symptoms: e.g. lethargy, anorexia, white diarrhoea, weakness and neurological symptoms; lungs or joints may be affected. Mortality rates may be high. Survivors become chronic carriers: the pathogen localizes in the ovaries and infects a proportion of the eggs; chicks hatching from these eggs develop the disease, and infection can then spread to other chicks – either by ingestion of food contaminated with faeces from infected (or carrier) birds, or by inhalation of fluff from infected chicks. Lab. diagnosis: identification of S. pullorum from e.g. liver, spleen or ovaries. Carriers are detected by an agglutination test (cf. FOWL TYPHOID). Treatment: e.g. furazolidone, furaltadone. pullulan An extracellular, water-soluble, linear D-glucan synthesized by Aureobasidium (Pullularia) pullulans; it consists predominantly of MALTOTRIOSE units linked by (1 ! 6)a-glucosidic bonds. pullulanase See DEBRANCHING ENZYMES. Pullularia Syn. AUREOBASIDIUM. pullulation Asexual reproduction by BUDDING. pulmonary adenomatosis (vet.) Syn. JAAGSIEKTE. 630

putrefaction pulpwood spoilage See PAPER SPOILAGE. pulpy kidney An acute toxaemic disease of ruminants (especially lambs) caused by growth and toxigenesis by Clostridium perfringens type D in the intestines. Symptoms: diarrhoea, convulsions, paralysis, sudden death. pulque A white, viscous, acidic, alcoholic Mexican beverage made by fermenting the juices of Agave spp. The alcohol is produced by Saccharomyces cerevisiae (‘S. carbajali ’) and Zymomonas mobilis. Acidity and viscosity are contributed, respectively, primarily by Lactobacillus plantarum and dextranproducing strains of Leuconostoc. Pulque is rich in B vitamins. Tequila is made by the distillation of pulque. (See also WINEMAKING; SPIRITS.) pulse–chase technique A technique in which e.g. living cells are exposed to a pulse of labelled substrate for a fixed period of time – followed immediately by a high concentration of the unlabelled substrate (the ‘chase’ phase); the chase effectively stops further uptake/use of the labelled substrate, thus defining the duration of the pulse. The technique has been used e.g. to follow the intracellular movement of a secreted protein from the time of its synthesis to the time of secretion; for this experiment, the period of the pulse is increased in a stepwise manner. pulsed electric field (PEF) A technique involving electric fields of typically >20 kV/cm applied in pulses of up to several µs (microseconds) for the inactivation of susceptible microorganisms in a liquid medium; exposure to PEF treatment appears to bring about irreversible structural damage to the cells. In one experiment, the use of 2500 pulses of a 30 kV/cm field at 50° C reduced the level of viable cells of Mycobacterium paratuberculosis in milk by ca. 5.9 log10 cfu/ml [AEM (2001) 67 2833–2836]. This technique may have applications e.g. in the food industry. pulsed-field gel electrophoresis See PFGE. pulverulent Powdery. pulvinate Cushion-like; forming a swelling. pulvomycin See POLYENE ANTIBIOTICS (b). punctate Having surface dot(s), pore(s) etc. punctiform Dot-like. Punta Toro virus See PHLEBOVIRUS. PUO Pyrexia (fever) of unknown origin. pure culture See CULTURE. purified protein derivative See TUBERCULIN. purine nucleotide biosynthesis See NUCLEOTIDE and Appendix V(a). purity plate A plate inoculated from a given culture and subsequently incubated to determine whether the culture was pure or contaminated – the presence of two or more types of colony on the purity plate indicating a contaminated culture. puromycin (6-dimethyl-30 -deoxy-30 -p-methoxyphenylalanylamino adenosine) A NUCLEOSIDE ANTIBIOTIC obtained from Streptomyces alboniger or synthesized chemically; it is active against prokaryotes and eukaryotes. It acts primarily as an inhibitor of PROTEIN SYNTHESIS, acting as an analogue of the aminoacyl-adenyl portion of an aminoacyl-tRNA. When a peptidyl-tRNA occupies a ribosomal P site, puromycin can enter the A site and a peptide bond can be formed between the amino group of puromycin and the C-terminus of the peptide. However, puromycin does not have a hydrolysable ester bond like that linking the aminoacyl group to a tRNA, and puromycin binds only weakly to the ribosome; thus, nascent polypeptide chains (in which the C-terminus is blocked by puromycin) are released. purple bacteria (1) Bacteria of the RHODOSPIRILLINEAE. (2) A category (D PROTEOBACTERIA – q.v.) within the domain BACTERIA originally distinguished on the basis of 16S rRNA sequence

analysis [SAAM (1985) 6 143–151]. Organisms in this category are believed to have evolved from photosynthetic bacteria similar to members of the Rhodospirillineae; they are divided into the alpha, beta, gamma, delta and epsilon subdivisions. purple laver See LAVER. purple membrane In some strains of Halobacterium salinarium: functionally and structurally differentiated, purple-pigmented regions of the cytoplasmic membrane which develop under microaerobic or anaerobic conditions in the light; purple membrane may occupy up to 50% of the total membrane area – the remaining cytoplasmic membrane (which contains red carotenoid pigments) often being called the ‘red membrane’. The purple membrane utilizes light energy to effect transmembrane translocation of protons, thus generating or augmenting a proton motive force (pmf) (see CHEMIOSMOSIS); cells can therefore grow as phototrophs under anaerobic conditions (see HALOBACTERIUM). The protein component of the purple membrane consists almost entirely of BACTERIORHODOPSIN (q.v.) but includes another retinal-containing purple pigment, HALORHODOPSIN, and (in at least some cases) SLOW-CYCLING RHODOPSIN. (Strains of H. salinarium which cannot synthesize retinal may form an apoprotein-containing ‘white membrane’.) The lipids of the purple membrane are similar to those in the remainder of the cytoplasmic membrane, but they include a glycosulpholipid which is apparently unique to the purple membrane. While photocycling in bacteriorhodopsin causes an outward efflux of protons, photocycling in halorhodopsin appears to cause an inward pumping of chloride ions (rather than an outward pumping of sodium ions as was previously thought). The combined activities of light-energized bacteriorhodopsin and halorhodopsin may account for the various ion fluxes across the membrane and for the complex pattern of changes in transmembrane pH differential. When whole cells are illuminated, the steady-state or ‘resting’ membrane potential (typically ca. 100–110 mV) is increased by ca. 10–40 mV, and the ‘resting’ transmembrane pH differential (ca. 2 units at pH 5, ca. 0 units at pH 8) changes by 0–1 unit; the increased membrane potential serves to energize e.g. photophosphorylation (phosphorylation of ADP), uptake of potassium ions and efflux of sodium ions. purple non-sulphur bacteria See RHODOSPIRILLACEAE. purple sulphur bacteria See CHROMATIACEAE. purpura (med.) A condition characterized by reddish or purple patches due to haemorrhage into skin or mucous membrane and underlying tissues. A pin-point-sized haemorrhage is called a petechia, a larger one is known as an ecchymosis. purse (mycol.) See CYATHUS. purulent Containing, consisting of, or forming PUS. pus A thick, usually yellowish, fluid product of inflammation formed at the site of an infection. Pus contains proteins, leucocytes, cell fragments, and e.g. living and/or dead bacteria. (cf. BLUE PUS.) pustulan A (1 ! 6)-b-D-glucan produced by Lasallia (Umbilicaria) pustulata. pustule A small, raised, PUS-filled skin lesion. (cf. VESICLE.) pusule In many DINOFLAGELLATES: an intracellular vesicular structure which opens to the exterior via a canal and a pore; it is believed to function in osmoregulation but is apparently non-contractile (cf. CONTRACTILE VACUOLE). putidaredoxin See FERREDOXINS. putrefaction The microbial degradation of proteinaceous materials with the formation of evil-smelling products such as amines 631

putrescine cysteine-HCl, NaCl, resazurin, and glucose (added after autoclaving), and may be used as a broth (PYGB) or as an agar medium (PYGA). [Recipe: Book ref. 53, p. 1428.] Py-GLC PYROLYSIS GAS–LIQUID CHROMATOGRAPHY. pyknosis (pycnosis) (histopathol.) The shrinkage of a cell’s nucleus, resulting in the formation of a smaller, densely staining body. (cf. KARYOLYSIS; KARYORRHEXIS.) pyo- Prefix meaning pus. pyocin (pyocine; aeruginocin) Any BACTERIOCIN produced by Pseudomonas aeruginosa; pyocins are bactericidal – log-phase target cells apparently being the most sensitive. R-type pyocins (MWt ca. 107 ) resemble phage tails and are relatively insensitive to proteases; S-type pyocins (MWt ca. 105 ) are amorphous and are sensitive to proteases. Pyocin typing: see BACTERIOCIN TYPING. pyocyanin (pyocyanine) A blue-green, water-soluble and nonfluorescent phenazine pigment synthesized by Pseudomonas aeruginosa from chorismate (an intermediate in the biosynthesis of aromatic amino acids: see Appendix IV(f)); it becomes red-purple when acidified. Pyocyanin has oxygen-dependent antimicrobial activity which appears to involve the (enzymeindependent) oxidation of NADH with production of SUPEROXIDE and H2 O2 [JB (1980) 141 156–163]; it also inhibits the beating of human respiratory cilia in vitro [JCI (1987) 79 221–229]. (cf. CYANOMYCIN; see also IRON.) pyoderma Any purulent skin disease – e.g. IMPETIGO. pyofluorescein Syn. PYOVERDIN. pyogenic Able to cause formation of pus. pyomelanin See PSEUDOMONAS (P. aeruginosa). pyorubin See PSEUDOMONAS (P. aeruginosa). pyoverdin (pyoverdine; pyofluorescein; ‘fluorescein’) Any of a range of yellowish, fluorescent, water-soluble pigments produced by certain species of Pseudomonas under iron-deficient conditions; the pyoverdins act as SIDEROPHORES. A model for the iron-regulated induction of pyoverdin in P. aeruginosa proposes that, under iron-deficient conditions, the (regulatory) Fur protein dissociates from a transcriptional control site upstream of the pvdS gene, allowing synthesis of PvdS; PvdS is a sigma factor which promotes transcription of genes involved in the synthesis of pyoverdin [JB (1996) 178 2299–2313]. The pyoverdin of P. fluorescens contains a quinoline chromophore linked to a cyclic peptide; this compound represses synthesis of another siderophore, quinolobactin [AEM (2000) 66 487–492]. [Functional analysis of PvdS: JB (2000) 182 1481–1491.] PYR A substrate (N,N-dimethylaminocinnamaldehyde) which is apparently hydrolysed by all strains of Streptococcus pyogenes but by no other streptococci. In an identification test for S. pyogenes, the organisms are grown aerobically on agar plates overnight at 35° C; when PYR is added to the surface growth, colonies of S. pyogenes become red, while those of other streptococci become yellow or do not change colour. PYR is also hydrolysed by strains of ENTEROCOCCUS. Pyr(6–4)Pyo See ULTRAVIOLET RADIATION. pyracarbolid (2H-3,4-dihydro-6-methylpyran-5-carboxanilide) An agricultural systemic ANTIFUNGAL AGENT which is active e.g. against various rusts, smuts, and Rhizoctonia spp. Pyramimonas See MICROMONADOPHYCEAE. pyrazinamide 1,4-Diazine carboxamide: a drug active against Mycobacterium tuberculosis in vivo (including cells within phagosomes) and (at e.g. pH 5.6) in vitro. M. bovis is not susceptible.

(e.g. cadaverine and putrescine formed by the decarboxylation of lysine and ornithine, respectively) and HYDROGEN SULPHIDE (from sulphur-containing amino acids). Putrefaction is typically an anaerobic process and may be carried out e.g. by proteolytic clostridia; however, certain pseudomonads can bring about the aerobic putrefaction of e.g. meat. putrescine See POLYAMINES, DECARBOXYLASE TESTS and PUTREFACTION. Puumala virus See HANTAVIRUS. pv. Pathovar: see VARIETY. PVA See POLYVINYL ALCOHOL FIXATIVE. pvdS gene See PYOVERDIN. PVP–iodine See IODINE (a). PvuI See RESTRICTION ENDONUCLEASE (table). PWM POKEWEED MITOGEN. Py Pyrimidine (nucleotide). pyaemia (pyemia) A particular form of SEPTICAEMIA in which pyogenic bacteria are disseminated via the bloodstream. pycnidiospore A CONIDIUM formed in a PYCNIDIUM. pycnidium A hollow, typically spherical, flattened, or flaskshaped fungal fruiting body (generally ca. 100–500 µm in size) within which conidia (D pycnidiospores) are produced, and which, at maturity, is – or becomes – open to the environment e.g. via one or more pores. Pycnidia, which may superficially resemble perithecia or cleistothecia, are formed by many members of the SPHAEROPSIDALES. According to species, a pycnidium may be thick-walled or thin-walled, unilocular or multilocular, black, brown or brightly coloured (e.g. orange or yellow), glabrous or setose; it may develop superficially or may be immersed – or partly immersed – within the substratum or within a fungal stroma. [Symphogenous development of pycnidia in Chaetomella acutiseta: CJB (1980) 58 1129–1137.] pycniospore A mononucleate, haploid SPERMATIUM formed in a pycnium (see UREDINIOMYCETES). pycnium See UREDINIOMYCETES stage 0. Pycnomonas A subgenus of TRYPANOSOMA within the SALIVARIA. T. (P.) suis occurs in wild and domestic pigs in parts of Africa (e.g. Zaire) and is transmitted by Glossina spp. The organisms are stout trypomastigotes, ca. 10–20 µm, in which there is a subterminal kinetoplast and a free flagellum. pycnosis Syn. PYKNOSIS. pycnospore An obsolete term for a pycnidiospore or a pycniospore. Pycnothyriales An order of fungi (class COELOMYCETES) in which the vegetative mycelium and conidiomata may be superficial or immersed in the substratum; conidiomata may be e.g. multiloculate, and in some species each is elevated on a central columnar structure. pyelitis See PYELONEPHRITIS. pyelonephritis Inflammation of the kidney (nephritis) and the renal pelvis (pyelitis). (The renal pelvis is the region at the kidney–ureter junction.) Pyelitis and/or nephritis may be caused by infection with e.g. enterobacteria (particularly strains of Escherichia coli ), staphylococci or streptococci; infection may occur either via the bloodstream or via the urethra, bladder and ureter. Symptoms usually include fever and pain in the loins, and there may be bacteraemia. (See also CYSTITIS, GLOMERULONEPHRITIS, UPEC and URINARY TRACT INFECTION.) pyemia See PYAEMIA. PYG medium Peptone–yeast extract–glucose medium, used e.g. for culture of anaerobes. It contains peptone, yeast extract, 632

Pyrrhophyta pyrimidine dimer See ULTRAVIOLET RADIATION. pyrimidine nucleotide biosynthesis See NUCLEOTIDE and Appendix V(b). pyrimine See SERRATIA. Pyrocystis See BIOLUMINESCENCE. Pyrodictium A genus of chemolithoautotrophic prokaryotes (order THERMOPROTEALES) isolated from a submarine volcanic region. Growth occurs as a network of filaments associated with ‘discs’, each ca. 0.3–2.5 µm in diameter. Optimum growth temperature: 105° C. Growth occurs in up to 12% NaCl. Pyrodinium See BIOLUMINESCENCE. pyrogen (1) A fever-inducing agent. (2) LIPOPOLYSACCHARIDE. pyrogenic exotoxin C See TOXIC SHOCK SYNDROME. pyrogram See PYROLYSIS GAS–LIQUID CHROMATOGRAPHY. pyrolysate See PYROLYSIS. pyrolysis A technique, used e.g. in microbial taxonomy, in which a small sample of a microbial culture is thermally degraded, in a vacuum or in an inert atmosphere (e.g. nitrogen), to form a range of volatile low-MWt compounds characteristic of the organism(s); the products (pyrolysate) may be analysed by e.g. Py-GLC or Py-MS (see following entries). In filament pyrolysers the sample may be coated onto a platinum filament which is then heated by the transmission of an electric current. (See also CURIE POINT PYROLYSIS.) Laser pyrolysers have also been used. pyrolysis gas–liquid chromatography (Py-GLC) An analytical technique, intended e.g. for the rapid characterization of microorganisms, in which microbial cells are subjected to PYROLYSIS and the pyrolysate components are separated by gas–liquid CHROMATOGRAPHY and recorded as a complex trace (pyrogram). pyrolysis–mass spectrometry (Py-MS) An analytical technique, intended e.g. for the rapid characterization of microorganisms, in which microbial cells are subjected to PYROLYSIS and the pyrolysate is analysed by mass spectrometry. Pyronema A genus of fungi (order PEZIZALES) which occur e.g. on burnt soils. The apothecium (commonly 1–2 mm diam.), which develops on a subiculum, may be white, pale orange or pinkish. Ascospores: uninucleate, colourless, eguttulate. pyronin A red basic xanthene DYE. pyrophosphate (inorganic pyrophosphate; PPi) Pyrophosphate (P2 O7 4
) is involved in various metabolic reactions in both prokaryotic and eukaryotic organisms. In many organisms PPi is released from nucleoside triphosphates e.g. during the biosynthesis of nucleic acids and proteins; in some organisms it is synthesized by photophosphorylation (e.g. in Rhodospirillum rubrum) or OXIDATIVE PHOSPHORYLATION (e.g. in animal and plant mitochondria) involving a PROTON PPASE. In e.g. Propionibacterium freudenreichii (formerly P. shermanii ) and Entamoeba histolytica, PPi is used for the (reversible) phosphorylation of fructose 6-phosphate catalysed by PPi:phosphofructose dikinase – a reaction which appears to be important in the glycolytic pathway in these organisms. In DESULFOTOMACULUM (q.v.) PPi is used for the SUBSTRATELEVEL PHOSPHORYLATION of ADP; sulphate-reducing bacteria which lack the enzyme acetate:PPi phosphotransferase (e.g. Desulfovibrio) cannot use PPi in this way. pyrophosphotransferase See STRINGENT CONTROL (1). Pyrosequencing A rapid method for sequencing short DNA templates based on detection of the pyrophosphate released when a series of (known) nucleotides sequentially extend a primer [principle, details: Science (1998) 281 363–365]. Pyrrhophyta Syn. PYRROPHYTA.

Pyrazinamide is a prodrug which is converted, in vivo, to the active compound pyrazinoic acid; conversion involves the enzyme pyrazinamidase, which is encoded by gene pncA in Mycobacterium tuberculosis. Most pyrazinamide-resistant clinical isolates of M. tuberculosis have been found to have mutations in the pncA gene. Expression of M. smegmatis pyrazinamidase in mutant (pyrazinamide-resistant) M. tuberculosis confers hypersensitivity to pyrazinamide and related amides [JB (2000) 182 5479–5485]. pyrazinoic acid See PYRAZINAMIDE. pyrazophos An antifungal ORGANOPHOSPHORUS COMPOUND which is active against various powdery mildews. It is readily absorbed by leaves and shoots, and is translocated within the plant; it is poorly absorbed by roots. pyrBI, pyrE genes See OPERON. pyrenoid A dense proteinaceous body which occurs within a CHLOROPLAST; in some cases a pyrenoid may be ‘stalked’ – protruding from the chloroplast but always contained by the chloroplast envelope. The pyrenoid appears to be the site of synthesis of storage polysaccharide; the enzyme RuBisCO has been isolated as the main protein component of the pyrenoids in some species. Pyrenomycetes A class of ascomycetes characterized by the formation of unitunicate asci in a perithecium or a cleistothecium. The class is not recognized in most modern taxonomic schemes. Pyrenophora See DOTHIDEALES. Pyrenula See PYRENULALES. Pyrenulales An order of saprotrophic and lichenized fungi of the ASCOMYCOTINA. Ascocarp: ascolocular and perithecioid (see ASCOCARP). Asci: bitunicate. Ascospores: multiseptate. Genera: e.g. Acrocordia, Pyrenula. Pyricularia A genus of fungi of the HYPHOMYCETES; teleomorph: Magnaporthe. P. oryzae, the causal agent of rice BLAST DISEASE, forms a septate mycelium and gives rise to typically pyriform, commonly biseptate conidia. pyricularin Syn. PIRICULARIN. pyridine haemochrome See CYTOCHROMES. pyridine nucleotide coenzymes NAD (q.v.) and NADP. pyridine nucleotide salvage cycle See NAD. pyridoxal phosphate See PYRIDOXINE. pyridoxamine See PYRIDOXINE. pyridoxine (pyridoxin; vitamin B6 ; pyridoxol) A water-soluble and photolabile VITAMIN: 2-methyl-3-hydroxy-4,5-di-(hydroxymethyl)pyrimidine; related compounds such as pyridoxal and pyridoxamine (bearing, respectively,
CHO and
CH2 NH2 at the 4-position) may also be referred to as ‘vitamin B6 ’. The coenzyme form of the vitamin is pyridoxal 5-phosphate (‘codecarboxylase’); pyridoxamine 5-phosphate is involved in some reactions. The coenzyme is important in amino acid metabolism – e.g., in reactions involving transamination, decarboxylation, racemization (interconversion of D-and L-amino acids), serine–glycine interconversion, etc. Certain microorganisms (e.g. Clostridium spp, Lactobacillus spp, some yeasts, Crithidia fasciculata, Tetrahymena spp) require an exogenous supply of pyridoxine; the various derivatives are not necessarily equally effective in this respect. pyridoxol Syn. PYRIDOXINE. pyriform Pear-shaped. pyrimethamine (2,4-diamino-5-(p-chlorophenyl)-6-ethylpyrimidine) A FOLIC ACID ANTAGONIST used – usually in combination with e.g. a sulphonamide – in the treatment of MALARIA and of toxoplasmosis and other coccidioses; it is active against the trophozoite, but resistance tends to develop readily. 633

pyrrolo-(1,4)-benzodiazepine antibiotics tube which penetrates the host plant – giving rise to both intercellular and intracellular mycelium; haustoria are not formed. Later, spherical or ovoid, non-deciduous sporangia develop, in terminal or intercalary positions, on undifferentiated sporangiophores. A sporangium germinates by extruding a thin tube which terminates in a thin-walled, bubble-like vesicle; the multinucleate contents of the sporangium flow into the vesicle where they differentiate into zoospores. In sexual reproduction, a spherical oogonium and a smaller, club-shaped or elongated antheridium develop on the hyphae in a terminal or intercalary position. (Most species of Pythium appear to be homothallic, but at least one species, P. sylvaticum, is heterothallic.) Meiosis is generally thought to occur in the gametangia. A fertilization tube develops between antheridium and oogonium, and a male nucleus passes into the oogonium where fertilization occurs. The resulting thick-walled oospore germinates to form a germ tube which may terminate in a zoosporangium. Pythium red rot See ALGAL DISEASES. Pythonella See EIMERIORINA. pyuria The presence of pus in the urine. ‘Sterile pyuria’ (D ‘abacterial pyuria’) is a condition in which pus is repeatedly found in samples of urine from which no bacteria can be cultured by routine methods; common causes are probably chlamydiae or mycoplasmas. pYV plasmid See VIRULON.

pyrrolo-(1,4)-benzodiazepine antibiotics See ANTHRAMYCIN. pyrrolo-quinoline quinone See QUINOPROTEIN. Pyrrophyta (Pyrrhophyta) A division of the algae which includes the DINOFLAGELLATES and sometimes also the CRYPTOPHYTES. Pyrsonympha See OXYMONADIDA. pyruvate An intermediate in a wide range of (aerobic and anaerobic) metabolic pathways; for examples of formation and fates of pyruvate see Appendices I, II, III and IV(b, e). pyruvate carboxylase A BIOTIN ENZYME which is an important anaplerotic enzyme (see Appendix II (b)). [Structure: FEMS Reviews (1993) 104 330–332.] pyruvate dehydrogenase complex See e.g. Appendix II(a). pyruvate synthase See TCA CYCLE and REDUCTIVE TRICARBOXYLIC ACID CYCLE. pyruvic phosphoroclasm See PHOSPHOROCLASTIC SPLIT. Pythium A genus of aquatic and terrestrial fungi (order PERONOSPORALES) which include saprotrophs, parasites, and pathogens of higher plants (see e.g. DAMPING OFF), certain algae (see ALGAL DISEASES), and mammals (see EQUINE PHYCOMYCOSIS). (See also MYCOPARASITE.) The thallus is a well-developed, branching mycelium, and sporangia are borne on sporangiophores which typically resemble somatic hyphae. The generalized life cycle of a representative species, P. debaryanum, is as follows. A reniform zoospore (flagella arising from the concave surface) encysts and later forms a germ

1. Words in SMALL CAPITALS are cross-references to separate entries. 2. Keys to journal title abbreviations and Book ref. numbers are given at the end of the Dictionary. 3. The Greek alphabet is given in Appendix VI. 4. For further information see ‘Notes for the User’ at the front of the Dictionary.

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Dictionary of Microbiology and Molecular Biology, Third Edition Paul Singleton and Diana Sainsbury © 2006 John Wiley & Sons Ltd. ISBN: 0-470-03545-5

Q Q (1) See TEMPERATURE COEFFICIENT. (2) QUEUOSINE. (3) Glutamine (see AMINO ACIDS). Q-band (in ESR) See ELECTRON SPIN RESONANCE. Q bases Bases formed by the modification of guanine in tRNA; they contain a pentenyl ring attached (via NH) to the methyl group of N-methylguanine. An example is queuine, the Q base of QUEUOSINE. (See also Y BASES.) Q-cycle (protonmotive Q-cycle) A hypothetical pathway originally proposed (as part of the classical respiratory LOOP MODEL) to account e.g. for proton extrusion at Complex III of the mitochondrial ELECTRON TRANSPORT CHAIN; this pathway requires the presence of oxidized and reduced forms of ubiquinone (UQ and UQH2 , respectively) and the free radical, semiquinone (UQH). In one form of the Q-cycle, an electron which enters the matrix side of Complex III is taken up, together with one proton from the matrix side, by UQH – forming UQH2 . On passing to the cytoplasmic side, UQH2 undergoes oxidation to UQH – one proton being extruded, and one electron passing back to the matrix side via b-type cytochromes; this electron, together with a proton from the matrix side, reduces UQ, thus regenerating UQH at the matrix side. At the cytoplasmic side, the UQH formed from UQH2 undergoes oxidation to regenerate UQ, one proton being extruded, and one electron passing to cyt c1 . [Thermodynamic and kinetic considerations of Q-cycle mechanisms: JBB (1985) 17 51–64.] Q enzyme A BRANCHING ENZYME which can convert amylose into an amylopectin-type polysaccharide; it cannot introduce branches into amylopectin. It occurs in certain algae and in higher plants. Q fever In man, an acute disease caused by Coxiella burnetii (see COXIELLA). Infection may occur e.g. by the inhalation of contaminated dust or the ingestion of contaminated milk. After an incubation period of 2–3 weeks there is a sudden onset with headache, malaise, fever, muscular pain, and (often) respiratory symptoms (pneumonitis); there is no rash. Complications (e.g. endocarditis) may occur but the disease is rarely fatal. Diagnosis may include e.g. serological tests and/or attempts to culture C. burnetii from blood or sputum samples. Tetracyclines and chloramphenicol have been used therapeutically. Reservoirs of infection occur e.g. in sheep and cattle and in argosid and ixodid ticks. [Minireview: JMM (1996) 44 77–78.] [Goat-associated Q fever in Newfoundland: EID (2001) 7 413–419.] QAC See QUATERNARY AMMONIUM COMPOUNDS. Qalyub group See NAIROVIRUS. Qiagen plasmid kit Any of several commercial kits (marketed by Qiagen GmbH, Hilden, Germany) used for isolating plasmids from bacteria (e.g. Escherichia coli ); up to 20 µg of plasmid DNA can be isolated with the ‘mini’ kit, and up to 10 mg can be isolated with larger kits. For E. coli (and other Gram-negative bacteria) the outer membrane is initially disrupted by a Tris–EDTA buffer. Then, controlled lysis of the cytoplasmic membrane with SDS (sodium dodecyl sulphate) permits release of plasmids and soluble proteins etc. (but not chromosomal DNA); contaminating RNA is digested with RNase A. SDS and proteins (but not plasmids) are precipitated in buffer, and a cleared lysate (containing the plasmids) is obtained by centrifugation. The spun lysate is passed through Qiagen anion-exchange resin; the resin is washed

to remove contaminants (and to remove any DNA-binding proteins), and the plasmids are eluted with buffer of appropriate pH and ionic strength. Plasmid DNA is precipitated with isopropanol; after centrifugation, the supernatant is discarded and the DNA is washed with 70% ethanol, air-dried, and suspended in buffer. qinghaosu (artemisinine, artemisinin, or arteannuin) An orally administered ANTIMALARIAL AGENT obtained from qinghao (Artemisia annua): a Chinese medicinal herb which has been used in China for at least 2000 years for the treatment of malaria [Chinese Medical Journal (1979) 92 811–816, cited in BMB (1982) 38 197]. Qinghaosu, a sesquiterpene lactone endoperoxide, is structurally distinct from all other known antimalarials. [Structure and chemical synthesis: PAC (1986) 58 817–824.] Qinghaosu is a rapidly acting blood schizonticide. It appears to be taken up selectively by infected erythrocytes [TRSTMH (1984) 78 265–270], and is apparently effective against Plasmodium falciparum (including strains resistant to chloroquine) and P. vivax. In culture, the drug rapidly inhibits protein synthesis and, subsequently, nucleic acid synthesis in P. falciparum. It seems that iron, within the parasite, activates the drug and gives rise to potent free radicals [TRSTMH (1994) 88 (supplement 1) 31–32]. Parenteral derivatives of qinghaosu, artemether and artesunate, have been used successfully for treating severe malaria e.g. in Indochina [BCID (1995) 2 309–330]. QPCR Quantitative PCR. qscR gene See QUORUM SENSING. quadrulus A four-rowed ribbon of cilia which runs, in a spiral, down the buccal cavity in Paramecium. quail disease Ulcerative enteritis in chickens, quail and pheasants; the causal agent is Clostridium colinum [IJSB (1985) 35 155–159]. quail pea mosaic virus See COMOVIRUSES. quailpox virus See AVIPOXVIRUS. Quantiplex See BDNA ASSAY. quarantine (1) The isolation of an individual (usually an animal), e.g. prior to entering a country, in order to determine whether or not that individual is suffering from a particular infectious disease; the period of isolation should be equal to or longer than the longest incubation period of the suspected disease. (From Italian quarantina = 40 days.) (2) The isolation of an individual suffering from an infectious disease in order to prevent the transmission of the disease to others. quarg (quark) A soft, unripened German cheese made from e.g. skim milk in much the same way as is cottage cheese (see CHEESE-MAKING (e)); a B-type LACTIC ACID STARTER and rennin are used to coagulate the milk protein. [AvL (1983) 49 83–84.] quartan malaria See MALARIA. quasi-equivalence See ICOSAHEDRAL SYMMETRY. quasispecies Of a given RNA virus: a population or sample which, as a consequence of the normal rate of replication error, is genetically heterogeneous; the range of genomes present will depend e.g. on the effects of selection. [See JINF (1997) 34 201–203.] quaternary ammonium compounds (QACs; quats; syn. onium compounds) A group of cationic surfactants used as ANTISEPTICS, DISINFECTANTS and PRESERVATIVES; they appear to act by 635

quats Quevedo disease See POD ROT. quinacrine A weakly basic, yellow fluorescent ACRIDINE dye (chromophore: 2-methoxy-6-chloro-9-aminoacridine) which has been used in the chemotherapy of e.g. malaria and giardiasis, and which is used as a chromosome stain. quinapyramine An anti-trypanosomal agent used e.g. for the treatment of dourine. quinghaosu See QINGHAOSU. quinic acid See CHLOROGENIC ACID. quinidine See QUININE. quinine An alkaloid obtained from the bark of the Cinchona tree; the sulphate and hydrochloride are ANTIMALARIAL AGENTS effective against the intraerythrocytic stage (blood schizont) of the parasite (Plasmodium). The diastereoisomer of quinine, quinidine, is used in place of quinine e.g. in the USA; compared to quinine it is less proteinbound but more cardiotoxic. Quinine appears to interfere with the parasite’s detoxification of ferriprotoporphyrin IX (FP). FP, formed when the parasite digests haemoglobin, is able to lyse the parasite unless it is detoxified by polymerization to insoluble granules of pigment (see HAEMOZOIN); such polymerization seems to involve a ‘haem polymerase’ [Nature (1992) 355 108–109], and the quinoline-type drugs (including e.g. quinine) possibly inhibit this enzymic activity. In a photoaffinity labelling experiment, quinine competitively inhibited the binding of a chloroquine analogue to specific proteins (perhaps ‘haem polymerase’?) within parasitized erythrocytes – suggesting the presence of targets common to the quinoline-type antimalarial agents [JBC (1994) 269 6955–6961]. 8-quinolinol Syn. 8-HYDROXYQUINOLINE. quinolobactin A SIDEROPHORE, from Pseudomonas fluorescens, whose synthesis is repressible by pyoverdin [AEM (2000) 66 487–492]. quinolone antibiotics A group of synthetic ANTIBIOTICS whose targets are GYRASE [gyrase-targeted antibiotics: TIM (1997) 5 102–109] and topoisomerase IV; each antibiotic contains a substituted 4-quinolone ring. The original antibiotics in this group – cinoxacin, NALIDIXIC ACID, OXOLINIC ACID and pipemidic acid – are active mainly against Gram-negative bacteria (but not against Pseudomonas aeruginosa); being rapidly excreted in urine, they have been used for treating UTIs caused by members of the Enterobacteriaceae. However, these drugs are not well absorbed when given orally and/or are readily inactivated in the body; they have a limited antibacterial spectrum, and resistance develops readily. Antibiotics subsequently added to the group were fluorinated, piperazinyl-substituted derivatives (so-called fluoroquinolones); they include ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin. Compared to the earlier quinolones, these drugs have a wider spectrum of activity (being active against e.g. Pseudomonas aeruginosa and certain Gram-positive cocci, including MRSA), are effective at much lower in vivo concentrations and are more stable in the body; moreover, resistance to these drugs develops less readily. [Comparison of activities of various quinolones: JAC (1985) 16 475–484, 485–490. Laboratory and clinical evaluation of pefloxacin: JAC (1986) 17 (supplement B) 1–118.] The fluoroquinolone danofloxacin has been used e.g. against Mycoplasma bovis in the treatment of CALF PNEUMONIA; little resistance to danofloxacin has developed in M. bovis, although significant levels of resistance have developed against other antiM. bovis antibiotics, including oxytetracycline, spectinomycin and the macrolide tilmicosin [VR (2000) 146 745–747].

disrupting the cytoplasmic membrane and (at high concentrations) by denaturing proteins. A QAC may be regarded as an ammonium halide with four substituents: a long-chain alkyl group (C8 to C18 for high antimicrobial activity) and short-chain alkyl and/or benzyl or heterocyclic groups. QACs are bacteriostatic at low concentrations, bactericidal at high concentrations. They are typically more active against Gram-positive than Gramnegative bacteria, are reported to be fungistatic, trypanocidal, and active against certain viruses, but have little or no activity against Mycobacterium tuberculosis, Pseudomonas aeruginosa and bacterial endospores. They have a DILUTION COEFFICIENT of 1, and are inhibited e.g. by low pH, organic matter (serum, faeces etc), anionic detergents, soaps, phospholipids, and certain cations (e.g. Ca2+ , Mg2+ ) which may compete for sites on the (negatively charged) cell surface. Various substances, (e.g. agar, glass) strongly adsorb QACs. QACs are used e.g. for pre-operative skin cleansing and surgical dressings, and for the disinfection of equipment used in the food and dairy industries. They include e.g. benzalkonium chloride (= Zephiran, a mixture of alkyldimethylbenzylammonium chlorides) – used e.g. as a preservative in ophthalmic solutions; benzethonium chloride (a substituted benzalkonium chloride); Cetrimide (= Cetavlon, a mixture of hexadecyl- (cetyl-), tetradecyl- and dodecyl-trimethylammonium bromides); cetylpyridinium chloride (1-hexadecylpyridinium chloride); CTAB (cetyltrimethylammonium bromide); Domiphen bromide (dodecyldimethyl-2-phenoxyethylammonium bromide). quats QUATERNARY AMMONIUM COMPOUNDS. Quayle cycle Syn. RMP PATHWAY. Queensland tick typhus In man, a tick-borne disease caused by Rickettsia australis. Quellk¨orper Within the closed ascocarps of certain fungi: a gelatinous mass of cells believed to be involved in the rupture of the (mature) ascocarp wall. quellung phenomenon A phenomenon – originally described by Neufeld for Streptococcus pneumoniae – in which the bacterial CAPSULE becomes more easily observable (appears darker) in the presence of antiserum specific for the capsular material. Antibodies mark the outer limit of the capsule by combining with its outermost layer. Since in the absence of antibodies the capsule may be invisible by microscopy, antibodies were originally thought to cause the capsule to swell (Quellung = swelling); in fact, little actual swelling appears to occur. quench-freezing The process of rapidly FREEZING a specimen by plunging it into a suitable CRYOGEN. Querbalken Lysozyme-sensitive crossbands in the prosthecae of species of Asticcacaulis and Caulobacter. quercetin A mutagenic flavonol glycoside pigment widely distributed in plants; it binds non-covalently to and inhibits (F0 F1 )type PROTON ATPASES. queuine See QUEUOSINE. queuosine (Q) A hypermodified guanosine derivative (7-[4,5cis-dihydroxy-1-cyclopentene-3-aminomethyl]-7-deazaguanosine) present in the wobble position (see WOBBLE HYPOTHESIS) of tRNAs for aspartic acid, asparagine, histidine and tyrosine in most prokaryotic and eukaryotic organisms investigated (but not in Saccharomyces cerevisiae). The Q BASE queuine pairs with either C or U. Modification of G to Q in the wobble position of a tRNA anticodon can influence codon selection by the tRNA in vivo [EMBO (1985) 4 823–827]. In eukaryotes, the tRNA Q content is variable and correlates with certain developmental changes [e.g. in Dictyostelium discoideum: JGM (1984) 130 135–144]. 636

quinones H C

CH2 CH2 N HO CH

CH2 CH3 NHCHCH2CH2CH2N(C2H5)2

CH3O N

N

Cl

Quinine

Chloroquine

H HO

HOCCH2CH2N(C4H9)2

HC

Cl

N H N

CF3

CF3

CF3 Mefloquine

Cl

Halofantrine CH3

HNCH(CH2)3NH2 N CH3O Primaquine QUININE and some other antimalarial drugs (see MALARIA for further details of these and other antimalarials). Reproduced from Antimicrobial Drug Action, Figure 7.3, page 123, R.A.D. Williams, P.A. Lambert & P. Singleton (1996) copyright Bios Scientific Publishers, UK (ISBN 1-872748-81-3) with permission from the publisher.

Some strains of Acinetobacter baumannii resistant to quinolone antibiotics (ciprofloxacin, nalidixic acid) have mutations in the gyrA (gyrase) and/or parC (topoisomerase IV) genes [RMM (1998) 9 87–97]; a similar mechanism of resistance has also been found in other species. Mutations in gyrase and topoisomerase IV are commonly found in the socalled quinolone resistance-determining regions: a particular sequence in the gyrA gene and a homologous sequence in parC. However, in Streptococcus pneumoniae, mutations in gyrA and parE (the gene encoding the other subunit in topoisomerase IV) have been found in a strain showing increased resistance to certain of the newer fluoroquinolones (moxifloxacin, sparfloxacin, grepafloxacin) but with only slight (or no) increased resistance to older fluoroquinolones (ciprofloxacin, pefloxacin) – and with greater sensitivity to novobiocin [AAC (2001) 45 952–955]. Other modes of resistance to quinoline antibiotics include reduced permeability of the cell envelope and efflux mechanisms. [Efflux-mediated resistance to fluoroquinolones in Gramnegative bacteria: AAC (2000) 44 2233–2241.]

The activities of some of the newer fluoroquinolones (including gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin and trovafloxacin) have been ascertained against ciprofloxacinresistant Streptococcus pneumoniae; these newer drugs were found to have improved activities compared with that of ciprofloxacin [AAC (2001) 45 1654–1659]. Various drugs (including gatifloxacin, gemifloxacin, grepafloxacin, levofloxacin and moxifloxacin) are discussed in the Report of the 7th International Symposium on New Quinolones (Edinburgh, June 10–12th, 2001) [JAC (2001) 47 (supplement S1)]. (See also CcdB in F PLASMID.) quinomycins See QUINOXALINE ANTIBIOTICS. quinone antifungal agents A group of agricultural ANTIFUNGAL AGENTS which includes e.g. BENQUINOX, CHLORANIL, DICHLONE and DITHIANON. quinones Aromatic dioxo (diketo) compounds which are typically coloured (usually yellow, orange or red) and are e.g. constituents of many natural pigments. Quinones are classified as benzoquinones, naphthoquinones etc according to the nature of the aromatic ring system. Microorganisms contain a range of 637

quinoprotein quinoprotein A class of ENZYME in which the prosthetic group is pyrrolo-quinoline quinone (PQQ): 2,7,9-tricarboxy-1H pyrrolo(2,3f )-quinoline-4,5-dione. Quinoproteins include e.g. methanol dehydrogenase (in which PQQ is called methoxatin), and glucose dehydrogenase (EC 1.1.99.17). [PQQ and quinoproteins in microbial oxidations: FEMS Reviews (1986) 32 165–178.] (See also EXTRACYTOPLASMIC OXIDATION and METHYLOTROPHY.) quinovosamine 2-Amino-2,6-dideoxyglucose: a TRIFOLIIN Abinding component of LPS in strains of Rhizobium leguminosarum biotype trifolii. quinoxaline antibiotics Bifunctional INTERCALATING AGENTS (f ca. 48° ), each having two quinoxaline 2-carboxylic acid chromophores linked by a cyclic octapeptide dilactone containing Dand L-amino acids; the peptide has a central cross-bridge (thioacetal in the quinomycins, disulphide in the triostins). The two parallel chromophores project from the (relatively rigid) peptide ring and intercalate at sites two base pairs apart; the peptide ring seems to fit into the minor groove of the DNA. The quinoxalines echinomycin (= quinomycin A) and triostin A differ only in the nature of the cross-bridge; both show some preference for GC-rich natural DNAs. TANDEM (des-N-tetramethyltriostin A: a synthetic analogue of triostin A) shows a marked preference for AT-rich sequences. Quinoxalines are antimicrobial and antitumour agents; they inhibit the chain elongation stage of DNA-directed RNA synthesis. Quinqueloculina See FORAMINIFERIDA. quinsy Peritonsillar ABSCESS (usually due to Streptococcus pyogenes) – a complication of TONSILLITIS. quintozene (PCNB) Pentachloronitrobenzene, an agricultural antifungal agent used mainly for the treatment of soil; it is effective against a number of soil- and seed-borne diseases, e.g. DAMPING OFF, various rots of bulbs. Quintozene is insoluble in water and is used as a dust; it is very stable and has low volatility – hence it is very persistent in the soil. (cf. TECNAZENE, DICLORAN.) quinupristin/dalfopristin (RP 59500; Synercid ) A bactericidal antibiotic (within the STREPTOGRAMIN group) which is active against e.g. most streptococci (including S. pneumoniae), MRSA, and Enterococcus faecium (E. faecalis is resistant); it has a long POST-ANTIBIOTIC EFFECT [Drugs (1996) 51 (supplement 1) 31–37]. [In vitro activity against Staphylococcus aureus: JAC (1997) 39 53–58.] Quinupristin/dalfopristin (administered intravenously) has been conditionally licenced in Europe and the USA; it has been useful e.g. for treating vancomycin-resistant infections. Sideeffects include arthralgia and myalgia. [Quinupristin/dalfopristin (when to use?): JAC (2000) 46 347–350.] qundai-cai See UNDARIA. quorum sensing The phenomenon in which cells express particular characteristic(s) only when present as a population whose density is above a certain minimum (quorum). (Here, the ‘density’ of a population refers to the number of cells per unit volume.) Thus, in some cases, cells in a high-density population exhibit characteristics which are absent when the same cells are in a low-density population. One example of quorum sensing is that of Photobacterium fischeri (sometimes referred to as Vibrio fischeri ). P. fischeri can occur either as a free-living organism (in low-density populations), or as a symbiont in high-density populations within the light-emitting organs of certain fish; as a symbiont, P. fischeri produces a blue-green BIOLUMINESCENCE – whereas in the freeliving state (low-density population) it produces little or no light.

quinones, the nature of which can be a useful taxonomic feature [in bacteria: MR (1981) 45 316–354].

OH

O CH3O

CH3

CH3O

R

(a)

+2e−, +2H

−2e−, −2H

CH3

CH3O

+ +

O

R

CH3O (b)

OH

O CH3 R (c)

O

QUINONES. (a) A ubiquinone. (b) The reduced form of a ubiquinone: a hydroquinone. (c) A menaquinone (a vitamin K2 ). R = −[CH2 .CH=C(CH3 ).CH2 ]n H.

Benzoquinones include plastoquinones (2,3-dimethylbenzoquinones) and ubiquinones (coenzymes Q); the latter are 2,3dimethoxy-5-methyl-1,4-benzoquinones with a variable-length isoprenoid side-chain at the 6-position. (Ubiquinones are given various designations based either on the number of isoprenoid units or on the number of carbon atoms in the side-chain: e.g., a ubiquinone with a side-chain containing 8 isoprenoid units may be designated ubiquinone-8, UQ-8, UQ8 , coenzyme Q8 , or ubiquinone-40, UQ-40, etc.) [Book ref. 89.] Naphthoquinones include e.g. various pigments and toxins (see e.g. NAPHTHAZARINS and XANTHOMEGNIN), as well as the K vitamins: derivatives of 2-methyl-1,4-naphthoquinone (vitamin K3 , menadione) in which the 3-position may be substituted with a mono-unsaturated phytyl chain (in vitamin K1 , = phylloquinone) or with a variable-length polyisoprene chain (in vitamins K2 , = menaquinones). (Menaquinone terminology resembles that for ubiquinones: hence, e.g., menaquinone-6, MK-6, MK-30, vitamin K2(30) etc.) Some bacteria (e.g. members of the PASTEURELLACEAE) contain menaquinones which lack the 2-methyl group (2-demethyl-vitamins K2 ). In mammals, vitamins K are important components of the blood coagulation system; mammals cannot synthesize these vitamins, depending on diet (particularly green plants) and on the bacterial flora of the gut (particularly Escherichia coli and Bacteroides spp) for an adequate supply. Quinones can be reversibly reduced to hydroquinones; they function e.g. in aerobic and anaerobic ELECTRON TRANSPORT CHAINS, in PHOTOSYNTHESIS, etc. For example, E. coli synthesizes both ubiquinone-8 and menaquinone-8 in proportions which depend on growth conditions; the quinones function as carriers of reducing equivalents between dehydrogenases and terminal enzyme complexes (cytochrome oxidases, nitrate reductase, or fumarate reductase) – ubiquinone reduction involving the gain of two electrons followed by the addition of two protons. The menaquinone is specifically required for FUMARATE RESPIRATION, and is also required for the anaerobic synthesis of e.g. pyrimidines (linking dihydro-orotate dehydrogenase with fumarate reductase in the anaerobic synthesis of uracil). (See also QUINOPROTEIN.) 638

quorum sensing (Bacterial bioluminescence is used by the fish to signal to one another.) The mechanism of quorum sensing involves certain secreted molecules which, only in high-density populations of the secreting cell, reach a threshold concentration which is sufficient to trigger specific gene(s) within the cells. The secreted signalling molecule is referred to as an autoinducer because the cells themselves produce it. Autoinducers are low-molecular-weight molecules. Different bacteria may produce different types of autoinducer that regulate different characteristics; however, in some cases different species may produce the same type of autoinducer for regulating different genes. A given species may produce a range of autoinducers to control the expression of various characteristics. In many Gram-negative bacteria, the autoinducer is an N acyl-L-homoserine lactone (AHL). [AHL-based quorum sensing: TIBS (1996) 21 214–219.] In general, AHLs appear to act by diffusing into the cell and binding to an appropriate cytoplasmic protein involved in regulating the transcription of relevant gene(s). In the case of P. fischeri, an AHL triggers the lux operon (see BIOLUMINESCENCE). [Evolution of LuxI and LuxR as regulatory molecules in quorum sensing: Microbiology (2001) 147 2379–2387.] Strain CV026 of Chromobacterium violaceum is an inducernegative mutant which produces VIOLACEIN when exposed to exogenous inducers, including all tested molecules of AHL and AHT (N-acylhomocysteine thiolactone) with N-acyl sidechains between C4 and C8 ; this mutant strain can therefore be used as a biosensor for detecting a range of inducer molecules [Microbiology (1997) 143 3703–3711]. In Pseudomonas aeruginosa the genes encoding certain virulence factors are regulated by at least two quorum sensing systems – the las and rhl systems that involve different AHL autoinducers; these systems appear to act hierarchically, i.e. one system is always activated before the other [TIM (1997) 5 132–134]. The product of gene qscR appears to be a negative regulator of quorum-sensing-controlled genes; it probably acts by repressing gene lasI (which encodes N-3-(oxododecanoyl) homoserine lactone) [PNAS (2001) 98 2752–2757]. Quorum sensing has been reported to regulate expression of the type III PROTEIN SECRETION system in both EHEC and EPEC strains of Escherichia coli – this involving induction of genes in the LEE PATHOGENICITY ISLAND; regulation of the LEE operons involves an autoinducer encoded by gene luxS. To account for the unusually low infectious dose (low-density population) of E. coli O157:H7, it has been suggested that inducer may

be derived from non-pathogenic strains of E. coli in the gut [PNAS (1999) 96 15196–15201]. The existence of quorum sensing mechanisms in pathogens may permit therapy based on inhibition of autoinducers. Interestingly, the macrolide antibiotic AZITHROMYCIN has been reported to inhibit quorum sensing in Pseudomonas aeruginosa strain PAO1, the result (possibly advantageous e.g. in CYSTIC FIBROSIS patients [Lancet (1998) 351 420]) being an inhibition of the pathogen’s production of virulence factors [AAC (2001) 45 1930–1933]. In Burkholderia cepacia there is evidence that swarming, and the maturation of biofilms, are aspects of the organism’s physiology that are regulated by a quorum-sensing mechanism [Microbiology (2001) 147 2517–2528]. In Escherichia coli O157:H7 quorum sensing has been reported to be a global regulatory mechanism involved in basic physiological functions as well as in the formation of virulence factors [JB (2001) 183 5187–5197]. Interestingly, studies on Pseudomonas aeruginosa indicate that the stringent response (see STRINGENT CONTROL sense 1) can activate quorum sensing independently of cell density, a feature which may be important in nutrient-limited conditions during infection [JB (2001) 183 5376–5384]. In Gram-positive bacteria, the signalling molecules used in quorum sensing are generally peptides (= pheromones). Thus, for example, when cells of Bacillus subtilis grow to high density, at least two types of pheromone accumulate in the extracellular environment: ComX and CSF. ComX promotes competence in TRANSFORMATION by activating a TWO-COMPONENT REGULATORY SYSTEM; it causes autophosphorylation of a membrane-bound histidine kinase (ComP) which, in turn, phosphorylates (activates) the transcription factor ComA – a regulator of the comS gene that is required for competence. The pheromone CSF appears to be one of a number of factors involved in the initiation of sporulation. It is taken up by cells via an ATP-dependent oligopeptide permease transport system in the cytoplasmic membrane; within the cytoplasm CSF apparently inhibits the activity of certain phosphorylases that would otherwise de-phosphorylate Spo0F∼P, thereby promoting the phosphorelay and sporulation. In Enterococcus faecalis, conjugation involves secretion of pheromones by potential recipients. [Peptide signalling (review): TIM (1998) 6 288–294.] In the (dimorphic) fungus Candida albicans, farnesol (a sesquiterpene alcohol) acts as a quorum-sensing molecule whose effect is reported to be inhibition of yeast-to-mycelium conversion [AEM (2001) 67 2982–2992].

1. Words in SMALL CAPITALS are cross-references to separate entries. 2. Keys to journal title abbreviations and Book ref. numbers are given at the end of the Dictionary. 3. The Greek alphabet is given in Appendix VI. 4. For further information see ‘Notes for the User’ at the front of the Dictionary.

639

Dictionary of Microbiology and Molecular Biology, Third Edition Paul Singleton and Diana Sainsbury © 2006 John Wiley & Sons Ltd. ISBN: 0-470-03545-5

R R

¨ (1) RONTGEN (q.v.). (2) (in cell cycle) See CELL CYCLE. (3) Arginine (see AMINO ACIDS). R antigen (streptococcal) Syn. R PROTEIN. R body A refractile, intracellular structure which occurs e.g. in certain bacterial endosymbionts of protozoa (see CAEDIBACTER) and which appears to confer killer characteristics on the protozoan host cell. An R body consists of a proteinaceous ribbon, ca. 0.2–0.5 µm wide and ca. 10–15 µm in length, which is rolled up to form a cylinder; under negative phase-contrast MICROSCOPY it appears as a bright ring or (when viewed in section from the side) as a pair of parallel rods. Its presence within a bacterial cell is apparently associated with the presence of plasmid(s) and/or phage(s). R bodies appear to unroll in the food vacuoles of sensitive paramecia; unrolling appears to occur from the inside or outside of the coil according to the species of the bacterium of origin. R bodies have also been found in free-living strains of Pseudomonas which are toxic for sensitive paramecia [Arch. Micro. (1979) 121 9–15] and in a free-living Pseudomonas-like bacterium [JGM (1986) 132 2801–2805]. r-chromatin Chromatin containing rRNA genes. R factor (1) See R PLASMID. (2) Release factor: see PROTEIN SYNTHESIS. R-glucan Alkali-resistant (i.e. alkali-insoluble) glucans of fungal CELL WALLS. R loop (mol. biol.) A single-stranded loop of DNA formed when a short ssRNA molecule pairs with a complementary region of one strand of a dsDNA molecule, displacing the corresponding region of the homologous strand (the R loop). An R loop can be observed by electron microscopy using the KLEINSCHMIDT MONOLAYER TECHNIQUE. If the ssRNA used is a mature mRNA derived from a SPLIT GENE, an intron in the DNA – having no homologous region in the mRNA – will appear as a loop of dsDNA extruded between two R loops (each R loop corresponding to one of the two adjacent exons); thus, R-looping can be used e.g. to detect introns in genes. (cf. D LOOP.) r plasmid See R PLASMID. R plasmid (formerly R factor, drug resistance factor etc) Any PLASMID which encodes resistance to one or more ANTIBIOTICS and/or to other antimicrobial agents (including e.g. heavy metal ions). A bacterium containing an R plasmid may express resistance e.g. by synthesizing a (plasmid-encoded) enzyme which destroys/modifies an antibiotic (see e.g. CHLORAMPHENICOL, bLACTAMASES) or which modifies the target site (see e.g. MLS ANTIBIOTICS), or by synthesizing a drug-resistant form of a target enzyme (see e.g. SULPHONAMIDES). A conjugative (= transmissible) R plasmid also contains genes which specify the intercellular transfer of the plasmid by CONJUGATION (sense 1b) (see also RTF); a non-conjugative (= non-transmissible) R plasmid does not specify its own conjugal transfer but it may be ‘mobilized’ by a conjugative plasmid. (Some authors refer to a non-conjugative R plasmid as an ‘r plasmid’.) R plasmids belong to various Inc groups (see INCOMPATIBILITY). R point (in cell cycle) See CELL CYCLE. r-protein Ribosomal protein: see RIBOSOME. R protein (R antigen) (in streptococci) A cell-surface protein found in streptococci of groups A, B, C and G. R protein is

only moderately immunogenic and is apparently not associated with virulence. It occurs in two antigenically distinct forms: R28 (trypsin-resistant) and R3 (trypsin-sensitive). (See also M PROTEIN and T PROTEIN.) R strain See SMOOTH–ROUGH VARIATION. r-strand (in adenoviruses) See ADENOVIRIDAE. R-TEM b-lactamase Syn. TEM-1 b-LACTAMASE. R1 plasmid A low-COPY NUMBER, IncFII CONJUGATIVE PLASMID (MWt ca. 60000) which occurs in enterobacteria; it encodes resistance to e.g. ampicillin, chloramphenicol, sulphonamides and streptomycin. Replication is promoted, at the origin, by the (plasmid-encoded) RepA protein, and the frequency of plasmid replication is controlled by the regulation of RepA synthesis. The main negative control exerted on RepA synthesis is carried out by the copA product, an unstable, constitutively produced micRNA (see ANTISENSE RNA), of half-life ca. 1–2 minutes, which binds to the complementary sequence (copT ) on the repA mRNA, thus inhibiting translation of the RepA protein; the inhibitory influence of the copA/copT system decreases with decrease in copy number – thereby providing a mechanism for stabilizing copy number. (CopA also has a role in INCOMPATIBILITY in IncFII plasmids.) It has been proposed that the level of repA expression is also affected by a region (designated 7k ) within the repA leader sequence; translation of (i.e., the presence of ribosomes in) this region, which overlaps the copT sequence, is believed to counteract the negative control of the copA/copT system [EMBO (1987) 6 515–522]. R6 plasmid An enterobacterial IncFII CONJUGATIVE PLASMID (COPY NUMBER: 1–2); it encodes resistance to e.g. chloramphenicol, streptomycin, sulphonamides and mercury. R6K plasmid A multicopy enterobacterial CONJUGATIVE PLASMID (ca. 38 kb) which carries genes specifying resistance to ampicillin and streptomycin. R6K apparently undergoes sequential bidirectional replication from any of three origins (designated a, b and g), all of which are located within a 4-kb region of the plasmid. Replication initiated at an origin apparently proceeds first in one direction, stopping at a specific termination site (ter ); re-initiation then occurs at the same origin and proceeds in the opposite direction to ter, thus completing replication of the plasmid. Initiation of replication at any of the three origins requires a trans-acting R6K-encoded DNA-binding protein (the p or Pi protein) and a region within the g-origin containing seven tandemly-arranged 22-bp direct repeats (ITERONS). Plasmids from which the g-origin has been deleted cannot be replicated even when p is supplied in trans; the a- and b-origins each appear to have a minimum functional size of ca. 2 kb which includes the seven iterons in the region of the g-origin. (Deletion of three or more of the iterons results in loss of plasmid replicability.) The p protein binds preferentially to the iterons and positively regulates initiation of replication from one of the origins (a, b or g). At high concentrations, p can also play a role in the negative regulation of R6K replication, apparently by specifically repressing replication from the g origin. (Experiments involving variation in the levels of p over a wide range suggest that the level of p in the cell is not responsible for controlling the copy number of R6K.) The p protein can also bind to the promoter–operator region of its own gene (pir, located near the g origin); this region 640

radiolaria contains an 8th iteron together with a pair of imperfect inverted repeats. The p-binding site overlaps the RNA polymerasebinding site at the pir promoter, and at high concentrations p can act as a repressor of its own synthesis. [Review: Book ref. 161, pp. 125–140; binding of p to R6K DNA: JMB (1986) 187 225–239.] R10 medium RAPPAPORT–VASSILIADIS BROTH. R18 plasmid See RP1 PLASMID. R46 plasmid An IncN PLASMID (ca. 52 kb) which encodes resistance to ampicillin, streptomycin, sulphonamides and tetracycline. (See also PARTITION and SOS SYSTEM.) R68 plasmid See RP1 PLASMID. R100 plasmid (syn. NR1 plasmid; R222 plasmid) An IncFII enterobacterial CONJUGATIVE PLASMID (COPY NUMBER: 1–2) that encodes resistance to e.g. chloramphenicol, streptomycin, sulphonamides and mercury. (The tetracycline-resistance gene is carried on a TRANSPOSON – see entry for Tn10.) The R100.1 derivative is a DRD PLASMID. R222 plasmid See R100 PLASMID. R1822 plasmid See RP1 PLASMID. Ra strain See SMOOTH – ROUGH VARIATION. rabbit fibroma virus See LEPORIPOXVIRUS. rabbit herpesvirus See GAMMAHERPESVIRINAE. rabbitpox virus See ORTHOPOXVIRUS. rabies (hydrophobia; lyssa) An acute, almost invariably fatal disease of man and animals – particularly carnivores, though most mammals can be infected. The rabies virus (see LYSSAVIRUS) is transmitted (in saliva) mainly by the bite of a rabid animal. The virus remains at the site of infection for a time before entering peripheral nerves and travelling along the nerves to the CNS. Rabies in man. Incubation period: usually 2–13 weeks, but may be 6 days to a year or more, depending e.g. on the distance between the site of infection and the CNS. Early symptoms are non-specific: fever, headache, malaise etc. These are followed by neurological symptoms, including excitability and pharyngeal spasms (triggered e.g. by attempts to drink or even by the sight of water – hence ‘hydrophobia’); periods of hyperactivity may alternate with periods of relative normality. Convulsions and paralysis precede death. (Occasionally, paralytic symptoms predominate, with little hyperactivity.) Lab. diagnosis: detection of the virus in saliva, CSF etc – e.g., by electron microscopy or by fluorescent antibody staining; when possible, confirmation of rabies in the animal which inflicted the bite – e.g., by postmortem detection of (pathognomonic) NEGRI BODIES and rabies virus. Rabies virus can be detected in brain samples by an rtPCR-based approach; an rtPCR–ELISA test has been evaluated on 60 isolates of rabies and rabies-related viruses [JVM (1997) 69 63–72]. Treatment: none is effective once the disease is established. Post-exposure prophylaxis includes thorough washing of the wound followed by treatment with both rabies antiserum (part of which is instilled directly into the wound) and rabies vaccine; pre-exposure vaccination may be given to individuals at special risk (e.g. veterinarians, animal handlers). Inactivated vaccines are used for human treatment; these include duck embryo vaccine (DEV) (prepared from virus grown in embryonated duck eggs), and human diploid cell vaccine (HDCV) (prepared from virus grown in cultures of human diploid embryo lung fibroblasts). These vaccines are safer than those prepared from animal nerve tissue (e.g. SEMPLE VACCINE). Rabies in animals. Dogs and other carnivores (wolves, foxes etc) may initially show excitement, violence etc (‘furious rabies’), followed by depression and paralysis (‘dumb rabies’).

In cattle and horses, symptoms are variable. In vampire bats (important reservoirs of infection in Central and South America) only the dumb form occurs. Vaccines for use in animals may be live attenuated (see e.g. FLURY VIRUS) or inactivated. (cf. AUJESZKY’S DISEASE.) rac prophage See RECF PATHWAY. race (1) (mycol.) PHYSIOLOGICAL RACE. (2) A non-specific designation which may refer e.g. to a STRAIN or a VARIETY. racket mycelium Syn. RACQUET MYCELIUM. racquet mycelium (racket mycelium) In DERMATOPHYTES: mycelium composed of hyphal cells which have terminal swellings and which thus resemble long-handled tennis racquets. rad Radiation absorbed dose: a unit of absorbed radiation equal to 100 ergs of energy absorbed by 1 g of material (0.01 joules absorbed by 1 kg). (See also GRAY and IONIZING RADIATION; cf. ¨ RONTGEN .) RadA protein In members of the Archaea: a protein apparently analogous to the bacterial RecA protein [GD (1998) 12 1248–1253]. radappertization Irradiation of food with levels of IONIZING RADIATION sufficient to inactivate the spores of Clostridium botulinum. (cf. RADICIDATION; RADURIZATION.) Radar See PROPICONAZOLE. radiation (in disinfection and sterilization) See IONIZING RADIATION; MICROWAVE RADIATION; ULTRAVIOLET RADIATION. radicidation Irradiation of food with levels of IONIZING RADIATION sufficient to inactivate certain non-sporing pathogens (e.g. Salmonella spp). (cf. RADURIZATION; RADAPPERTIZATION.) radioallergosorbent test See RAST. radioautography Syn. AUTORADIOGRAPHY. radioimmunoassay (RIA) A highly sensitive IMMUNOASSAY by which antigens or antibodies are quantified using radioactive labelling. Antibody assay. Essentially, the antiserum under test is allowed to react with excess homologous antigen (radiolabelled e.g. with 125 I), and the immune complex is separated from any uncombined antigen – e.g. by precipitation (as in the FARR TECHNIQUE); the amount of antigen in the immune complex is then determined from the level of radioactivity in the complex, and the amount of antibody can hence be calculated. Antigen assay. This is based on the fact that the proportion of a fixed amount of radiolabelled antigen which combines with a fixed amount of homologous antibody depends on the amount of unlabelled antigen present: the more unlabelled antigen present, the smaller the proportion of labelled antigen – and the lower the level of radioactivity – in the immune complex. Thus it is possible to construct a standard curve for the amount of unlabelled antigen corresponding to given levels of radioactivity in the immune complex. In antigen assays, the antigen to be quantified is the unlabelled antigen, the amount of which can be derived from the standard curve. (cf. IMMUNORADIOMETRIC ASSAY.) radioimmunosorbent test See RIST. radiolaria A group of free-living, marine, mostly planktonic protozoa (superclass ACTINOPODA) in which the cells are typically more or less spherical ( ca. 10 µm (e.g. those of Alternaria and Fusarium) tend to be trapped in the nose, but may reach the bronchi during mouth-breathing; such spores may induce e.g. a TYPE I REACTION. Spores 5–10 µm (formed e.g. by many species of Cladosporium and Mucor ) may be deposited in the bronchi or bronchioles where they may incite attacks of asthma in susceptible individuals; spores of this size may even penetrate into the alveoli if an individual is exposed to very large numbers of spores. Spores < 5 µm (e.g. those formed by species of Aspergillus and Penicillium, and by many actinomycetes) may reach the alveoli; the spores of actinomycetes are commonly implicated in certain types of EXTRINSIC ALLERGIC ALVEOLITIS. (See also BODY MICROFLORA and e.g. BRONCHITIS; COMMON COLD; CYSTIC FIBROSIS; PNEUMONIA.) response regulator See TWO-COMPONENT REGULATORY SYSTEM. resting spore (winter spore) (mycol.) A thick-walled spore, particularly one formed by a sexual process, which germinates only after an extended period of dormancy – e.g. an overwintering teliospore. (cf. SUMMER SPORE.) restricted transduction See TRANSDUCTION. restriction endonuclease (REase, RE; restriction enzyme) An ENDONUCLEASE which binds to dsDNA, usually at a specific recognition sequence (= recognition site), and typically makes a single cut in each strand – provided that specific bases at that site are unmethylated (for some REs) or methylated (for others); the cleaved duplex may exhibit STICKY ENDS or BLUNT-ENDED

DNA,

according to RE. Some REs have no unique recognition site, some have several. DNA may be cleaved within the site or outside it; some REs (e.g. BaeI) cut on both sides, excising a segment that includes the recognition site. (See also STAR ACTIVITY.) REs with various specificities have been isolated from a wide range of prokaryotes. (In some cases, REs from different species recognize the same nucleotide sequence: see ISOSCHIZOMERS.) An RE has a three-letter designation (based on the name of the host species) followed by a strain designation and/or a Roman numeral that indicates a particular RE from a given strain or species: see table for examples; there is currently a trend to avoid italics [RE nomenclature: NAR (2003) 31 1805–1812]. Recognition sequences are written 5′ -to-3′ (sequence for one strand only); an arrow (or stroke) shows a cleavage site (if within the recognition site). What purpose do REs serve in their host cells? The main role seems to be protection against ‘foreign’ DNA – particularly phage DNA [MR (1993) 57 434–450]. However, this protective mechanism is not always effective; for example, some phages encode specific inhibitors of REs. Moreover, antirestriction enzymes are encoded by certain plasmids [JB (1992) 174 5079–5085], and resistance to restriction enzymes is a typical feature of conjugative transposons [e.g. ARM (1995) 49 367–397]. Several distinct types of RE are recognized. Type I REs can methylate and cut DNA. ATP-dependent cleavage occurs outside the recognition sequence at a nonspecific site; the enzyme may bind to its recognition site while DNA is passed through another part of the enzyme until a cleavage site is reached. Example: EcoK1. [New type 1 REs from Escherichia coli: NAR (2005) 33 (13) e114.] Type II REs generally recognize a specific sequence and cleave both strands, independently of ATP, at a particular location in or near the recognition site; each strand is left with a 5′ -phosphate terminus and a 3′ -hydroxyl terminus. These REs are useful in recombinant DNA technology owing to their ability to cut DNA precisely; >3500 are now known. Subtypes of type II REs include: IIA. REs that recognize asymmetric sites. IIB. REs that cut on both sides of the recognition site – e.g. BaeI, whose recognition (underlined)/cutting sites are: /(10/15)AC(4N)GTAYC(12/7)/ in which 4N = any four nucleotides, Y = C or T; this strand is cut 10 nucleotides upstream, its complementary strand 15 nucleotides upstream – 12/7 indicating downstream cutting sites for both strands. IIC. REs with cutting and methylation functions combined in a single polypeptide. IIE. REs which cut at the recognition site but need interaction with another copy of that site in order to function. IIF. REs that bind to, and cut, both copies of the recognition site. IIM. REs which cut at (fixed) sites where there is a specific pattern of methylation – e.g. DpnI. (cf. Type IV, below.) IIP. REs with a fixed cutting site within, or very close to, the symmetrical (palindromic) recognition site – e.g. EcoRI. Type III. REs that interact with two inversely orientated, non-palindromic sites; cleavage, at a distance from one of the sites, requires ATP-dependent translocation. Examples: EcoP1l, EcoP15l. Type IV. REs with methylated recognition sites but which (unlike the IIM REs) apparently cut without specificity. 654

restriction–modification system RESTRICTION ENDONUCLEASES (REs): some examplesd RE

Source (organism)

Recognition sequencea

AatII AluI ApaI BamHI BclI BglII BssHII DraI EcoRI EcoRV HindIII HinfI HpaI HpaII KpnI MluI MspI NarI NcoI NotI NruI PalI PstI PvuI SacII SalI Sau3AI ScaI SmaI SnaBI SpeI SrfI TaqI XbaI

Acetobacter aceti Arthrobacter luteus Acetobacter pasteurianus Bacillus amyloliquefaciens Bacillus caldolyticus Bacillus globigii Bacillus stearothermophilus Deinococcus radiophilus Escherichia coli Escherichia coli Haemophilus influenzae Haemophilus influenzae Haemophilus parainfluenzae Haemophilus parainfluenzae Klebsiella pneumoniae Micrococcus luteus Moraxella sp Nocardia argentiensis Nocardia corallina Nocardia otitidis Nocardia rubra Providencia alcalifaciens Providencia stuartii Proteus vulgaris Streptomyces achromogenes Streptomyces albus Staphylococcus aureus Streptomyces caespitosus Serratia marcescens Sphaerotilus natans Sphaerotilus sp Streptomyces sp Thermus aquaticus Xanthomonas campestris var badrii Xanthomonas campestris var holcicola

GACGT/C AG/CT GGGCC/C G/GATCC T/GATCA A/GATCT G/CGCGC TTT/AAA G/AATTC GAT/ATC A/AGCTT G/ANTC GTT/AACb C/CGG GGTAC/C A/CGCGT C/CGG GG/CGCC C/CATGG GC/GGCCGCc TCG/CGA GG/CC CTGCA/G CGAT/CG CCGC/GG G/TCGAC /GATC AGT/ACT CCC/GCCb TAC/GTA A/CTAGT GCCC/GGGCc T/CGA

Bacillus sphaericus

/(10/15) AC(4N)GTAYC(12/7)/

XhoI BaeI a b c d

T/CTAGA C/TCGAG

5′ -to-3′

Recognition sequence in one strand (in the direction); the cutting site is shown as ′ /′ . A = adenine; C = cytosine; G = guanine; T = thymine. Produces ‘blunt-ended’ cuts. The eight-nucleotide sequence of a ‘rare-cutting’ enzyme. The proposed new nomenclature uses a non-italic format [NAR (2003) 31 1805–1812]. Currently, the literature refers to REs in both italic and non-italic formats. Modified from Table 2.1, page 18, in DNA Methods in Clinical Microbiology, Paul Singleton (2000) copyright Kluwer Academic Publishers, Dordrecht, The Netherlands (ISBN 0-79236307-8) with kind permission from the publisher. specific enzyme(s) in a manner characteristic of the particular bacterial strain, the modification serving to protect the DNA against enzymic degradation (‘restriction’) by the cell’s own endonucleases. Modification generally involves a specific pattern of methylation of nucleotide residues in the DNA (see DNA METHYLATION); using S-adenosylmethionine as methyl donor, the methylation enzymes (‘methylases’) act on dsDNA in which one or both strands are unmodified. The sites at which modification occurs are also recognized by corresponding

Some nicking enzymes (which cut one strand of dsDNA) resemble REs [e.g. BstNBI: NAR (2001) 29 2492–2501]. In some cases the recognition site of an RE can be chemically modified such that the enzyme cuts one specific strand of dsDNA; this approach is used e.g. in SDA. restriction endonuclease analysis See DNA FINGERPRINTING. restriction fragment length polymorphism See RFLP. restriction–modification system (R–M system) The system, present in many bacteria, in which DNA is modified by 655

restriction point (REs); the REs cannot cleave DNA in which these sites have been modified in one or both strands. Modification does not interfere with normal base-pairing, so that semiconservative replication of fully modified dsDNA will result in two duplexes, each containing one (modified) parent strand and one unmodified daughter strand. The modified parent strand protects the duplex from restriction, and the daughter strand is modified before further DNA replication; thus, DNA susceptible to restriction does not normally occur in the cell. However, if ‘foreign’ DNA lacking the modification pattern of the strain enters the cell (e.g. by conjugation, transformation, phage infection etc) it will generally be degraded. (See also HOST-CONTROLLED MODIFICATION.) Certain bacteriophages encode their own R–M systems: see e.g. T-EVEN PHAGES and BACTERIOPHAGE MU. restriction point (in cell cycle) See CELL CYCLE. restrictive conditions See CONDITIONAL LETHAL MUTANT. resupinate (mycol.) Refers to a fruiting body which forms a crust on the surface of the substratum, the spore-bearing surface being outermost. reticle See MICROMETER. reticulate body See CHLAMYDIA. reticule See MICROMETER. reticuloendotheliosis viruses See AVIAN RETICULOENDOTHELIOSIS VIRUSES. reticulopodium See PSEUDOPODIUM. reticulum See RUMEN. retinaculum apertum See SPIRA. retinal The purple component of various photosensitive proteins, e.g. BACTERIORHODOPSIN, HALORHODOPSIN, SLOW-CYCLING RHODOPSIN. The free retinal molecule is R−[CH=CH−C(CH3 )= CH]2 −CHO where R = 2,6,6-trimethyl-1-cyclohexenyl. (The corresponding alcohol, retinol, is vitamin A.) Linkage of the aldehyde group of retinal to a lysine residue in a halobacterial opsin creates a Schiff base. The synthesis of retinal in Halobacterium salinarium is inhibited e.g. when the organism is grown in the presence of nicotine. retort (in canning) See BATCH RETORT. retort pouch A flexible container used in the food processing industry as an alternative to the can. Typically, the pouch is made of a laminate consisting of aluminium foil sandwiched between an outer layer of polyester and an inner layer of e.g. polypropylene and nylon – the layers being bonded together by e.g. a polyester–isocyanate adhesive. (See also CANNING.) Retortamonadida An order of parasitic protozoa (class ZOOMASTIGOPHOREA). The cells, which are not bilaterally symmetrical, have two to four flagella, one of which is directed posteriorly along the ventral surface; cells lack mitochondria, Golgi apparatus, an axostyle and an undulating membrane. Genera: e.g. CHILOMASTIX, Retortamonas. Retortamonas See RETORTAMONADIDA. retrogressive development See CONIDIUM. retrohoming See INTRON HOMING. retroid viruses Viruses which resemble members of the RETROVIRIDAE in that they appear to employ a replication mechanism which involves reverse transcription of an RNA intermediate; retroid viruses include CAULIFLOWER MOSAIC VIRUS [review: TIBS (1985) 10 205–209] and members of the HEPADNAVIRIDAE. [Possible common evolutionary origin of hepatitis B virus and retroviruses: PNAS (1986) 83 2531–2535.]

retron In some strains of Escherichia coli (and certain other Gram-negative bacteria): a chromosomal genetic element encoding a REVERSE TRANSCRIPTASE structurally similar to that encoded by retroviruses. Retron-containing strains can synthesize a unique, branched, hybrid RNA–DNA molecule called multicopy single-stranded DNA (msDNA); in this molecule, the 5′ end of single-stranded DNA is linked (via a phosphodiester bond) to the 2′ position of an internal (i.e. non-terminal) guanosine residue in the RNA. Synthesis of msDNA involves the reverse transcriptase. A cell may contain many copies (up to 500) of msDNA, but the function of this molecule is unknown. Retrons seem to be ‘foreign’ or imported elements in E. coli. Retrons are referred to by a system of nomenclature in which the initials of the host species are followed by the number of bases in the DNA part of the corresponding msDNA; for example, Mx162 is a retron in Myxococcus xanthus in which the DNA of the msDNA contains 162 bases. Retrons also occur e.g. in Klebsiella, Proteus, Rhizobium and Salmonella [JB (1993) 175 4250–4254]. retroposon Syn. RETROTRANSPOSON. retroregulation (mol. biol.) A mode of post-transcriptional regulation in which expression of a gene is influenced by a cis-acting sequence downstream of the gene; if transcription proceeds into the cis-acting sequence, the resulting RNA is degraded and the gene is thus not expressed, whereas if transcription stops before the cis-acting sequence the RNA is not degraded and the gene is expressed. (See BACTERIOPHAGE l (int gene expression).) retrotranscription See REVERSE TRANSCRIPTASE. retrotransfer The flow of genetic material from recipient to donor during bacterial CONJUGATION. In Escherichia coli, retrotransfer was reported to be inhibited by streptomycin, and it occurred to a lesser extent during conjugation mediated by plasmids encoding strong SURFACE EXCLUSION; it has been suggested that retrotransfer is newly initiated conjugation between transconjugants and donors [JB (1993) 175 583–588] – an hypothesis supported by subsequent studies [JB (1996) 178 1457–1464]. retrotransposon (retroposon) A TRANSPOSABLE ELEMENT in which transposition involves a retrovirus-like process of reverse transcription with the formation of an RNA intermediate (see e.g. TY ELEMENTS). It has been argued that such TEs may be degenerate retroviruses [Cell (1985) 40 481–482, and 42 507–517]. (See also A-TYPE PARTICLES.) Retroviridae A family of enveloped ssRNA-containing animal viruses in which the genome is replicated via a dsDNA intermediate. Retroviruses have been isolated from a wide range of vertebrates – including mammals, birds and reptiles – and retrovirus-like particles have been observed e.g. in tapeworms and insects. Retrovirus infection in a given host may be asymptomatic or may result in any of various diseases, including e.g. pneumonia, anaemia, and malignant tumours and/or leukaemias. (See also AIDS.) Interestingly, retroviral RNA has been detected in the brain and CSF of individuals suffering from schizophrenia, suggesting a possible link [PNAS (2001) 98 4634–4639]. Transmission may occur horizontally and/or vertically (see below). The retrovirus virion is more or less spherical, ca. 80–120 nm diam., consisting of a nucleoprotein core (sometimes called the ‘nucleoid’) surrounded by an envelope derived largely from the host plasma membrane (or intracytoplasmic membranes). The core contains the viral REVERSE TRANSCRIPTASE and other viral proteins, the viral genome complexed with protein (also called the ‘nucleoid’) and low-MWt RNAs of host origin; the envelope contains a virus-encoded glycoprotein which determines the host

RESTRICTION ENDONUCLEASES

656

Retroviridae 5′ end R

3′ end U5 (−)PBS L

gag

pol

Cap

env

U3 P [ (+)PBS?]

R An

RETROVIRIDAE: Figure 1. The retrovirus genome, showing generalized features (not to scale). The genomes of some retroviruses have additional coding sequences not shown here. R U5 (−) PBS L gag pol env P U3 Cap An

= = = = = = = = = = =

Terminal redundancy. Sequence unique to the 5′ end (present at each end in proviral DNA). Primer binding site for the (−) DNA strand primer (a host tRNA). Leader sequence. Group-specific antigen genes (coding region for nucleocapsid proteins). Coding region for e.g. reverse transcriptase. Coding region for envelope glycoprotein. Polypurine tract and probable primer binding site for (+) DNA strand synthesis. Sequence unique to the 3′ end (present at each end in proviral DNA). ′ ′ 5′ Cap nucleotide (m7 G5 ppp5 . . .), added after transcription and not copied during DNA synthesis. ′ 3 Polyadenylate tract (e.g. ca. 100–200 nucleotides long), added after transcription and not copied during DNA synthesis.

range of the virus and is the target for neutralizing antibodies. All of the genetic information of the virus is encoded by a single piece of positive-sense ssRNA (ca. 3.5–9.8 kb) which has the structural features characteristic of eukaryotic mRNA (see Figure 1); however, in the virion the genome occurs in a 60S–70S dimer in which two identical (or similar) 30S–35S viral RNA molecules (‘monomers’) are held together at their 5′ ends by hydrogen bonds (i.e., the virion is ‘diploid’). The virions are sensitive to heat, lipid solvents and detergents, but are relatively resistant to UV- and X-irradiation. Retroviruses are classified according to their virion structure, host range, pathological effects (both on the host and in cell cultures) etc. Three subfamilies are recognized: LENTIVIRINAE, ONCOVIRINAE and SPUMAVIRINAE. Replication cycle. The mode of replication appears to be generally similar in the various types of retrovirus. Infection is initiated by interaction between the virus envelope glycoprotein and specific host cell surface receptors. In the host cytoplasm, a linear viral DNA is synthesized by the viral REVERSE TRANSCRIPTASE acting within the (presumably modified) infecting virus particle. Synthesis of the first (−) DNA strand is initiated at the (−) PBS at the 3′ boundary of the U5 region (see Figures 1 and 2), a host tRNA acting as a primer for initiation; most retroviruses use host tRNApro as primer, but mouse mammary tumour virus, visna virus, and the AIDS virus use tRNAlys . The viral RNA is degraded by viral RNase H (see RNASE H), and a second strand of DNA is synthesized using the (−) DNA strand as template. The resulting linear dsDNA molecule is slightly longer than the RNA template due to the duplication of regions U3 and U5 and the consequent generation of the long terminal repeats (LTRs: see Figure 2); the LTRs contain sequences necessary for the next stage in the cycle – integration of the viral DNA into the host cell DNA to form a provirus – and for the control of virus gene expression. In e.g. HIV (q.v.) the dsDNA is circularized, and one or more copies are inserted into the host cell DNA. Integration appears to be an essential step for replication of the retroviral genome, and, in general, integration may occur at random sites in the host DNA. For at least some retroviruses, two or more base pairs are lost from each LTR, prior to or during integration, and a short sequence of cellular DNA is duplicated such that the provirus is flanked by short direct repeats. (cf. TRANSPOSABLE ELEMENT.)

Once established in the host chromosome, a provirus may be quiescent or – depending e.g. on its location, on the strength of its promoters, on the physiological state of the cell, and on the presence or absence of specific regulators – may be transcribed to form progeny RNA genomes and mRNAs. The LTRs contain most of the signals for the regulation of transcription, including a promoter, an enhancer (in some retroviruses), and signals for termination of transcription and for polyadenylation of the transcript. Transcription appears to be carried out by host RNA polymerase II and is highly sensitive to a-amanitin. Primary transcripts are approximately the length of a viral RNA monomer; they are polyadenylated, and then processed further (e.g. by splicing). By convention, retroviral gene products are designated by their MWts × 10−3 prefixed by p, pp or gp for protein, phosphoprotein or glycoprotein, respectively: e.g. pp12gag = a phosphorylated product of gag, MWt ca. 12 × 103 ; polyprotein precursors are prefixed by Pr. The ‘genes’ gag, pol and env (all necessary for virus replication) encode polyproteins. The gag-encoded polyprotein is cleaved to form the 4 or 5 components of the virus core. The pol sequence is apparently expressed with gag such that a gagpol polyprotein precursor is formed (Pr180gag−pol in e.g. avian leukosis and murine leukaemia viruses); this precursor undergoes a series of cleavages, and the mature protein complex has reverse transcriptase, RNase H and DNA endonuclease activities. The env-encoded product is synthesized via a subgenomic spliced mRNA; the product is cleaved to remove a signal peptide, and is then glycosylated and cleaved to form the major protein component of the viral envelope. Envelope glycoproteins may continue to be synthesized until they saturate the plasma membrane receptors and thus prevent superinfection by any virus competing for those receptors. Nucleoprotein cores assembled in the cytoplasm subsequently bud through the plasma or internal membranes of the host cell; the released virions apparently undergo further maturation, involving e.g. condensation of the nucleoid, cleavage of gag and gag-pol proteins, etc. Transmission. Retroviruses may be transmitted by three distinct routes, not all of which can occur in all retroviruses. Horizontal transmission may occur e.g. by direct contact, via saliva, via insect vectors, etc, depending on virus. Vertical transmission may occur e.g. in avian retroviruses by infection of progeny via 657

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RETROVIRIDAE: Figure 2. Model for retroviral dsDNA synthesis from the ssRNA genome. (Thin lines = RNA; thick lines = DNA.) (Continued on page 659.)

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reverse gyrase all v-onc+ viruses are replication-defective: certain strains of ROUS SARCOMA VIRUS contain the oncogene v-src in addition to a full complement of viral genes.) All known v-onc+ viruses can transform at least some type(s) of cell in culture; by contrast, very few v-onc− viruses can transform cells in culture (cf. HTLV), although a few can cause CPE (e.g. vacuolization, syncytium formation, cell death) – usually only in certain types of cell. (See also e.g. AVIAN LEUKOSIS VIRUSES, FELINE LEUKAEMIA VIRUS, MURINE LEUKAEMIA VIRUSES; cf. FRIEND VIRUS and MCF VIRUSES.) retroviruses Viruses of the RETROVIRIDAE. retting The process by which cellulose fibres are released from the stems of flax (Linum usitatissimum), hemp (Cannabis sativa), or jute (Corchorus spp, Tiliaceae) by the action of pectinolytic fungi and bacteria; these organisms soften the stems, and the fibres are then separated by beating (‘scutching’). The fibres are used in the textile industry e.g. for the manufacture of linen (from flax), hessian (from hemp or jute), twine (from hemp) etc. In aerobic retting processes (‘dew retting’) the organisms involved include e.g. Cladosporium herbarum, Aureobasidium pullulans, and species of Cryptococcus, Rhizopus, Rhodotorula, Bacillus and Pseudomonas. In anaerobic processes the stems are submerged in water-tanks, and the main retting agents are Clostridium spp, especially C. felsineum. REV (REV-T, REV-A) See AVIAN RETICULOENDOTHELIOSIS VIRUSES. reversal reaction See LEPROSY. reverse CAMP test See CAMP TEST. reverse electron transport Energy-dependent (‘uphill’) electron flow along an ELECTRON TRANSPORT CHAIN (or part of an ETC); the energy for reverse electron transport is derived from proton motive force (see CHEMIOSMOSIS), and, in e.g. animal mitochondria, the electrons may derive from the oxidation of succinate. Reverse electron transport is an essential process in e.g. photosynthetic bacteria of the Rhodospirillineae; in these organisms, pmf derived from PHOTOSYNTHESIS is used not only for the synthesis of ATP but also for the generation of reducing equivalents by uphill electron flow to NAD+ . In Thiobacillus ferrooxidans, reduction of pyridine nucleotides is reported to involve uphill electron flow through the bc1 /NADH-Q oxidoreductase complex acting in reverse [JB (2000) 182 3602–3606]. reverse gyrase A TOPOISOMERASE which can introduce positive supercoiling into cccDNA, using the energy of ATP hydrolysis; the enzyme has been found e.g. in the archaean Sulfolobus acidocaldarius [Nature (1984) 309 669–681] and in bacteria of the order Thermotogales [JB (1991) 173 3921–3923] – all being thermophilic organisms. The function of reverse gyrase is unknown, but one suggestion is that it may have an important

the egg albumen, or in mammalian retroviruses by infection of the fetus via the placenta. Some authors regard this as a form of horizontal transmission, as distinct from the third route of transmission: vertical transmission by inheritance of the provirus through the germ line – i.e., the provirus is inherited as is any other chromosomal sequence. (cf. ENDOGENOUS RETROVIRUS and EXOGENOUS RETROVIRUS.) Genetic interactions. Retroviruses appear to be genetically unstable and give rise to defective and recombinant variants at high frequencies. For example, recombination may occur between the genomes of closely related retroviruses infecting the same cell. An intermediate in such recombination may be a heterozygous virus particle in which the two RNA ‘monomers’ are contributed by different viruses; recombination may result from a ‘copy-choice’ mechanism involving the transfer of nascent DNA strands from one template to another during reverse transcription. Recombination can also occur e.g. between the nucleic acid of an infecting exogenous retrovirus and that of an endogenous virus, or between retroviral and host nucleic acids. The mechanism for such recombination is unknown; it could occur by a copy-choice mechanism involving RNA transcripts of the relevant sequences, or by a breakage-and-reunion mechanism involving e.g. proviral DNA and chromosomal DNA. Recombination between retroviral and chromosomal sequences may lead to the incorporation of host genes into the viral genome. Such a recombinant viral genome is usually replication-defective since the cellular sequences are usually acquired at the expense of viral coding sequences. These viruses can thus replicate only in the presence of a replicationcompetent helper virus (i.e., one with intact gag, pol and env genes) which can provide the missing replication functions; the defective genome may then be packaged into particles (PSEUDOTYPES) which can infect other cells, thereby resulting in the transduction of cellular DNA to other host cells. Oncogenesis. The transducing ability of retroviruses was discovered when certain replication-competent viruses – which are normally capable of inducing neoplastic disease in their hosts only at very low frequencies and after long latent periods – were found to give rise to acutely oncogenic, usually replicationdefective variants; many of these variants were found to contain sequences derived from cellular ONCOGENES, and appear to have arisen by recombination between sequences of the infecting retrovirus and host c-onc sequences. The viral oncogenes (vonc) differ from their cellular counterparts e.g. in that they lack introns; they are subject to viral, rather than cellular, control signals, and appear to confer on the virus the ability to induce neoplastic disease efficiently and after a short latent period. (Not RETROVIRIDAE: Figure 2 (continued)

1. The ssRNA retroviral genome. 2. (−)-Strand DNA synthesis by reverse transcriptase is initiated on the tRNA primer at the (−) PBS, and (−)-strand DNA is synthesized to the 5′ end of the template. 3. The 5′ R region of the RNA template is removed by RNase H. The DNA R region can then pair with the RNA 3′ -R region, thus providing the template for continued DNA elongation. 4. As the (−) DNA strand elongates, the RNA template is degraded by RNase H; a short sequence of RNA at P [(+)PBS?], apparently being resistant to RNase H action, remains to function as a primer for the initiation of (+)-strand DNA synthesis [JV (1984) 52 314–319]. 5. (−)-Strand DNA synthesis reaches the end of the RNA template, thus providing a template for continued (+)-strand DNA synthesis. 6. (−)-Strand synthesis continues beyond the RNA genome length to duplicate the U3–R–U5 region. 7. Continued (+)-strand synthesis into the U3–R–U5 region results in the completed dsDNA molecule with a U3–R–U5 sequence (long terminal repeat, LTR) at each end.

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reverse mutation role in life at high temperatures. Possibly, the enzyme pre-dates the evolutionary split between archaeans and bacteria. reverse mutation Syn. BACK MUTATION. reverse passive latex agglutination test See LATEX PARTICLE TEST. reverse primer See FORWARD PRIMER. reverse transcriptase RNA-dependent (i.e. RNA-directed) DNA polymerase: an enzyme which synthesizes DNA on an RNA template. Reverse transcriptases are encoded by viruses of the RETROVIRIDAE, by RETROID VIRUSES, and by certain retroviruslike elements (e.g. A-TYPE PARTICLES and TY ELEMENTS); a reverse transcriptase has been isolated from the protozoan Paramecium tetraurelia [Eur. J. Biochem. (1987) 163 569–575], and genes encoding a reverse transcriptase have been demonstrated in certain myxobacteria and in Escherichia coli [Nature (1989) 339 254] (see also RETRON). (The DNA polymerase I of Escherichia coli has reverse transcriptase ability but, in this capacity, it has rather poor processivity [EMBO (1993) 12 387–396].) Like DNA-dependent DNA POLYMERASES, a reverse transcriptase requires a short RNA primer for the initiation of DNA synthesis, and catalyses polymerization in the 5′ -to-3′ direction; divalent cations (Mg2+ or Mn2+ ) are necessary for activity. The initial result of DNA synthesis on an RNA template (a process which is called reverse transcription or retrotranscription) is a DNA–RNA hybrid (see CDNA); at least some reverse transcriptases have RNase H activity (see RNASE H) and are able to degrade the RNA strand of the hybrid, allowing a complementary strand of DNA to be synthesized on the newly formed strand (giving rise to ds cDNA). Reverse transcriptases lack 3′ -to-5′ exonuclease activity, i.e. they have no proof-reading capacity (cf. DNA POLYMERASE), so that their synthesis of DNA is error-prone. These enzymes seem able to switch from one template to another during polymerization, possibly allowing recombination by a ‘copychoice’ mechanism (see RETROVIRIDAE). Reverse transcriptase can be inhibited e.g. by AZT, PHOSPHONOFORMATE and SURAMIN but is insensitive to many other inhibitors of DNA and RNA. Reverse transcriptases are employed in several techniques (e.g. REVERSE TRANSCRIPTASE PCR (rtPCR), NASBA) which are used for the in vitro amplification of nucleic acids. Commonly used enzymes include avian myeloblastosis virus reverse transcriptase (AMV reverse transcriptase) and Moloney murine leukaemia virus reverse transcriptase (MMLV reverse transcriptase). MMLV reverse transcriptase is a cloned enzyme of MWt ∼71000 which has RNase H activity. The AMV reverse transcriptase comprises two types of subunit: a (MWt 68000) and b (MWt 92000). The ab form has both DNA-dependent DNA polymerase and bidirectional RNase H activity (these two functions residing in the a subunit). [Example of use of AMV reverse transcriptase: JCM (1999) 37 524–530]. reverse transcriptase PCR (rtPCR, rt-PCR, RT-PCR; formerly: RNA PCR) A procedure in which (i) a strand of DNA is synthesized on an RNA target molecule by a REVERSE TRANSCRIPTASE – forming a hybrid RNA/DNA duplex; (ii) the strand of RNA is degraded, either by RNase H or by the RNase H activity of reverse transcriptase; (iii) a complementary strand of DNA is synthesized on the first strand, forming double-stranded cDNA; (iv) the dsDNA copy of the original RNA amplicon is amplified by standard PCR methodology. The initial phase (reverse transcription) may be carried out as a separate stage in a ‘two-tube’ approach [e.g. JVM (1997) 69 63–72]; alternatively,

both phases (reverse transcription and PCR proper) may be carried out in a single tube [e.g. JCM (1999) 37 524–530]. Reverse transcription, which requires a primer, is carried out isothermally at e.g. 50° C. Such relatively low temperatures can be problematic if the target RNA contains secondary structures that are destabilized only at a higher temperature: the presence of secondary structures can block the synthesis of cDNA by physically impeding the polymerase. The problem of secondary structures may be overcome by carrying out reverse transcription at a higher temperature. This approach requires a thermostable polymerase such as the rTth DNA polymerase (Perkin-Elmer) – a recombinant form of the Thermus thermophilus enzyme which can operate as a reverse transcriptase at 60–70° C in the presence of Mn2+ and can also amplify DNA in the cycling phase of PCR in the presence of Mg2+ . rtPCR can be used e.g. to detect specific types of mRNA molecule. It is particularly useful for studying RNA viruses; examples include: dengue virus [JCM (1999) 37 2543–2547]; hepatitis G virus [JCM (1997) 35 767–768]; hepatitis C virus and HIV-1 [Lancet (1999) 353 359–363]. reverse transcription See REVERSE TRANSCRIPTASE. reversion Restoration of the original phenotype of a mutant organism by means of a BACK MUTATION or a SUPPRESSOR MUTATION; the resulting organism is called a revertant. revertant See REVERSION. Reyes syndrome An acute disease of children and adolescents; it involves e.g. non-inflammatory encephalopathy with fatty infiltration and dysfunction of the liver, and is characterized clinically by persistent and profuse vomiting and neurological dysfunction – sometimes progressing to delirium, coma and death. The aetiology is unknown. The syndrome characteristically follows infection with certain viruses, particularly influenza A or B or varicella-zoster viruses. An association has also been recognized between the occurrence of Reyes syndrome and the administration of aspirin during the prodromal phase of the viral infection; in the USA, decreasing use of salicylates in children has apparently correlated with a decrease in the incidence of Reyes syndrome [Pediatrics (1986) 77 598–602]. RF Replicative form, an intermediate formed during the replication of certain ssDNA or ssRNA viral genomes; an RF is a double-stranded structure consisting of the viral strand basepaired with its (newly synthesized) complementary strand. (cf. RI.) In e.g. SSDNA PHAGES the RF is a circular dsDNA molecule; the supercoiled ccc form is designated RFI (cf. DNA I), while the relaxed form – nicked in one strand – is designated RFII (cf. DNA II). RF-1, RF-2, RF-3 See PROTEIN SYNTHESIS (termination). rfb gene See EHEC. RFLP Restriction fragment length polymorphism: a phrase which refers to differences in fragment length which may be obtained when related sequences of DNA are exposed to the same RESTRICTION ENDONUCLEASE(S); such differences may arise e.g. if sequence(s) have lost or gained one or more (relevant) restriction sites as a result of mutation, or if particular fragment(s) are longer or shorter, respectively, as a result of insertion or deletion of nucleotides. The concept of RFLP is illustrated in the figure. RFLP analysis is used e.g. for TYPING. For typing short sequences (e.g. a plasmid, viral DNA, or a short sequence in a bacterial chromosome), the fragments formed by restriction are examined by electrophoresis and staining (thus providing a fingerprint). This approach has been used e.g. for detecting variation in the genome of herpes simplex virus type 1 [RMM (1998) 9 217–224]. 660

Rhabdoviridae 1

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rh1 gene (rH1 gene) See PHASE VARIATION. rhabdocyst A rod-like EXTRUSOME which occurs in some gymnostome ciliates. Rhabdomonas See EUGLENOID FLAGELLATES. rhabdomyosarcoma See SARCOMA. rhabdos A type of (non-curved) CYTOPHARYNGEAL APPARATUS whose walls are strengthened externally by nematodesmata and are frequently lined by longitudinally arranged TRANSVERSE MICROTUBULES arising from peri-oral kinetosomes. Toxicysts are sometimes present. The rhabdos is believed to be more primitive than the CYRTOS. rhabdosarcoma See SARCOMA. Rhabdostyla See PERITRICHIA. Rhabdoviridae A family of enveloped, ssRNA-containing VIRUSes which can infect vertebrates, invertebrates or plants; the family includes some important pathogens, e.g. the causal agents of RABIES and VESICULAR STOMATITIS. The rhabdovirus virion contains 4–5 proteins designated L (large), G (glycoprotein), N (nucleocapsid), NS (non-structural) and M (matrix); 15–25% lipid (composition depending on host cell); and ca 3% carbohydrate. Genome: one molecule of linear negative-sense ssRNA (MWt ca. 3.5–4.6 × 106 ). Maturation involves budding through host membranes. Rhabdoviruses are stable at pH 5–10 (unstable at pH 3), but are rapidly inactivated by heating to 56° C, by UV and X-irradiation, and by lipid solvents. Animal rhabdoviruses are typically ‘bullet-shaped’ (i.e. cylindrical with one end flat, the other rounded), measuring e.g. ca. 170 × 70 nm (VSV). The virion consists of a helical nucleocapsid composed of an RNA-N protein complex, associated with proteins L and NS, and surrounded by protein M – the whole being enclosed within the lipoprotein (ether-sensitive) envelope. The G protein forms surface projections ca. 5–10 nm long; antibodies to the G protein neutralize the virus. Various enzymic activities are associated with the virion, including e.g. transcriptase, protein kinase, 5′ capping enzymes, etc. Virus replication occurs in the cytoplasm. Two genera: LYSSAVIRUS and VESICULOVIRUS. Other ‘probable members’ include e.g. BOVINE EPHEMERAL FEVER virus, EGTVED DISEASE virus, INFECTIOUS HAEMATOPOIETIC NECROSIS virus, red disease of pike virus, rhabdovirus of blue crab, rhabdovirus of Entamoeba, rhabdovirus of grass carp, SIGMA VIRUS of Drosophila, SPRING VIRAEMIA OF CARP virus. Plant rhabdoviruses are usually bacilliform, sometimes bulletshaped, typically ca. 200–350 × 70–95 nm; all contain proteins N and G, some have proteins L, M and NS, others have proteins ‘M1’ and ‘M2’. Each member generally infects only one or a few plant species, and is transmitted (circulatively) by one or more particular vectors (aphids, leaf-hoppers, plant-hoppers, bugs or mites); some members (not those infecting gramineous hosts) can be transmitted mechanically under experimental conditions. Two subgroups of plant rhabdoviruses (A and B) have been distinguished on the basis of the site of virus assembly, virion protein composition, and transcriptase activity in vitro. Members of subgroup A – e.g. lettuce necrotic yellows virus (type member), broccoli necrotic yellows virus, wheat striate mosaic virus – share some properties with Vesiculovirus: virions mature and accumulate in the host cell cytoplasm, contain protein M, and have readily detectable transcriptase activity in vitro. Members of subgroup B – e.g. potato yellow dwarf virus (type member), eggplant mottled dwarf virus – bud at the inner membrane of the nuclear envelope and accumulate in the perinuclear space, contain proteins M1 and M2, and have low transcriptase activity in vitro. Other probable (but ungrouped)

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RFLP (principle, diagrammatic). Horizontal lines represent related DNA duplexes. The top duplex has two sites for a given restriction endonuclease; enzymic cleavage (arrow) at each of these two sites produces three restriction fragments. In the centre duplex, the second cleavage site has been lost through mutation; enzymic cleavage produces only two fragments, fragment 1 being the same as before. The lower duplex contains an extra short sequence of nucleotides (dashed line); enzymic cleavage of this duplex produces three fragments, but fragment 2 is longer than that in the top duplex. Electrophoresis of the fragments from each duplex will produce different fingerprints.

RFLP-based typing proceeds differently when large sequences (e.g. a whole bacterial chromosome) are involved. Initially, chromosomes of the test strain are cleaved by restriction enzyme(s) and the fragments separated by electrophoresis in polyacrylamide gel. Bands of fragments in the gel are ‘blotted’ onto a membrane, and the membrane is then exposed to labelled probes complementary to a specific target sequence in the chromosome; thus, probes will hybridize only to those bands of fragments which include the target sequence, and only these bands will be made visible by the probe’s label. Suppose, for example, that the probe’s target is a sequence in a single-copy gene. In this case probes will hybridize to only one band of fragments on the membrane; however, this may be sufficient to reveal differences between test strains as the target-containing fragment may vary in length among the different strains (giving rise to bands in different relative positions in the gel). In some cases the probe is complementary to a multicopy target sequence; any target which occurs in multiple copies in the genome has the advantage that it will probably give rise to a fingerprint consisting of more than one band and (for this reason) is likely to have superior discriminatory power as a typing procedure. One example of this is IS6110 -based typing of Mycobacterium tuberculosis; most strains have multiple copies of IS6110 (strain H37Rv has 16 copies [Nature (1998) 393 537–544]), and, because IS6110 is a mobile genetic element, it can insert at different sites in the chromosome and (thus) give rise to new strains (with new fingerprints). Note that RIBOTYPING (q.v.) is a particular form of RFLP-based typing. A possible problem in RFLP-based typing arises because chromosomal DNA isolated from a test strain will have undergone modification (i.e. methylation of bases in certain sequences); such modification will inhibit certain restriction endonucleases so that a careful choice of enzymes is necessary. This problem can be avoided by amplifying a chromosomal target sequence in vitro by PCR; the amplicons (which lack methylation owing to synthesis in vitro) can then be used for RFLP analysis. PCRRFLP analysis has been used e.g. for typing isolates of Staphylococcus aureus from cows and sheep with mastitis [JCM (1999) 37 570–574]. RGD motif See INTEGRINS. 661

rhabdovirus rheumatoid arthritis A chronic, systemic disease involving inflammatory changes in the body’s connective tissues, resulting in a progressive, deforming ARTHRITIS. Pathogenesis appears to involve an autoimmune reaction (in genetically predisposed individuals) which is triggered by an unknown environmental factor (possibly a virus); IgM autoantibodies (‘rheumatoid factor’) to IgG are formed, and IgG–IgM immune complexes are deposited in the synovium and blood vessels, causing inflammation. Whether or not viruses have a role in the pathogenesis of rheumatoid arthritis is controversial, but parvovirus-like particles have been detected in synovial tissue from the joints of a rheumatoid arthritis patient [Science (1984) 223 1425–1428]. (See also ROSE–WAALER TEST.) rheumatoid factor See RHEUMATOID ARTHRITIS and ROSE–WAALER TEST. rhexolysis See CONIDIUM. rhinitis Inflammation of the nasal mucous membranes. It occurs e.g. in the COMMON COLD and in allergic reactions such as hay fever. Rhinocladiella See HYPHOMYCETES; see also CHROMOBLASTOMYCOSIS. rhinophycomycosis Nasofacial or rhinocerebral ZYGOMYCOSIS. rhinosporidiosis A chronic disease of man and animals, caused by Rhinosporidium seeberi, characterized by the formation of polyp-like growths chiefly on the mucosae of the nose and upper respiratory tract; breathing may be obstructed. Dissemination is rare. Rhinosporidium A genus of fungi of uncertain taxonomic position; R. seeberi, causal agent of RHINOSPORIDIOSIS, apparently resembles ‘Hyphochytridiomycetes’ rather than Chytridiomycetes [JMM (1985) 20 x (abstr.)]. In infected tissues, R. seeberi forms spherical sporangia (up to ca. 300 µm, depending e.g. on stage of development) which, when mature, develop thick refractile walls and undergo nuclear and cytoplasmic division to form numerous uninucleate endospores (6–7 µm); endospores are released on rupture of the cell wall. rhinotracheitis Inflammation of the mucous membranes of the nose and trachea. See e.g. FELINE RHINOTRACHEITIS and INFECTIOUS BOVINE RHINOTRACHEITIS. Rhinovirus A genus of viruses (family PICORNAVIRIDAE) which are acid-labile (being rapidly inactivated at pH < 6) and which infect the mammalian upper respiratory tract (cf. ENTEROVIRUS). Human rhinoviruses are the major causal agents of the COMMON COLD; many serotypes are known. They can be propagated in various human cell cultures (e.g. WI-38) and have an optimum growth temperature of 33° C. Most strains are stable at or below room temperatures and can withstand freezing; some strains are stable at 50° C for 1 hour. Most heat-labile serotypes (but not type 30) can be stabilized to heat by the presence of MgCl2 . Rhinoviruses can be inactivated by e.g. citric acid (see COMMON COLD), tincture of iodine or phenol/alcohol mixtures, but generally not by e.g. alcohols, bile salts, hexachlorophene, organic solvents, or quaternary ammonium compounds. [Clinical and epidemiological aspects: Book ref. 148, pp. 795–816. Nucleotide sequences of the genomes of human rhinovirus types 2 and 14: NAR (1985) 13 2111–2126 and PNAS (1985) 82 732–736, respectively.] Other members of the genus include the bovine rhinoviruses; ‘equine rhinoviruses’ may represent a separate genus. Rhipicephalus A genus of ixodid ticks which are vectors of certain diseases: e.g. REDWATER FEVER. Rhipidium See LEPTOMITALES. Rhipocephalus A genus of siphonaceous, calcified green seaweeds (division CHLOROPHYTA).

members of the plant rhabdoviruses include e.g. carrot latent virus, lucerne enation virus, raspberry vein chlorosis virus, and strawberry crinkle virus (all aphid-borne); barley yellow striate mosaic virus (= cereal striate virus), cereal chlorotic mottle virus, finger millet mosaic virus, maize mosaic virus, oat striate virus, rice transitory yellowing virus, Russian winter wheat mosaic virus, and wheat chlorotic streak virus (all hopper-borne); beet leaf curl virus (lace bug-borne); coffee ringspot virus (mite-borne). Listed by the ICTV [Book ref. 23, pp. 112–114] as ‘possible members’ are some non-enveloped viruses (e.g. Citrus leprosis virus and orchid fleck virus) and many virus-like particles; these appear to resemble rhabdovirus nucleocapsids (ca. 100–120 × 35 nm) and form characteristic ‘spoked-wheel’ structures in the plant cell nucleus. rhabdovirus A virus of the RHABDOVIRIDAE. rhamnogalacturonan See PECTINS. rhamnolipid (2-O-a-L-rhamnopyranosyl-a-L-rhamnopyranosyl-bhydroxydecanoyl-b-hydroxydecanoate) An extracellular glycolipid BIOSURFACTANT produced by certain strains of Pseudomonas aeruginosa during growth on HYDROCARBONS. L-rhamnose 6-Deoxy-L-mannose; it occurs e.g. in many plant glycosides and PECTINS, many streptococcal C SUBSTANCES, and some LIPOPOLYSACCHARIDES (e.g. the O-specific chains of certain Salmonella serotypes). Rhaphidophyceae See CHLOROMONADS. rhapidosomes Rod-shaped or tubular structures, 20–30 nm in diameter, which occur in many species of bacteria (e.g. Flexibacter, Pseudomonas spp) and cyanobacteria (e.g. Spirulina). Rhapidosomes (in different organisms) have been variously regarded as bacteriocins, defective phage tails, particles of mesosomal membrane, and cell components involved in motility. Rheinberg illumination (coloured field illumination; optical staining) Illumination analogous to that used in low-power darkfield MICROSCOPY (q.v.). Instead of an opaque stop, the condenser is fitted with a Rheinberg disc: a transparent disc with a central circular area of one colour and a surrounding annulus of one or more lighter colours; the central colour forms the background light while the specimen is lit by the peripheral rays of the lighter colour(s). rheotaxis A TAXIS in which the stimulus is a current; a positively rheotactic organism swims against a prevailing current (i.e., it swims ‘upstream’). rheotropism See TROPISM (sense 1). rheumatic fever A condition which occurs as a late complication of SCARLET FEVER or a group A streptococcal infection of the throat (‘strep throat’, tonsillitis) or middle ear (OTITIS MEDIA); it may follow an asymptomatic streptococcal infection, but rarely or never occurs after streptococcal skin infection (e.g. IMPETIGO, ERYSIPELAS) – cf. POST-STREPTOCOCCAL GLOMERULONEPHRITIS. Rheumatic fever occurs most commonly in children aged between 5 and 15. An asymptomatic latent period of 1–3 weeks may occur between the original infection and the onset of rheumatic fever. Onset is usually rather insidious, with malaise, fever, and inflammation of joints; other symptoms may include e.g. subcutaneous nodules, rash, and/or involuntary twitching movements (Sydenham’s chorea, ‘St Vitus’s dance’). Endocarditis may develop and may lead to chronic rheumatic valvular heart disease. An individual who has suffered an attack of rheumatic fever has greatly increased susceptibility to subsequent streptococcal infection. Rheumatic fever is apparently unrelated to the presence of living streptococci and is believed to be caused by an immunopathological mechanism; it may be due to an autoimmune reaction between anti-group A streptococcal antibody and a host tissue component. 662

Rhizosolenia rhizogenic Capable of inducing root formation. rhizoid A root-like structure which forms part of the thallus in certain algae and fungi; it may anchor the organism to the substratum and/or act as an absorptive organ or organelle. (cf. RHIZOMYCELIUM.) rhizomania See BEET NECROTIC YELLOW VEIN VIRUS. rhizomorph (mycol.) A macroscopic, typically dark-coloured thread of hard, compacted tissue formed by certain higher fungi, e.g. Armillaria mellea; the tissue generally appears to consist of individual cells rather than hyphae. Rhizomorphs are enduring structures which can remain dormant under adverse conditions and which can enable a fungus to spread into the surrounding environment – e.g. those of A. mellea permit the fungus to spread from an infected tree to an uninfected tree via the soil. (See also DRY ROT.) Rhizomucor A genus of fungi of the MUCORALES. R. pusillus (formerly Mucor pusillus) can cause ZYGOMYCOSIS. (See also COMPOSTING.) R. miehei (formerly Mucor miehei ) and R. pusillus form PROTEASES which are used as rennin substitutes. rhizomycelium (mycol.) Branching, anucleate or sparsely nucleate, rhizoidal filaments of variable width which form part of the thallus e.g. of Nowakowskiella and of some species of the Laboulbeniales. Rhizophidium See RHIZOPHYDIUM. Rhizophydium (Rhizophidium) A genus of eucarpic fungi (order CHYTRIDIALES) which occur as saprotrophs or as parasites of aquatic or terrestrial plants; R. graminis parasitizes the root cells of mono- and dicotyledonous plants (apparently without causing them harm), while R. couchii has been reported to parasitize Spirogyra. In the asexual cycle of R. couchii, a zoospore encysts on the surface of a host and gives rise to a thallus whose rhizoids penetrate the host; the extracellular part of the thallus subsequently becomes converted into a zoosporangium. In the sexual cycle, zoospores develop into extracellular, rhizoidbearing gametangia; after plasmogamy (and karyogamy?) the zygote becomes a thick-walled resting zoosporangium. rhizoplane The root surface – cf. RHIZOSPHERE. rhizoplasmodium See LABYRINTHULAS. rhizopod An organism of the RHIZOPODA. Rhizopoda A superclass of protozoa (subphylum SARCODINA) which are motile by means of lobopodia, filopodia or reticulopodia (see PSEUDOPODIUM) or by flow of protoplasm without the formation of discrete pseudopodia. Classes: ACARPOMYXEA; Acrasea (see ACRASIOMYCETES); EUMYCETOZOEA; FILOSEA; GRANULORETICULOSEA; LOBOSEA; Plasmodiophorea (= PLASMODIOPHOROMYCETES); XENOPHYOPHOREA. rhizopodium See PSEUDOPODIUM. Rhizopogon See GASTEROMYCETES (Hymenogastrales). Rhizopus A genus of fungi (order MUCORALES) which occur on soil, fruit etc. The organisms form a branched, aseptate mycelium. R. nigricans (= R. stolonifer) can attach to the substratum by means of branching rhizoids; a stolon (a surface hypha analogous to the stolons in higher plants) grows for some distance and then gives rise to more rhizoids and to one or more vertical sporangiophores. The organisms form ZYGOSPORES (see also COMPATIBILITY sense 2). Rhizopus spp are used commercially e.g. in the preparation of ONCOM, RAGI and TEMPEH and in certain STEROID BIOCONVERSIONS. (See also BREAD SPOILAGE and ZYGOMYCOSIS.) Rhizosolenia A genus of freshwater and marine centric DIATOMS. Some (marine) species contain a nitrogen-fixing cyanobacterial symbiont, Richelia intracellularis, which occurs as short, Calothrix-like filaments – each with a heterocyst at one end or,

Rhizamoeba See ACARPOMYXEA. Rhizidiomyces A genus of unicellular fungi (class HYPHOCHYTRIOMYCETES) which occur in soil and as parasites of certain water moulds (members of the Saprolegniaceae) and algae (e.g. Vaucheria). Rhizidiomycetaceae See HYPHOCHYTRIOMYCETES. rhizine (rhizina) (lichenol.) A root-like structure consisting of a compact bundle of hyphae. Rhizines (rhizinae) arise mainly from the lower surface of the (usually foliose) thallus and serve to anchor the thallus to the substratum; in some species they may also facilitate the uptake of water and nutrients by the thallus [Bryol. (1981) 84 1–15]. Rhizines may be unbranched or may be sparsely or extensively branched – branching being e.g. ‘squarrose’ (short branchlets emerging at ca. 90° ) or dichotomous. Rhizobiacea A family of Gram-negative, asporogenous, rodshaped, motile, aerobic, chemoorganotrophic bacteria; all (except Agrobacterium radiobacter ) can induce tumour-like growths in plants. Genera: AGROBACTERIUM, BRADYRHIZOBIUM, PHYLLOBACTERIUM, RHIZOBIUM. Rhizobium A genus of Gram-negative bacteria of the RHIZOBIACEAE. Cells: rods, 0.5–0.9 × 1.2–3.0 µm; pleomorphic under adverse conditions. Motile: one (usually subpolar) flagellum (in R. loti ) or several lateral or sometimes polar flagella (in R. leguminosarum and R. meliloti ); in some strains ‘complex flagella’ occur: see FLAGELLUM. Refractile PHB granules are common, especially in older cells. Colonies: mucilaginous, usually 2–4 mm diameter in 3–5 days on yeast extract–manitol–mineral salts agar (cf. BRADYRHIZOBIUM). Acid (no gas) is formed from a range of carbohydrates (e.g. mannitol). Abundant extracellular slime (including a neutral (1 → 2)-bglucan) is produced in carbohydrate-containing media. [Media and methods: Book ref. 45, pp. 824–834.] GC%: 59–64. Type species: R. leguminosarum. Rhizobium spp are common in soil [ecology: Book ref. 45, pp. 818–822] and can incite ROOT NODULE formation in certain leguminous plants (mainly in temperate regions – cf. STEM NODULES); the free-living organisms appear to be incapable of nitrogen fixation. Strains which are both infective (able to induce nodule formation) and effective (able to fix nitrogen) tend to become ineffective (but may remain infective) e.g. after continual laboratory cultivation. R. phaseoli, R. trifolii and R. viceae are currently regarded as biotypes of R. leguminosarum. R. lupini is currently not a recognized species; it may be a species or biotype of Bradyrhizobium. R. japonicum: see BRADYRHIZOBIUM. [Book ref. 22, pp. 235–242.] Rhizocarpon A genus of LICHENS (order LECANIDIALES); photobiont: a green alga. The thallus is crustose, typically forming a mosaic of yellow or grey areolae between which the black hypothallus is visible. Saxicolous. Apothecia: black, lecideine; ascospores: septate to muriform. [Ascus structure: Lichenol. (1980) 12 157–172.] Rhizoclonium A genus of filamentous, siphonocladous green algae (division CHLOROPHYTA) in which the filaments are unbranched or bear laterally inserted rhizoidal branches. Rhizoctonia A genus of fungi (order AGONOMYCETALES) which include some important plant pathogens. R. leguminicola, the causal agent of blackpatch disease of clover (see SLAFRAMINE), can form sclerotia under appropriate conditions. R. solani can cause DAMPING OFF and EYESPOT (sense 2). (See also FOOT-ROT sense 2.) [Systematics and phylogeny of the Rhizoctonia complex: Bot. Gaz. (1978) 139 454–466; genetics and pathology of R. solani : ARPpath. (1982) 20 329–347.] 663

rhizosphere in the dividing diatom, at both ends. The association is not obligatory, and Richelia may also be found free-living or as an epiphyte on diatoms of the genera Chaetoceros, Hemiaulus and Rhizosolenia. (cf. RHOPALODIA.) rhizosphere An environment regarded, variously, as e.g. (a) that region of the soil which is modified as a result of the uptake and deposition of substances by a growing root [AEE (1985) 12 99–116]; (b) the root itself, together with that volume of soil which it influences [Book ref. 112, p. 237]; or (c) the root surface (rhizoplane) together with that region of the surrounding soil in which the microbial population is affected, qualitatively and/or quantitatively, by the presence of a root. The rhizosphere may extend a few millimetres, or centimetres, from the rhizoplane. From a growing root, a number of substances pass out into the soil. These substances include various carbohydrates (see also MUCIGEL), vitamins, amino acids and sugars – many of which serve as nutrients and/or as sources of energy for microorganisms. Presumably as a result of this, the microflora of the rhizosphere differs appreciably from that of the surrounding soil. In the rhizosphere, bacterial numbers are often 10- to 50-fold higher than they are in the surrounding soil; the bacteria are mainly Gram-negative rods (e.g. pseudomonads), Gram-positive bacteria typically being less numerous than they are outside the rhizosphere. It has been reported that the presence of a vesicular-arbuscular MYCORRHIZA (involving Glomus fasciculatum) reduces the proportion of fluorescent pseudomonads and increases the proportion of facultatively anaerobic bacteria in the rhizosphere – but does not affect the absolute number of Gram-negative bacteria [SBB (1986) 18 191–196]. Numerically, fungi may be present in similar or slightly greater abundance in the rhizosphere as compared with the surrounding soil. However, there may be qualitative (species) differences between rhizosphere and non-rhizosphere fungi, and in at least some cases there is evidence that the rhizospheres of certain plants encourage, or select, particular fungi. The extent to which the plant benefits from the rhizosphere microflora remains unclear. It seems possible that the microflora may play some part in protecting the plant from the incursions of soil-borne pathogens; additionally, the plant may benefit from the mineralizing activities of these organisms, and it is generally believed that the presence of the rhizosphere microflora promotes the uptake of minerals (e.g. phosphate) by the root. rhizothamnium A Myrica-type ACTINORRHIZA. rhl genes See QUORUM SENSING. rho factor (r factor) See TRANSCRIPTION. rho-form See MYCOPLASMA (M. mycoides). rho gene In e.g. Escherichia coli : the gene encoding the r factor (see TRANSCRIPTION). rho− petite See PETITE MUTANT. rho0 petite See PETITE MUTANT. rhodamine A generic term for a group of substituted xanthene FLUOROCHROME dyes; examples: rhodamine B (fluorescence red – see also AURAMINE–RHODAMINE STAIN and LISSAMINE RHODAMINE), rhodamine S (fluorescence yellow), rhodamine O (red), rhodamine 3G (orange). The rhodamines include cationic, anionic and neutral dyes. Uptake of cationic rhodamines (e.g. rhodamine 123) appears to depend on membrane potential in viable, functioning mitochondria [JCB (1981) 88 526–535] and bacteria [FEMS (1984) 21 153–157]. (See also VITAL STAINING.) rhodanese (thiosulphate sulphurtransferase; EC 2.8.1.1) An enzyme that catalyses e.g. the formation of thiocyanate (SCN− ) and sulphite (SO3 2− ) from THIOSULPHATE and cyanide; it

occurs e.g. in certain bacteria (including Bacillus subtilis, Desulfotomaculum nigrificans, Thiobacillus spp), in plants, and in most mammalian tissues. It has been suggested that one of the roles of rhodanese is to donate sulphur to a thiophilic anion (e.g. dihydrolipoate) which can complex iron and promote the formation of IRON–SULPHUR PROTEINS [TIBS (1986) 11 369–372; discussion: TIBS (1987) 12 56–57]. Rhodobacter A proposed genus of bacteria [IJSB (1984) 34 340–343] which includes species transferred from RHODOPSEUDOMONAS (q.v.) and re-designated Rhodobacter adriaticus, R. capsulatus (type species), R. sphaeroides and R. sulfidophilus. The genus includes motile and non-motile organisms; the cells divide by binary fission. Rhodochaete See RHODOPHYTA. rhodocladonic acid A bright-red naphthoquinone pigment found in the hymenial discs of certain CLADONIA spp. Rhodococcus A genus of aerobic, chemoorganotrophic, nonmotile bacteria (order ACTINOMYCETALES, wall type IV) which occur e.g. in soil, in aquatic habitats, and as pathogens of man and other animals. In culture, the cells of all species are cocci, or coccobacilli, which – depending on species – give rise e.g. to pleomorphic rods or to a branching mycelium; the rods or mycelium subsequently fragment to form the next generation of coccoid forms. Acid-fastness appears to be variable. The cell wall contains MYCOLIC ACIDS. The organisms grow well on nutrient media at 30° C; some strains need thiamine. Colonies are often pigmented (e.g. yellow, orange, red). Glucose is metabolized oxidatively. GC%: ca. 63–73. Type species: R. rhodochrous. The genus includes R. bronchialis; R. coprophilus (a mycelial species); R. equi (formerly Corynebacterium equi : a non-mycelial species which is the causal agent of e.g. suppurative bronchopneumonia in the horse); R. erythropolis; R. fascians (formerly Corynebacterium fascians [SAAM (1984) 5 225–229]); R. globerulus; R. luteus; R. maris; R. rhodnii ; R. rhodochrous (a species which forms branching rods, but not mycelium); R. ruber (a mycelial species); R. rubropertinctus; and R. terrae. [Book ref. 73, p. 93.] [A marine species, R. marinonascens: IJSB (1984) 34 127–138.] (See also CORYNECINS.) Rhodocyclus A proposed genus of non-motile, spiral-shaped photosynthetic bacteria (family RHODOSPIRILLACEAE) consisting of a single species, R. purpureus [IJSB (1978) 28 283–288]. It was later proposed that certain species be transferred from the genera RHODOPSEUDOMONAS (q.v.) and RHODOSPIRILLUM (q.v.) and re-designated Rhodocyclus gelatinosus and R. tenuis, respectively [IJSB (1984) 34 340–343]. Rhodomicrobium A genus of photosynthetic bacteria (class RHODOSPIRILLACEAE); the sole species, R. vannielii, occurs e.g. in freshwater muds and in estuarine and marine habitats. R. vannielii contains Bchl a and carotenoids (mainly b-carotene and spirilloxanthin) in lamellar intracytoplasmic membrane systems; cell suspensions are typically pink-brown. Growth occurs photoorganotrophically under anaerobic conditions, or chemoorganotrophically under microaerobic to aerobic conditions in the dark. R. vannielii undergoes one of two types of vegetative cell cycle, depending on growth conditions. In one type, a nonmotile, ovoid cell (ca. 1–3 µm) becomes prosthecate, and a daughter cell is formed by budding at the tip of the PROSTHECA. The daughter cell remains attached, forms a prostheca at the opposite pole, and buds in turn. This leads eventually to an array of cells which are joined together by branched and unbranched filaments (ca. 0.3 µm wide) derived from the 664

Rhodospirillaceae prosthecae. (Branches arise from the filaments.) Each cell is separated from its neighbour by a plug formed within the filament joining them. Such arrays – apparently the commonest form under natural conditions – may be produced under conditions of high light intensity and low concentrations of CO2 . If the light dims and CO2 levels rise (e.g. as the array becomes large), motile (peritrichous) swarmer cells form at the ends of filaments and are released by binary fission; under suitable conditions swarmers shed their flagella and become non-motile prosthecate cells, thus completing the cycle. If conditions of low light and high CO2 persist, a second (‘simplified’) cell cycle occurs: arrays are not formed – budding cells giving rise only to swarmers; array formation can subsequently occur if CO2 concentration decreases and light intensity increases. Under starvation conditions, cell arrays give rise to exospores: angular structures, resistant to heat and drying, which form at the tips of filaments and are released by binary fission; the exospores can germinate under aerobic conditions in the dark or anaerobically in the light, forming up to four vegetative cells. (Exospores are not formed in the ‘simplified’ cycle; late exponential phase cultures contain ‘tiny’ cells which are not resistant to stress [JGM (1980) 117 47–55].) [Reviews: ARM (1981) 35 567–594; Book ref. 28, pp. 188– 210.] (See also HYPHOMICROBIUM.) rhodomycin See ANTHRACYCLINE ANTIBIOTICS. Rhodophyceae See RHODOPHYTA. Rhodophyta (red algae) A division of ALGAE. Over 95% of the ca. 5000 species of red algae are marine organisms; those which occur in freshwater and/or soil habitats include species of Audouinella, Bangia, Batrachospermum, Chroodactylon, Hildenbrandia, Lemanea and Porphyridium. (Some genera, e.g. Bangia, Bostrychia and Hildenbrandia, contain both marine species and freshwater species.) A few red algae are parasitic on other algae (see e.g. CHOREOCOLAX and HOLMSELLA). In most red algae the thallus is a branched filament or ribbon. However, some species are sheet-like (e.g. Porphyra) or crust-like (e.g. Lithophyllum), while a few (e.g. PORPHYRIDIUM) are unicellular. Some red algae are calcified – e.g. Corallina spp (thalli: erect, articulated) and Lithophyllum. Multicellular thalli (which are commonly 5–50 cm in length) are typically attached to rocks etc by a holdfast. The CELL WALL may contain cellulose or xylans. Plasmodesmata appear to be absent, but many multicellular red algae contain PIT CONNECTIONS. There are no flagellated species, and flagellated gametes are not produced. Marine species are usually some shade of red, while freshwater species are typically blue-green, yellow-green, brown or grey. Red algae contain CHLOROPHYLL a, and some also contain chlorophyll d ; the THYLAKOIDS occur singly (i.e., unassociated) and bear PHYCOBILISOMES containing phycoerythrins and/or phycocyanins. Various CAROTENOIDS (e.g. xanthophylls and b-carotene) are usually present. Storage products include FLORIDEAN STARCH and FLORIDOSIDE (see also ISOFLORIDOSIDE). Sexual reproduction occurs in most species (but apparently not in Porphyridium) and oogamy is common; life cycles are often complex. Certain red algae are used as sources of AGAR and CARRAGEENAN, while some are used as food (see e.g. LAVER, NUNGHAM, PALMARIA). All species are placed in one class: Rhodophyceae. Orders [Book ref. 130]: Bangiales (e.g. Bangia, PORPHYRA);

Ceramiales (e.g. Bostrychia; Ceramium, Griffithsia, Polysiphonia); Compsopogonales (e.g. Compsopogon); Cryptonemiales (e.g. CHOREOCOLAX, Corallina, Gloiopeltis, Hildenbrandia, HOLMSELLA, Lithophyllum); Gigartinales (e.g. Chondrococcus, Chondrus, Eucheuma, Furcellaria, Gardneriella, GIGARTINA, Gracilaria, Iridaea); Nemalionales (e.g. Audouinella, Batrachospermum, Gelidium, Lemanea); Palmariales (e.g. Palmaria); Porphyridiales (e.g. Chroodactylon, Cyanidium, PORPHYRIDIUM); Rhodochaetales (e.g. Rhodochaete); Rhodymeniales (e.g. Coeloseira, Rhodymenia). [Biology of freshwater red algae: Book ref. 167, pp. 89–157.] Rhodopila A proposed genus of bacteria [IJSB (1984) 34 340–343] which includes a species transferred from RHODOPSEUDOMONAS (q.v.) and re-designated Rhodopila globiformis; the coccoid, flagellated cells of R. globiformis grow only at low pH. Rhodopseudomonas A genus of photosynthetic bacteria (family RHODOSPIRILLACEAE). Cells: flagellated (or non-motile) rods or cocci, typically 1–5 µm; most species contain Bchl a, R. sulfoviridis and R. viridis contain Bchl b. R. acidophila, R. palustris (the type species), R. sulfoviridis and R. viridis divide by budding; other species divide by binary fission. R. palustris and R. viridis form prosthecae. The oval to rodshaped species R. adriatica, R. capsulata, R. sphaeroides and R. sulfidophila all have vesicular-type photosynthetic membranes, and it has been proposed that they be transferred to a new genus: RHODOBACTER; it has also been proposed that the coccoid species R. globiformis (which has a vesicular photosynthetic membrane) and the curved, rod-shaped species R. gelatinosa be transferred to the genera RHODOPILA and RHODOCYCLUS, respectively [IJSB (1984) 34 340–343]. [Gene transfer mechanisms: Ann. Mic. (1983) 134 B 195– 204.] (See also CAPSDUCTION.) Rhodospirillaceae (purple non-sulphur bacteria, or non-sulphur purple bacteria; Athiorhodaceae) A heterogeneous family (see RHODOSPIRILLALES) of photosynthetic bacteria (suborder RHODOSPIRILLINEAE); they occur typically in those anaerobic habitats in which a range of simple organic substrates has been made available by the metabolic activities of chemoorganotrophic bacteria – e.g. in the mud of ponds and rivers, and in sewage lagoons. The organisms occur in freshwater, brackish and marine habitats and in moist soils. Most species contain only Bchl a (two species of Rhodopseudomonas have only Bchl b) – see CHLOROPHYLLS; these pigments, and various carotenoids, occur in lamellar, tubular or vesicular intracytoplasmic membrane systems, according to species. The organisms include cocci, rods and spiral forms; most species divide by binary fission, but several divide by budding (see e.g. RHODOPSEUDOMONAS). Heat-resistant forms are produced by Rhodomicrobium vannielii. Most species (not e.g. Rhodocyclus purpureus) exhibit flagellar motility. Gas vacuoles are absent. The organisms are primarily photoorganotrophic heterotrophs under anaerobic conditions, but a few species, e.g. Rhodopseudomonas sulfidophila, can grow as photolithotrophic autotrophs (using sulphide as electron donor), and some other members of the family can use sulphide as electron donor only when it is present in low concentrations. It has been shown that at least some species can oxidize elemental sulphur [JGM (1985) 131 791–798]; sulphide (or thiosulphate) can be oxidized to sulphate (without sulphur formation) by e.g. Rhodopseudomonas sulfidophila. Many species can oxidize sulphide with the production of extracellular deposits of sulphur. A number of species can use hydrogen as an electron donor for 665

Rhodospirillales photolithotrophic growth. Typically, growth requires one or more factors such as biotin, p-aminobenzoic acid and thiamine; many species can carry out nitrogen fixation, but a good rate of growth generally requires a source of organic nitrogen. Under aerobic or microaerobic conditions most species are chemoorganotrophic. Genera: RHODOMICROBIUM, RHODOPSEUDOMONAS, RHODOSPIRILLUM (the type genus); see also RHODOBACTER, RHODOCYCLUS, RHODOPILA. Rhodospirillales An order of Gram-negative anoxygenic photosynthetic bacteria (cf. CYANOBACTERIA). All species can carry out anoxygenic PHOTOSYNTHESIS under anaerobic conditions, but some (e.g. Chloroflexus aurantiacus, Thiocapsa roseopersicina, most members of the Rhodospirillaceae) can also grow chemoorganotrophically under aerobic or microaerobic conditions. All species contain one or more bacterioCHLOROPHYLLS and CAROTENOIDS; maximum concentrations of the pigments occur only under anaerobic conditions in low levels of light. (cf. ERYTHROBACTER.) The order includes cocci, rods, filaments and spiral forms; motile species may have flagella or may exhibit GLIDING MOTILITY. Endospores are not formed. In most species cell division occurs by binary fission; Pelodictyon clathratiforme can divide by ternary fission, and BUDDING occurs in some species of Rhodopseudomonas and in Rhodomicrobium vannielii. Many species can carry out NITROGEN FIXATION. Suborders: CHLOROBIINEAE and RHODOSPIRILLINEAE. The order appears to be taxonomically unsound; thus, e.g. not only is there a wide divergence between the two suborders, but some members of the family Rhodospirillaceae seem to be more closely related to certain non-photosynthetic bacteria than to other members of the family. (See also CHLOROBIINEAE.) (See also HELIOBACTERIUM.) Rhodospirillineae (purple bacteria) A suborder of photosynthetic bacteria (order RHODOSPIRILLALES); species contain bacteriochlorophyll a (usually) or b (in a few cases) in intracellular membrane systems that are continuous with the cytoplasmic membrane (cf. CHLOROBIINEAE). Most species are motile (flagellate). The suborder includes metabolically diverse species; CO2 fixation occurs mainly via the CALVIN CYCLE. Families: CHROMATIACEAE and RHODOSPIRILLACEAE. Rhodospirillum A genus of photosynthetic bacteria (family RHODOSPIRILLACEAE). Cells: spiral-shaped, polarly flagellated, 3–10 µm long and 0.5–1.5 µm wide; they contain vesicular, lamellar or stacked photosynthetic membranes. The cells divide by binary fission. Species: R. fulvum, R. molischianum, R. photometricum, R. rubrum (type species), and R. salexigens; it has been proposed that R. tenue be transferred to the genus RHODOCYCLUS [IJSB (1984) 34 340–343]. Rhodospirillum haem protein See RHP. Rhodosporidium See SPORIDIALES and RHODOTORULA. Rhodotorula A genus of imperfect yeasts (class HYPHOMYCETES). The cells are spheroidal, ovoid or elongate; vegetative reproduction occurs by multilateral budding. Pseudomycelium and true mycelium may be formed by some strains of some species. Ballistospores are not produced. Visible carotenoid pigments are synthesized by cultures on e.g. malt agar; the colonies are typically red, pink, orange or yellow, and may be mucoid (capsulated strains), pasty, or dry and wrinkled. Metabolism is strictly respiratory; inositol is not assimilated. NO3 − is assimilated by all species except R. minuta and R. rubra. Other species include e.g. R. aurantiaca, R. glutinis (a complex of anamorphs of at least three teleomorphic species: Rhodosporidium diobovatum, Rhodosporidium sphaerocarpum and Rhodosporidium toruloides) and R. graminis. Strains have been isolated from e.g. plants and

plant debris, beverages, pickling brines (see also SAUERKRAUT), seawater, fresh water, etc. [Book ref. 100, pp. 893–905.] Rhodymenia See RHODOPHYTA (cf. PALMARIA). Rhopalodia A genus of pennate DIATOMS. The freshwater species R. gibba and R. gibberula contain, in addition to the typical diatom chloroplast, intracellular inclusion bodies which closely resemble thin-walled unicellular cyanobacteria and which carry out light-dependent nitrogen fixation. (cf. RHIZOSOLENIA.) Rhopalomyces See ZOOPAGALES. rhoptries (sing. rhoptry) In members of the APICOMPLEXA: elongate (e.g. club-shaped) osmiophilic organelles found at the anterior end of the cell; two such organelles per cell occur e.g. in the merozoites of Isospora spp and many Eimeria spp, while more than two per cell occur e.g. in some Eimeria merozoites and in Sarcocystis and Toxoplasma. Rhoptries appear to secrete enzymes which assist in host cell penetration [JUR (1983) 83 85–98]. RHP (Rhodospirillum haem protein; cytochromoid c) Original name for CYTOCHROMES c′ and cc′ which occur in at least some purple phototrophic bacteria and in Pseudomonas denitrificans. Rhynchodida See HYPOSTOMATIA. Rhynchoidomonas A genus of monoxenous protozoa (family TRYPANOSOMATIDAE) parasitic in the gut (particularly the Malpighian tubules) of flies. The organisms, 10–50 µm long, occur in the trypomastigote form but lack a free flagellum. Rhynchomonas See BODONINA. rhynchosporium A plant disease caused by Rhynchosporium sp: see e.g. LEAF BLOTCH. Rhynchosporium See HYPHOMYCETES; see also LEAF BLOTCH. Rhytidhysteron See ASCOSTROMA. Rhytisma A genus of fungi of the RHYTISMATALES. R. acerinum causes tar spot disease in Acer spp (e.g. maple): conspicuous, flat, roundish, black stromata (ca. 1–2 cm diam.) develop on the upper surfaces of leaves from mid-summer onwards, the stromata bearing conidiophores of the imperfect (Melasmia) stage during the autumn; ascocarps (the over-wintering stage) develop within the stromata, each stroma splitting radially in the spring to expose the apothecial hymenia of asci containing filiform ascospores. Rhytismatales An order of fungi (subdivision ASCOMYCOTINA) which include saprotrophic and plant-parasitic species. Ascocarp: APOTHECIOID, immersed in a stroma or in host tissue; hamathecium: filiform paraphyses. Asci: unitunicate; sometimes stipitate. Ascospores: septate or aseptate. Genera: e.g. Coccomyces, Hypoderma, RHYTISMA. RI Replicative intermediate, an intermediate formed during the replication of certain ssRNA viral genomes; an RI is a partially double-stranded structure with many (growing) single-stranded ‘tails’ formed as a result of the concomitant synthesis of many new RNA strands on the same RNA template strand. (cf. RF.) Ri plasmid See HAIRY ROOT. RIA RADIOIMMUNOASSAY. RIBA See HEPATITIS C. ribavirin (1-b-D-ribofuranosyl-1,2,4-triazole-3-carboxamide; Virazole) An ANTIVIRAL AGENT which is active against a wide range of viruses and which has been used therapeutically against infections caused e.g. by the hepatitis C, Lassa fever and SARS (coronavirus) viruses. Ribavirin is phosphorylated in cells; the monophosphate inhibits IMP dehydrogenase (and hence GMP and GTP synthesis: see Appendix V(a)), while the triphosphate directly inhibits e.g. influenzavirus RNA-dependent RNA polymerase. A suggestion that ribavirin may act as a cap analogue (see MRNA (b)) was not confirmed [RNA (2005) 11 1238–1244]. 666

ribosome Analogues and derivatives of ribavirin include e.g. ribavirin 2′ , 3′ , 5′ -triacetate (RTA) and selenazofurin (= selenazole, 2b-D-ribofuranosylselenazole-4-carboxamide), both of which are apparently more effective than ribavirin itself. Ribi cell fractionator An apparatus similar in principle to the FRENCH PRESS but capable of higher pressures. ribitol (adonitol) An optically inactive PENTITOL formed e.g. by the reduction of RIBOSE; it is a component of e.g. RIBOFLAVIN and some TEICHOIC ACIDS, and is a major product of photosynthesis in certain green algae (e.g. Coccomyxa, Myrmecia, Trentepohlia). (See also HONEYDEW and Appendix III(d).) riboflavin (riboflavine; vitamin B2 ; lactoflavin) A water-soluble, photolabile, heat-stable VITAMIN: 6,7-dimethy;-9-(1′ -D-ribityl)isoalloxazine. The important coenzyme forms are riboflavin 5′ phosphate (= flavin mononucleotide, FMN) and flavin adenine dinucleotide (FAD) – see figure; these are the prosthetic groups of flavoproteins: proteins which act as hydrogen-carriers in a wide range of redox reactions. The hydrogen atoms are carried at the N1 and N10 positions of the isoalloxazine ring. Some reduced flavoproteins may be re-oxidized directly by molecular oxygen, HYDROGEN PEROXIDE being a product; others may be reoxidized via an ELECTRON TRANSPORT CHAIN. Riboflavin may act as a photoreceptor in the phototropic responses of certain fungi; FMN is involved in bacterial BIOLUMINESCENCE. Most microorganisms can apparently synthesize riboflavin, but it is required as a growth factor e.g. by Lactobacillus spp, Crithidia fasciculata and Tetrahymena spp. Under certain cultural conditions some organisms (e.g. Ashbya gossypii, Eremothecium ashbyii, certain yeasts, Clostridium spp) secrete large quantities of riboflavin into the medium; A. gossypii and E. ashbyii are important commercial sources of the vitamin. ribonuclease See RNASE. ribonucleic acid See RNA. ribonucleoside See NUCLEOSIDE. ribonucleotide See NUCLEOTIDE. ribonucleotide reductase See NUCLEOTIDE. (See also IRON.) ribophage A BACTERIOPHAGE with an RNA genome. ribophorins Glycoproteins which, in eukaryotes, appear to play a role in binding RIBOSOMES to the rough ENDOPLASMIC RETICULUM.

RiboPrinter An automated system (manufactured by Qualicon, Wilmington, DE, USA) designed for rapidly characterizing a bacterium to strain level on the basis of its ribotype. The apparatus is intended primarily for use in the food industry, and its database contains ribotype patterns of hundreds of strains of food-borne pathogens (with which the ribotypes of new isolates can be compared). [Comparison of the RiboPrinter with traditional ribotyping: LAM (1999) 28 327–333.] [Use of automated riboprinter and PFGE for epidemiological studies of Haemophilus influenzae in Taiwan: JMM (2001) 50 277–283.] ribose An aldopentose (see PENTOSES) which plays many important roles in cell structure and metabolism. Phosphorylated derivatives of ribose and 2-deoxyribose are components of NUCLEOTIDES and NUCLEIC ACIDS [see also Appendix V(a) and (b)], and ribose phosphates are important intermediates in certain metabolic pathways: e.g. CALVIN CYCLE, HEXOSE MONOPHOSPHATE PATHWAY [Appendix I(b)], biosynthesis of phenylalanine, tyrosine and tryptophan [Appendix IV(f)] and of histidine [Appendix IV(g)], etc. [See also Appendix III(d).] ribose phosphate pathway Syn. RMP PATHWAY. ribosome A ribonucleoprotein intracellular organelle (about 25–30 nm in diameter) which mediates PROTEIN SYNTHESIS (q.v. for function). Some ribosomes occur in the cytoplasm; others (see e.g. ENDOPLASMIC RETICULUM) are membrane-bound. Ribosomes are usually present in large numbers in the cell. Each ribosome consists of two subunits – one larger than the other; both subunits contain RNA and protein. Different types of ribosome are characterized by different sedimentation coefficients (S) on ultracentrifugation (see also SVEDBERG UNIT). Bacterial ribosomes have a sedimentation coefficient of ca. 70S; each consists of one 30S subunit and one 50S subunit. Ribosomes of the eukaryotic cell cytoplasm have a sedimentation coefficient of ca. 80S; each consists of one 40S subunit and one 60S subunit. Other ribosomes reported: those in mammalian mitochondria (ca. 60S), in chloroplasts of plants and algae (ca. 70S), in mitochondria of plants (ca. 78S), and those in the mitochondria of yeasts and other lower eukaryotes (ca. 73S).

NH2 N

N

N

CH2

N O H

O

P −

O

H

H

OH OH OH

O

O O

P

O

CH2

C

−

H

O

H3C

H

C

C

H

H

8

CH2

N9

N1

O

7

OH

2

OH

NH

6

H3C

N

5

10

3

4

O adenosine 5′-phosphate

riboflavin flavin mononucleotide (FMN)

flavin adenine dinucleotide (FAD)

RIBOFLAVIN and its corresponding coenzymes.

667

ribosome resulting in the formation of HAIRPINS and STEM-AND-LOOP STRUCTURES etc. [rRNA structure: ARB (1984) 53 119–162.] The integrity of a ribosome appears to involve hydrogenbonding and both ionic and hydrophobic interactions, magnesium ions generally playing an important role in maintaining the structure. The basic architecture of a ribosome has been strongly conserved during evolution, although ribosomes from e.g. bacteria, the eukaryotic cytoplasm and archaeans appear to show certain distinctive morphological features (cf. PHOTOCYTA.) [Evolving ribosome structure: ARB (1985) 54 507–530. Threedimensional model of the E. coli ribosome: Prog. Biophys. Mol. Biol. (1986) 48 67–101.] Taxonomic role of rRNA. Certain regions of rRNA have been very highly conserved during evolution, and sequence homology studies in rRNAs are widely used to indicate evolutionary relationships among organisms. [Evolutionary changes in 5S rRNA higher order structure: NAR (1987) 15 161–179.] (See also RIBOTYPING.) Biogenesis of ribosomes. Biogenesis appears to involve an assembly process in which, initially, some of the r-proteins bind to particular regions of rRNA; other r-proteins then bind cooperatively to this ‘core’ structure. [Protein–rRNA recognition and ribosome assembly: Book ref. 84, pp 331–352.] In rapidly growing cells of E. coli the number of ribosomes per cell is essentially proportional to the growth rate; this necessitates control mechanisms for co-ordinated expression of the genes encoding r-proteins and rRNAs. Genes encoding the r-proteins are grouped into a number of distinct OPERONS. For example, the str operon contains genes for (in order of transcription) S22, S7 and translation elongation factors EF-G and EF-Tu (see PROTEINS SYNTHESIS); the a operon contains genes for S13, S11, S4, RNA polymerase subunit a and L17; the b operon contains genes for L10, L7/12 and RNA polymerase subunits b and b′ . Co-ordination of the synthesis of r-proteins involves post-transcriptional AUTOGENOUS REGULATION (translational feedback regulation). One model for the control of these operons postulates that one of the r-proteins encoded by a given operon acts as a regulatory molecule (translational repressor) for that operon by binding to its own (polycistronic) mRNA and blocking translation of some or all of the encoded proteins; thus, for example, in the b operon L10 represses the translation of L10 and L7/L12, but not of the cotranscribed RNA polymerase b and b′ subunits. (See also RPO GENES.) The E. coli IF3–L35–L20 operon contains the genes infC–rpmI–rplT which encode (respectively) initiation factor IF3 (see PROTEIN SYNTHESIS) and the r-proteins L35 (sic) and L20; IF3 acts as a repressor of its own gene, and L20 apparently acts as a translational repressor (in a concentration-dependent way) by binding to a site (a translational operator ) upstream of the rpmI sequence in the mRNA, thus blocking translation of both r-proteins. The mechanism of repression by L20 is unknown, but translational control of the operon apparently involves a pseudoknot which affects the control region of rpmI [EMBO (1996) 15 4402–4413]. Some of the operon-regulatory proteins also have binding sites on either 16S or 23S rRNA. It is thought that, if the growth rate decreases, the decreased amount of 16S and 23S rRNA available in nascent ribosomes will leave these proteins free to inhibit translation of their respective transcripts. Note that, in this model, synthesis of ribosomal proteins is linked to the availability of rRNA, regulation of the rRNA genes being the key step in regulating the biogenesis of ribosomes; a ribosome

Ribosomal RNA (rRNA) comprises ca. 65% (by mass) of the bacterial ribosome, and ca. 50–60% of the eukaryotic 80S ribosome. The bacterial ribosome contains one molecule of 16S rRNA (in the 30S subunit), and one molecule each of 5S rRNA and 23S rRNA in the 50S subunit; the 16S and 23S rRNA molecules contain modified nucleotides. All three species of bacterial rRNA – together with tRNAs – are transcribed as a single molecule of RNA that is cut at specific sites; in this cutting process the ribozyme RNASE P is required for trimming the 5′ ends of tRNA molecules. Crystallographic analysis of the 30S subunit from the bacterium Thermus thermophilus has shown that (as predicted) most of the interfacial region of the subunit, i.e. that part in contact with the 50S subunit, consists of RNA [Nature (1999) 400 833–840]. (Results from the study also suggest that some of the proteins may be more directly involved in ribosomal function than has hitherto been assumed.) The eukaryotic 80S ribosome contains one molecule of 18S rRNA (in the 40S subunit), and one molecule each of 28S, 5.8S and 5S rRNA in the 60S subunit; the 28S and 18S rRNAs contain modified nucleotides (the level of modification being greater than that in bacterial 23S and 16S rRNAs). Genes which encode the 5.8S, 18S and 28S rRNAs occur in the NUCLEOLUS, the gene encoding 5S rRNA being found outside the nucleolus. (For details of rRNA synthesis see entry RRNA.) Ribosomal proteins (r-proteins). The r-proteins are closely associated with rRNA. In Escherichia coli the small (30S) ribosomal subunit contains 21 distinct r-proteins which are designated S1–S21 (‘S’ for ‘small’) – according to their electrophoretic mobilities (S1 having the highest MWt). (These proteins were also designated ES1–ES21 – ‘ES’ for ‘eubacterial small’.) Only one molecule of each type of protein is present in the subunit, and all except S1, S2 and S6 are basic proteins. (S1 is reported to be only loosely associated with the 30S subunit; there is apparently no S1 protein in the ribosomes of Bacillus spp.) The large (50S) subunit of E. coli was originally reported to contain 34 r-proteins – which were designated L1–L34 (or EL1–EL34). Subsequently, the protein initially designated ‘L8’ was found to be a complex of L7, L10 and L12; ‘L6’ was identified as S20; and L7 and L12 were found to be almost identical – differing only in that L7 is acetylated at the amino terminus. The other L proteins retained their original L numbers. All the L proteins are present in single copy except L7/L12, which is present in four copies; this is the only acidic protein in the 50S subunit. Eukaryotic 80S ribosomes are more complex; they contain >70 r-proteins. Archaeal ribosomes resemble (at least superficially) those of bacteria; for example, they contain only three types of rRNA and have a sedimentation coefficient of ca. 70S. However, those of certain archaeans (e.g. Halobacterium cutirubrum and some methanogens) contain many acidic r-proteins which show little or no homology with those of bacteria; moreover, some of the r-proteins from H. cutirubrum appear to share some homology with eukaryotic r-proteins. Furthermore, archaeal ribosomes are insensitive to certain antibiotics (e.g. CHLORAMPHENICOL) which interfere with bacterial ribosome function, while some are sensitive to the 80S (eukaryotic) ribosome inhibitor ANISOMYCIN. [Archaeal (‘archaebacterial’) ribosomes: Book ref. 157, pp 345–377.] Ribosome structure. The rRNA molecules can adopt complex secondary structures – extensive intramolecular base-pairing 668

rice ragged stunt virus (see e.g. RNASE P and self-splicing introns in SPLIT GENE). (A shortened form of the self-splicing pre-rRNA intron of Tetrahymena thermophila can, in vitro, act as an RNA polymerase and (under different conditions) as an RNase [Science (1986) 231 470–475].) The roles of ribozymes have been adapted, in the laboratory, for the cleavage or modification of specific RNA or DNA target molecules. [Characteristics and properties of ribozymes: FEMS Reviews (1999) 23 257–275.] ribulose A ketopentose (a pentulose). Phosphorylated ribulose derivatives are important intermediates in various metabolic pathways: e.g. CALVIN CYCLE, HETEROLACTIC FERMENTATION [Appendix III(b)], HEXOSE MONOPHOSPHATE PATHWAY [Appendix I(b)], PENTOSE metabolism [see e.g. Appendix III(d)], RMP PATHWAY. D-ribulose 1,5-bisphosphate carboxylase–oxygenase (RuBisCO, Rubisco, or RUBISCO; D-ribulose 1,5-bisphosphate carboxylase, RuBPCase; D-ribulose 1,5-diphosphate carboxylase; carboxydismutase) A bifunctional enzyme (EC 4.1.1.39) which catalyses the carboxylation of ribulose 1,5-bisphosphate (RuBP) in the CALVIN CYCLE and, in the presence of high levels of O2 and low levels of CO2 , the oxygenation and cleavage of RuBP to form phosphoglycolate and 3-phosphoglycerate (see PHOTORESPIRATION). RuBisCO from most sources consists of two types of subunit: ‘large’ (L) and ‘small’ (S). The L subunits appear to bear the active site; the function of the S subunits is unknown. RuBisCO containing 8 L and 8 S subunits (8L8S) has been isolated from a wide range of autotrophs, including algae, higher plants, cyanobacteria, ‘Alcaligenes eutrophus’, Paracoccus denitrificans, Pseudomonas facilis, Thiobacillus spp, etc. (In plants, the S subunits are specified by nuclear genes, the L subunits by chloroplast genes.) Rhodopseudomonas sphaeroides and R. capsulata each contain two distinct forms of RuBisCO: an 8L8S form and a 6L form (containing six L subunits only). Chlorobium thiosulfatophilum contains a 6L enzyme, Methylococcus capsulatus contains a 6L6S enzyme, while RuBisCO from Rhodospirillum rubrum contains only two L subunits. [Book ref. 115, pp. 129–173.] (See also CARBOXYSOME.) ribulose monophosphate pathway Syn. RMP PATHWAY. ribulose 5-phosphate kinase See CALVIN CYCLE. rice black-streaked dwarf virus See FIJIVIRUS. rice blast disease See BLAST DISEASE. rice diseases See CEREAL DISEASES. rice dwarf virus (RDV) A virus of the genus PHYTOREOVIRUS which infects rice (Oryza sativa) and certain other grasses. On rice, RDV causes e.g. yellowish spots or streaks on young leaves, stunting, and the formation of many small tillers which give the plant a rosette-like appearance. Vector: mainly Nephotettix cincticeps. rice gall dwarf virus (RGDV) A virus of the genus PHYTOREOVIRUS [Intervirol. (1985) 23 167–171]; RGDV is an important cause of disease in rice e.g. in Malaysia and Thailand. Infected plants are dark green, stunted, and develop small tumours on the lower surfaces of the leaves. Vector: Nephotettix spp. [RGDV structural proteins: JGV (1985) 66 811–815.] rice grassy stunt virus See RICE STRIPE VIRUS GROUP. rice hoja-blanca virus See RICE STRIPE VIRUS GROUP. rice necrosis mosaic virus See POTYVIRUSES. rice ragged stunt virus (RRSV) An unclassified virus which may have affinities with the genus FIJIVIRUS but which appears to lack an outer capsid layer; genome: 10 dsRNA segments.

feedback regulation model has been proposed in which rRNA synthesis is repressed (directly or indirectly) by the presence of ‘free’ (i.e. non-translating) ribosomes. [Review of regulation of ribosome biogenesis: Book ref. 188, pp 199–220.] Synthesis of rRNA is linked to the cell’s translational needs and is thus susceptible to up-regulation or down-regulation according to prevailing conditions. In E. coli the 16S, 23S and 5S rRNAs are co-transcribed (in that order) as a single transcript from the rrn operon; the E. coli chromosome contains seven copies of the rrn operon (designated A–E, G, H), each operon containing one copy each of the three kinds of rRNA – except the D operon, which contains two copies of the 5S gene. If (e.g. through mutation) any reduction occurs in the levels of 16S or 23S rRNA, a compensatory mechanism up-regulates the rrn operons. Interestingly, however, deletion of two or more copies of the 5S rRNA gene in E. coli brings about a sharp drop in growth rate (i.e. there is no compensatory effect) – such a reduction in growth rate being almost reversible by insertion of a plasmid-borne 5S rRNA gene [NAR (1999) 27 637–642]. ribostamycin An AMINOGLYCOSIDE ANTIBIOTIC. riboswitch In an mRNA molecule: a regulatory region consisting of an aptamer, which can bind a specific ligand, and an expression platform, which, when the ligand is bound, adopts a conformation that affects (typically inhibits) the mRNA’s function. Riboswitches occur in prokaryotes [e.g. JB (2005) 187 791–794; JB (2005) 187 8127–8136] and at least in some eukaryotes. [RibEx (for locating riboswitches): NAR (2005) 33 (Web server issue) W690–W692.] ribotype See RIBOTYPING. ribotyping A method of TYPING in which: (i) chromosomes of the test strain are fragmented by a RESTRICTION ENDONUCLEASE; (ii) the fragments are subjected to gel electrophoresis; and (iii) the gel is examined with a labelled PROBE complementary to a region in the rrn (rRNA-encoding) operon. Only those bands of fragments which bind the probe are made visible in the gel by the probe’s label (cf. DNA FINGERPRINTING). Most bacteria contain multiple copies of the rrn operon (which includes the 16S, 23S and 5S rRNA genes); moreover, the space between any two of these three genes (the intergenic spacer region) can vary in length in different copies of the operon. Consequently, hybridization of probes to fragments containing the rrn target commonly yields a fingerprint consisting of a number of bands (often 3–6). (Species which do not contain multiple copies of rrn include Mycobacterium tuberculosis and Tropheryma whipplei.) A strain defined by ribotyping is a ribotype; the ribotypes of a species reflect variation in rrn operons among strains. In Vibrio cholerae, ribotype variation may have arisen by recombination between rrn operons in the same chromosome [Microbiology (1998) 144 1213–1221]; over time, such events may be reversed, affecting long-term monitoring by ribotyping. Even so, ribotyping can be useful for monitoring under short-term or outbreak conditions – e.g. distinguishing strains of Legionella pneumophila serogroup 1(identical by routine serotyping) [FEMS Imm. (1994) 9 23–28], Vibrio parahaemolyticus [JCM (1999) 37 2473–2478] and Pseudomonas syringae [AEM (2000) 66 850–854]. (See also PCR-RIBOTYPING and RIBOPRINTER.) ribovirus A VIRUS with an RNA genome. ribozyme Any RNA molecule which can function as a catalyst (cf. ENZYME). Ribozymes occur in both eukaryotic and prokaryotic cells and e.g. in some viruses (including phages) and viroids; in nature, they are involved in processing RNA precursor molecules 669

rice-straw mushroom rickettsiae (1) Organisms of the RICKETTSIACEAE. (2) Organisms of the genus RICKETTSIA. Rickettsiales An order of Gram-negative bacteria which includes the families ANAPLAMATACEAE and RICKETTSIACEAE. rickettsialpox An acute, usually mild disease of man caused by Rickettsia akari. House mice seem to be the main reservoir of infection; the mite Allodermanyssus sanguineus transmits the pathogen to man. Incubation period: 10 days to 3 weeks. There may be a lesion at the site of the mite bite, and this is followed by sudden onset of fever with headache, chills, anorexia and photophobia; there may be a sparse maculopapular rash. The disease is usually self-limiting; no deaths have been reported. Rickettsieae A tribe of bacteria of the RICKETTSIACEAE comprising the genera COXIELLA and RICKETTSIA. The genus Rochalimaea (including R. quintana, formerly Rickettsia quintana) has been unified with the genus BARTONELLA (q.v.). Rickettsiella A genus of Gram-negative bacteria of the tribe WOLBACHIEAE; species grow intracellularly in, and are pathogenic in, arthropod hosts (including arachnids, crustaceans and insects). Growth does not occur in cell-free media. Cells: rod- or discshaped, maximum dimension typically ca. 10−4 to 10−3 M, sodium dodecyl sulphate (SDS; CH3 (CH2 )11 OSO3 Na) binds cooperatively to proteins and denatures them, forming long rod-like SDS-polypeptide complexes; virtually all proteins bind a similar amount of SDS per unit weight of protein. Each SDS molecule binds via its hydrophobic end, and the coating of SDS molecules effectively masks the charges on the polypeptide. Since the length of an SDSpolypeptide complex is roughly proportional to the molecular weight of the polypeptide, the electrophoretic mobility of such a complex will give an approximate indication of the molecular weight of the polypeptide. Thus, if the SDS complex of an unknown protein is subjected to PAGE together with the SDS complexes of reference proteins (of known molecular weights), the molecular weight of the unknown protein can be calculated by comparing the electrophoretic mobilities. Some proteins (e.g. pepsin, many viral capsid proteins) form SDS complexes only if they are heated in the presence

the appearance of a SCUTICA. Cyst formation is common. Genera include e.g. Ancistrum, Boveria, CYCLIDIUM, Loxocephalus, Parauronema, Philaster, Pleuronema, and Uronema. scutulum See FAVUS. ScV Saccharomyces cerevisiae virus (see MYCOVIRUS). scyllitol See INOSITOL. Scyphidia See PERITRICHIA. scyphus (lichenol.) See PODETIUM. scyrps See SCRNA. Scytonema A genus of filamentous CYANOBACTERIA (section IV) in which the mature trichomes are uniform in width (cf. CALOTHRIX) and are composed of disc-shaped, isodiametric or cylindrical vegetative cells; young trichomes from hormogonia each have a heterocyst at only one end. GC%: ca. 44. In nature, trichomes are heavily ensheathed and exhibit frequent FALSE BRANCHING. A distinction is often made between Tolypothrix (false branches occur singly) and Scytonema (false branches occur in pairs); however, since false branching is variable in culture, these two genera are generally considered as one, Scytonema [Book ref. 45, p. 254]. (See also STROMATOLITE.) Scytosiphon See PHAEOPHYTA. SD sequence (SD region) Shine–Dalgarno sequence: see PROTEIN SYNTHESIS. SDA Strand displacement amplification: a method for copying (‘amplifying’) a given sequence of nucleotides in DNA. Like NASBA (but unlike LCR or PCR), SDA is carried out isothermally; originally the operating temperature was ∼40° C but, owing to suboptimal specificity, it was later raised to ≥50° C (= thermophilic SDA; tSDA). SDA is considerably more complex than other nucleic-acidamplification procedures. It has two distinctive features: (i) the use of a DNA polymerase which can displace an existing strand of DNA by using the complementary strand as a template, and (ii) the use of a RESTRICTION ENDONUCLEASE for repeatedly nicking a modified cutting site in a mechanism for regenerating templates. Only certain types of DNA polymerase are able to carry out strand displacement – one of which is the exonuclease-deficient form of the KLENOW FRAGMENT. As illustrated in the figure, the strand-displacing activity of a polymerase can be manifested in two ways. In one mode, a so-called bumper primer binds upstream of the strand to be displaced; extension of the 3′ end of the bumper primer by a (strand-displacing) DNA polymerase displaces the strand downstream. (In SDA, displacement of the 5′ end of the strand begins while the 3′ end is still being synthesized.) The second mode of strand displacement occurs at a NICK site; here, the polymerase extends the 3′ end of the nick and, in so doing, displaces the downstream region of the same strand. (In effect, the 3′ end at the nick site functions as a primer.) The restriction endonuclease used in SDA is HincII; it has the (generalized) recognition site: 5′ .....GTPy/PuAC.....3′ 3′ .....CAPu/PyTG.....5′ (Py = a pyrimidine, Pu = a purine). The oblique (/) indicates the cleavage site in each strand; thus, HincII normally makes a ‘blunt-ended’ cut across both strands. The specific HincII recognition site used in SDA is: 5′ .....GTT/GAC.....3′ 3′ .....CAA/CTG.....5′ 692

B1 (a)

S1

amplicon 5′

3′

( antisense )

S1 (b)

S2

(e)

( sense )

3′

( sense )

S1

(c)

(d)

3′

B2

5′

3′

5′ 3′

3′ 5′

(f)

5′

(g)

5′

3′

3′

(h)

To amplification phase SDA (strand displacement amplification) – I: the target-generation phase (diagrammatic). The target DNA is denatured by heat to the single-stranded form prior to SDA. (a) The antisense (3′ -to-5′ ) strand of the target duplex showing the amplicon delimited by two short, vertical bars. (For clarity, and economy of space, only one strand of the amplicon is considered; corresponding events occur on the complementary strand.) A primer (S1) has bound ). A at the 3′ end of the amplicon; the 5′ end of this primer is tagged with (one strand of) the HincII recognition sequence: (5′ -GTTGAC-3′ ) ( bumper primer (B1, see entry) has bound upstream of primer S1. Extension of S1 will produce a ‘sense’ strand on the antisense template, and this strand will be displaced when B1 is extended; the displaced sense strand is shown at (b). (c) Primer S2 has bound at the 3′ end of the amplicon on the sense strand; like S1, its 5′ end is tagged with the recognition sequence of HincII. The bumper primer B2 has bound upstream of S2. Extension of S2 produces an antisense amplicon which is tagged at both ends by a HincII recognition sequence; this strand, which is displaced by the extension of B2, is shown at (d). Notice that the 3′ HincII sequence in this strand, having been synthesized with dATPaS, is modified – as indicated by ( ); this sequence is not susceptible to HincII. (d) Primer S1 (not shown) binds at the 3′ end of this strand, the HincII sequence in S1 hybridizing with the modified sequence in the strand. Extension of S1 forms the double-stranded amplicon at (e). Each end of this amplicon consists of a hemi-modified recognition site for HincII; a hemi-modified site can be nicked in the non-modified strand (arrowhead). Nicking of the upper strand at (e) is followed by extension of the 3′ end of the nick – this displacing the strand downstream of the nick site; this displaced strand is shown at (f). (g) Primer S2 binds to the displaced strand. Extension of S2 forms the product at (h). (h) This double-stranded product feeds into the amplification phase (see part II of figure).

693

PRODUCT FROM DNA SYNTHESIS ON THE TARGET ANTISENSE STRAND

(Par t I (a))

(a)

3′ 5′

(b)

3′ 5′

+

(antisense)

5′

S1 (c) 5′

AUGMENTED BY PRODUCT

(d)

FROM DNA SYNTHESIS ON TARGET SENSE STRAND

( Not shown in Part I )

(e)

+

(sense)

3′

(sense)

(f) S2 (g)

3′ 5′

SDA (strand displacement amplification) – II: the amplification phase (diagrammatic). (a) A double-stranded product from the target-generation phase; notice that this product derives from S1-primed DNA synthesis on the antisense strand of the target sequence (see part I(a)). The antisense strand in this product contains a nickable HincII restriction site (arrowhead) derived from the tag in primer S2 (see part I (g)). When this restriction site is nicked, DNA synthesis proceeds from the 3′ end at the nick site. During synthesis, the polymerase displaces the downstream section of the strand, producing an antisense copy of the target sequence which is flanked, on each side, by half a restriction site; moreover, the newly synthesized strand regenerates the original duplex – and the restriction site in this duplex is still nickable because a modified nucleotide occurs only in the 5′ -GAC-3′ sequence (see text). Both of these products (the displaced strand and the regenerated duplex) are shown at (b). Thus, the product shown at (a) can undergo repeated nicking, strand extension and regeneration in a cyclical fashion, displacing many copies of the antisense strand. (Continued on page 695.)

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secretory component of SDS – or e.g. treated with 2-mercaptoethanol (or similar reagent) to cleave intraprotein disulphide bonds. [Effect of SDS on proteins: BBA (1975) 415 29–79 (47–50).] sea ivory Ramalina siliquosa. sea lettuce Ulva lactuca: see ULVA. sea lion virus See SAN MIGUEL SEA LION VIRUS. sea sawdust See TRICHODESMIUM. seasoning (of timber) See TIMBER PRESERVATION. seaweed Any macroscopic marine alga of the CHLOROPHYTA (‘green seaweeds’), PHAEOPHYTA (‘brown seaweeds’) or RHODOPHYTA (‘red seaweeds’). seaweed diseases See ALGAL DISEASES. sec-dependent pathway See PROTEIN SECRETION. sec genes See PROTEIN SECRETION. SecA, SecB See PROTEIN SECRETION. secalonic acids Syn. ERGOCHROMES. secnidazole See NITROIMIDAZOLES. second-site reversion See SUPPRESSOR MUTATION. secondary fixation Syn. post-FIXATION. secondary fluorescence See FLUORESCENCE. secondary homothallism See HOMOTHALLISM. secondary hyphae See HYPHA. secondary metabolism Metabolism which is not essential for, and plays no part in, growth; it commonly occurs maximally under conditions of restricted growth or absence of growth (e.g. at the end of log-phase or trophophase growth in BATCH CULTURES). Secondary metabolites (‘idiolites’) include substances such as ANTIBIOTICS and MYCOTOXINS and are produced from substrates provided by PRIMARY METABOLISM – particularly shikimic acid (precursor of many aromatic compounds), amino acids (precursors of many alkaloids and antibiotics), and acetate (precursor of isoprenoids and many toxins – see also POLYKETIDE). [Review: AMP (1984) 25 1–60; secondary metabolism in fungi: Book ref. 117, pp. 336–367. Secondary metabolites: Book ref. 205.] secondary response (immunol.) See ANTIBODY FORMATION. secondary zoospore See e.g. DIPLANETISM and PLASMODIOPHOROMYCETES. secotioid fungi Fungi whose sexually-derived fruiting bodies typically resemble AGARICOID fruiting bodies but differ from them in that the margin of the pileus may not separate from

the stipe, the lamellae are characteristically convoluted, and the spores are not forcibly discharged; the secotioid fruiting body may be epigean or hypogean, the latter type closely resembling the fruiting body of a typical gasteromycete. Secotioid fungi are found in various taxa; they include e.g. certain members of the Russulales. Secotium, formerly classified in the Agaricales, is now included in the Gasteromycetes (Podaxales). [The secotioid syndrome: Mycol. (1984) 76 1–8.] Secotium See SECOTIOID FUNGI. secretin Any one type of a family of proteins which oligomerize to form pores in the OUTER MEMBRANE; in at least some cases the multimeric pores are stabilized by a specific outer membrane lipoprotein. One example of a secretin is the PilQ protein of Neisseria gonorrhoeae; this protein, which is involved in the formation of type IV FIMBRIAE, forms an outer membrane pore that is stabilized by the PilP protein. Another example is the usher protein, PapC, involved in the formation of P fimbriae (type I fimbriae); the corresponding structure is stabilized by the PapH protein. The YscC protein of the Yersinia VIRULON is a further example. secretion (of a protein) The transmembrane translocation of a protein, towards the cell’s exterior, with eventual release of the protein to the external environment. (cf. EXPORT.) secretion of proteins (by Gram-negative bacteria) See PROTEIN SECRETION. secretion sequence See ABC EXPORTER. secreton In type II PROTEIN SECRETION systems: the complex of proteins which, together, enable proteins to cross the OUTER MEMBRANE, i.e. the ‘terminal branch’ of the type II system; thus, a protein may be translocated across the cytoplasmic membrane in a sec-dependent manner and then secreted to the cell’s exterior via the secreton. The secreton is functionally analogous to the protein transport system involved in the formation of certain fimbriae [EMBO (2000) 19 2221–2228]. secretory ampulla Syn. AMPULLA sense 1 or 2. secretory component (secretory piece) A glycoprotein (MWt ca. 60000) produced (as a membrane protein) in hepatocytes and in epithelial cells of various mucosal surfaces in the body; it is a component of sIgA (see IgA). Secretory component binds to

SDA (strand displacement amplification) – II (continued) (c) Each antisense strand from (b) can bind primer S1. Extension of S1, and of the (recessed) 3′ end of the antisense strand, forms the product at (d). Extension of the 3′ end of the antisense strand has formed a modified, ) because the three terminal nucleotides in this strand (3′ -CAA-5′ ) include two modified non-nickable HincII restriction sequence ( nucleotides (dATPaS). (d) This product has a nickable restriction site (arrowhead) derived from primer S1. Like the product at (a), it can undergo a cyclical process of nicking, strand extension and regeneration, concurrently displacing copies of a single-stranded product; however, this single-stranded product is a sense strand of the target sequence. The regenerated product and sense strand are shown at (e). Recall that part I illustrates the events arising from DNA synthesis on the antisense strand of the target duplex. If events are followed on the sense strand, the resulting product is identical to that shown here at (d). (e) The single-stranded (sense) product shown here is able to bind primer S2. (f) The single-stranded product from (e) has bound primer S2. DNA synthesis (i.e. extension from S2, and also from the recessed end of the sense strand) then gives rise to the product seen at (g). (DNA synthesis at the 3′ end of the sense strand forms a non-nickable restriction site for the reason given under (c), above.) (g) This product is equivalent to the one shown at (a). Summarizing, two types of double-stranded product from the target-generation phase, derived from different strands of the target, undergo cyclical nicking, strand synthesis and regeneration, concurrently displacing numerous copies of antisense and sense strands of the target sequence. Antisense strands bind primer S1 and form the (double-stranded) product which yields sense strands; sense strands bind primer S2 and form the (double-stranded) product which yields antisense strands. Nickable HincII restriction sites are provided by the 5′ -tags on S1 and S2 primers (which are present in excess in the reaction mixture). Parts I and II reproduced from Figures 5.3 and 5.4, pages 134–137, in DNA Methods in Clinical Microbiology (ISBN 07923-6307-8), Paul Singleton (2000), with kind permission from Kluwer Academic Publishers, Dordrecht, The Netherlands.

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secretory IgA selenite broth (selenite F broth) A MEDIUM used e.g. for the ENRICHMENT of strains of Salmonella in samples of faeces; selenite inhibits many of the common enteric bacteria. The medium consists of an aqueous solution of peptone (0.5%), lactose or mannitol (0.4%), NaHSeO3 (0.4%), and either Na2 HPO4 (1.0%) or a combination of Na2 HPO4 and NaH2 PO4 to give a final pH of ca. 7.0. The medium should not be autoclaved, but may be steamed for 30 min. Incubation of the inoculated medium should not exceed ca. 12–18 hours. Selenococcidium See EIMERIORINA. Selenomonas A genus of Gram-negative bacteria (family BACTEROIDACEAE) which occur e.g. in the RUMEN and in the human gingival crevice. Cells: curved (crescent- or kidney-shaped) rods, 0.9–1.1 × 3.0–6.0 µm, with a tuft of flagella arising from the concave side of the cell. Substrates include sugars and, sometimes, amino acids and lactate; glucose fermentation yields propionic and acetic acids as major products together with e.g. CO2 and/or lactate. GC%: ca. 54–61. Type species: S. sputigena (which does not ferment cellobiose, dulcitol or salicin, and which occurs in the human mouth); other species: S. ruminantium (which ferments cellobiose, dulcitol and salicin, and which occurs in the rumen). Selenophoma A genus of fungi of the COELOMYCETES. self-cloning experiment A CLONING experiment in which the DNA to be cloned is derived from the same strain or species as that in which the recombinant DNA is to be replicated; a recombination-deficient strain may be used to prevent recombination between the cloned DNA and the organism’s genome. self fertilization (protozool.) Syn. AUTOGAMY. self purification The natural process in which organic material (faeces etc) in rivers, streams etc undergoes MINERALIZATION, and the resulting simple substances (e.g. nitrates) are made available to photosynthetic and other organisms. Self purification can occur only if the polluting load is not excessive. (See also SAPROBITY SYSTEM.) self-splicing introns See SPLIT GENE (b) and (c). self tolerance (natural immunological tolerance) Unresponsiveness of the immune system to an individual’s own (autologous) antigens. self-transmissible plasmid See CONJUGATIVE PLASMID. selfing (ciliate protozool.) Syn. CYTOGAMY. Seliberia A genus of Gram-negative, iron-accumulating, BUDDING BACTERIA which occur e.g. in soil; the organisms typically occur as radial clusters of rod-shaped cells. [Book ref. 45, pp. 516–519.] Selysina See EIMERIORINA. SEM See ELECTRON MICROSCOPY (b). semiapochromatic objective Syn. FLUORITE OBJECTIVE. semiconservative replication Replication of a double-stranded nucleic acid such that each daughter duplex contains one parental strand and one new strand. (See DNA REPLICATION.) semipermissive cells (virol.) A cell population in which only some of the cells are permissive for lytic infection by a given virus. (cf. PERMISSIVE CELLS; see also CARRIER CULTURE.) semipersistent transmission See NON-CIRCULATIVE TRANSMISSION. semi-rough mutant See SMOOTH–ROUGH VARIATION. semi-solid agar See AGAR and MEDIUM. Semliki Forest virus (SFV) An ALPHAVIRUS which was first isolated from mosquitoes in Uganda. Its natural hosts and vectors are unknown, but antibodies to the virus have been detected in humans and wild primates in various parts of Africa, Malaya and North Borneo. The virus is apparently non-pathogenic in

the dimeric IgA–J chain complex at the basal surface of (e.g.) a mucosal epithelial cell; the (IgA)2 –J chain–secretory component complex is then taken into the cell by endocytosis and passes through the cell cytoplasm (in an endocytotic vacuole), sIgA being released at the mucosal surface by proteolytic cleavage of the (transmembrane) secretory component. secretory IgA See entry IgA. section (histol.) See MICROTOME. sectoring (in a colony) The development of a sector or wedgeshaped region of growth which differs, in e.g. appearance, from the rest of the colony. SecYEG See PROTEIN SECRETION. sedentary Syn. SESSILE (sense 1). sedimentation basin See WATER SUPPLIES. sedimentation coefficient See SVEDBERG UNIT. sedoheptulose A 7-carbon ketosugar originally isolated from Sedum sp (stonecrop: Crassulaceae) in which it occurs as the free monosaccharide. Phosphorylated derivatives of sedoheptulose are intermediates in the CALVIN CYCLE, the HEXOSE MONOPHOSPHATE PATHWAY [Appendix I(b)], and the RMP PATHWAY. seed (verb) To inoculate. seeligerolysin See THIOL-ACTIVATED CYTOLYSINS. segmented genome In a virus: a genome which occurs as two or more pieces of nucleic acid. (See e.g. ARENAVIRIDAE, BACTERIOPHAGE f6, BUNYAVIRIDAE, ORTHOMYXOVIRIDAE, REOVIRIDAE.) segregation (genetics) The separation of homologous chromosomes or chromatids, or homologous or non-homologous (incompatible) plasmids, or of particular named genes or alleles, etc, into different daughter cells during cell division. segregation lag A delay in the phenotypic expression of a newly acquired genotype owing to the time required for the segregation of the new allele(s) to a cell which has no corresponding wildtype allele(s). Thus, e.g., if a mutation occurs in one chromosome in a bacterial cell which contains two or more chromosomes, the mutant phenotype will be expressed only when the mutant chromosome is segregated (by cell division) into a cell which lacks a wild-type chromosome. segregational petite See PETITE MUTANT. Seitz filter See FILTRATION. selC gene See PATHOGENICITY ISLAND. selectins A family of calcium-dependent CELL ADHESION MOLECULES with the properties of LECTINS. E-selectin (see CD62E) is expressed on endothelial cells during INFLAMMATION. Lselectin (LECAM-1; = CD62L) occurs on leukocytes, and is involved in lymphocyte homing and in the interaction between leukocytes and endothelium during inflammation. Pselectin (PADGEM; = CD62P) is found e.g. on (activated) platelets and endothelial cells during inflammation; in the unstimulated state, P-selectin occurs in a granules in platelets and within endothelial cells. P-selectin is the largest of the selectin molecules (140 kDa); the lymphocyte-associated form of L-selectin is the smallest (∼75 kDa). selection synchrony See SYNCHRONOUS CULTURE. selective medium See MEDIUM. selenate respiration ANAEROBIC RESPIRATION, found in certain (Gram-positive and Gram-negative) bacteria (e.g. Thauera selenatis [IJSB (1993) 43 135–142]), in which the terminal electron acceptor is selenate. Some species of bacteria can use arsenate as terminal electron acceptor. [Arsenic- and selenium-respiring bacteria: FEMS Reviews (1999) 23 615–627.] selenazofurin See RIBAVIRIN. selenazole See RIBAVIRIN. Selenidium A genus of the GREGARINASINA. 696

septum man. When injected into mice, SFV can cause an acute, lethal encephalitis; virulent strains appear to damage neurones (or particular neurone subsets) directly, while other strains infect oligodendrocytes and cause demyelination – apparently by triggering an autoimmune response [JGV (1985) 66 2365–2373; review: JGV (1985) 66 395–408]. SFV can be transmitted transplacentally in mice, causing e.g. abortion or malformation of infected fetuses. (See TOGAVIRIDAE for replication cycle etc.) Semple vaccine An anti-RABIES vaccine consisting of a phenolinactivated preparation of rabbit-fixed rabies virus (i.e. rabies virus passaged in rabbit brain). sen gene See EIEC. Sendai virus See PARAMYXOVIRUS. senior synonym See SYNONYM. sennetsu rickettsiosis See EHRLICHIA. sens. lat. SENSU LATO (q.v.). sense codon A codon which specifies an amino acid: see GENETIC CODE. sense strand (of DNA) See CODING STRAND. sensitin Any preparation (e.g. an extract of a given microorganism, as in brucellin, coccidioidin etc) which can act as an ALLERGEN; sensitins are used in SKIN TESTS. sensitivity agar Any of various standardized, solid, agar-based media used for carrying out ANTIBIOTIC-sensitivity tests. sensitization (immunol.) (1) (of a person or animal) The initial exposure of an individual to an allergen such that a manifestation of HYPERSENSITIVITY occurs on subsequent exposure(s) of the individual to that allergen. (2) (of persons, animals or cells) The process of priming (see PRIMED). (3) The combination of cell-surface antigens with their homologous antibodies (see e.g. HAEMOLYTIC SYSTEM). (4) The coating of erythrocytes with soluble antigens (see BOYDEN PROCEDURE). (5) Any procedure of the type in which certain strains of staphylococci are coated (‘sensitized’) with unrelated antibodies (see PROTEIN A) for use in a PASSIVE AGGLUTINATION TEST for the homologous antigen. (6) The combination of cells with cytophilic antibodies (see e.g. REAGINIC ANTIBODIES). sensu lato (s.l.; sens. lat.) Of a term or name: (1) used in a broad or more inclusive sense, or (2) used with a meaning other than the original meaning. sensu stricto (s.s.; s. str.) Of a term or name: (1) used with a precise or narrow meaning, or (2) used with the original meaning. Seoul virus See HANTAVIRUS. sepB gene See PATHOGENICITY ISLAND. Sephadex See DEXTRANS and GEL FILTRATION. Sepik virus See FLAVIVIRIDAE. sepsis (med., vet.) (1) The state in which pathogen(s) are present in particular tissue(s). (cf. ASEPSIS; SEPTICAEMIA.) (2) The symptoms associated with microbial infection of tissues. (See also SIRS.) septa Plural of SEPTUM. septal pore cap See DOLIPORE SEPTUM. septate Having one or more septa. septic (1) (med., vet.) Refers to SEPSIS (generally sense 2). (2) Refers to the presence or activities of microorganisms involved in putrefaction or decay (see e.g. SEPTIC TANK). septic diphtheria See DIPHTHERIA. septic shock Syn. ENDOTOXIC SHOCK. septic tank A ventilated tank into which domestic sewage flows and within which the sewage undergoes primary purification (settlement of suspended solids) and some degree of ANAEROBIC DIGESTION; solids (sludge and scum) are periodically removed for disposal. The highly polluting supernatant overflows and

must be treated, e.g. by aerobic biological oxidation or (when permissible, and when underground water supplies would not be contaminated) allowed to disperse in the soil below the surface (‘subsurface irrigation’). A septic tank can serve e.g. 1–50 houses. (cf. CESSPOOL; see also SEWAGE TREATMENT.) septicaemia (septicemia; blood poisoning) A particular form of BACTERAEMIA in which there are clinical symptoms (e.g. fever). The term may also refer to the presence of Candida albicans or other fungi in the bloodstream. (cf. VIRAEMIA.) (See also SEPSIS and SIRS.) septicemia Syn. SEPTICAEMIA. septicolysin See THIOL-ACTIVATED CYTOLYSINS. Septobasidiales An order of fungi (subclass PHRAGMOBASIDIOMYCETIDAE) which form non-gelatinous fruiting bodies; they include parasites of scale insects (insects of the superfamily Coccoidea). Genera: Septobasidium and Uredinella. Septobasidium See SEPTOBASIDIALES. septoria A plant disease caused by a species of Septoria: see e.g. GLUME BLOTCH and HALO SPOT. Septoria A genus of fungi (order SPHAEROPSIDALES) which include many plant pathogens – e.g. S. apiicola, the causal agent of late blight (leaf spot) of celery. (See also e.g. GLUME BLOTCH and HALO SPOT.) Conidia are filiform and typically multiseptate and colourless; they are formed in dark, ostiolate pycnidia immersed in the substratum. septum (cross-wall) (a) (bacteriol.) A partition which (i) divides a parent cell into daughter cells during BINARY FISSION, (ii) occurs between adjacent cells in a filament (see e.g. ACTINOMYCETALES), and (iii) separates a developing ENDOSPORE from the rest of the mother cell. Septum formation is an essential phase in the CELL CYCLE (q.v. for details of septum formation in bacteria). During sporulation in Bacillus subtilis, one of the early stages is the formation of an asymmetric septum, i.e. one which (unlike that formed during cell division) develops near one pole of the cell. Initially, an FtsZ ring (see CELL CYCLE) forms at the midcell position but then become helical and finally forms an FtsZ ring at both polar sites; septation occurs at only one site [Science (2002) 298 1942–1946]. (b) (mycol.) A partition, one or more of which divides certain fungal structures (hyphae, spores etc.) into cells; septa are also formed in fission yeasts (e.g. Schizosaccharomyces) during cell division. A primary septum is one formed in association with nuclear division, i.e. one serving to separate daughter cells. An adventitious septum develops independently of nuclear division. Septate hyphae are characteristic of the higher fungi, but septa are also formed in certain lower fungi – although often only in ageing hyphae and/or in order to delimit reproductive structures (such as sporangia). Septate (multicellular) spores are formed by various fungi (e.g. macroconidia in Fusarium). In general, ‘true’ septa (eusepta) have essentially the same composition as the hyphal CELL WALL, but certain fungal structures (e.g. the mycelium of some of the more complex chytridiomycetes, and the conidia in certain hyphomycetes) have septum-like pseudosepta (= distosepta) whose composition is distinct from that of the cell wall. Hyphal septa appear always to be formed by centripetal growth from annular rims which develop on the inner surface of the hyphal wall. In some cases growth of the septum continues inwards until a complete plate is formed. In other cases, growth stops before the septum is complete, so that a small pore (ca. 697

sequence capture PCR being linked to the conversion of glyoxylate to glycine. The reaction sequence continues thus: hydroxypyruvate → glycerate → 2-phosphoglycerate, the latter either being converted to 3phosphoglycerate (phosphoglycerate mutase, EC 2.7.5.3) and assimilated into biomass, or converted to phosphoenolpyruvate (PEP). CO2 enters the cycle at this point: with PEP (PEP carboxylase, EC 4.1.1.31) it forms oxaloacetate. The cycle continues oxaloacetate → malate → malyl-CoA, the latter being split (by a lyase, EC 4.1.3.24) to glyoxylate (used to regenerate glycine – see above) and acetyl-CoA. Acetyl-CoA with oxaloacetate (citrate synthase) initiates a subsidiary cycle, first forming citrate and then isocitrate – which is split (isocitrate lyase, EC 4.1.3.1) to glyoxylate and succinate, the latter being converted, in several steps, to oxaloacetate which re-enters the subsidiary cycle [see Appendix II(b)]; as before, glyoxylate is used to regenerate glycine. The pathway described above is referred to as the icl or icl+ (isocitrate lyase) serine pathway. Some organisms which use the serine pathway (e.g. ‘Pseudomonas AM1’) contain neither malate thiokinase (and hence cannot form malyl-CoA) nor isocitrate lyase (and hence cannot regenerate glyoxylate in the subsidiary cycle); the pathway in these organisms is called the icl− serine pathway. The way in which acetyl-CoA is used to regenerate glyoxylate (and glycine) in the icl− serine pathway is not yet understood; in the proposed ‘homo-isocitrate pathway’ acetyl-CoA condenses with 2-oxoglutarate to form homocitrate and then homoisocitrate which is cleaved to glyoxylate and glutarate – the latter being used to regenerate 2-oxoglutarate. serine proteases See PROTEASES and type II systems in PROTEIN SECRETION. seroconversion The development of antibodies in response to exposure to antigen. seroconversion illness See AIDS. serodiagnosis Diagnosis based on serological tests. serofactor 1 See YERSINIA (Y. pestis). serofast Refers to a patient whose serum (sampled at intervals of time) consistently gives positive results in a given serological test. serological tests for syphilis Syn. STANDARD TESTS FOR SYPHILIS. serological typing See TYPING. serology The study of in vitro reactions involving one or more of the constituents of SERUM (e.g. a particular type of ANTIBODY, or a component of COMPLEMENT) or of PLASMA (see e.g. clumping factor in COAGULASE); serology is used e.g. in medical diagnostic procedures to detect and/or quantify particular antigens or antibodies. See e.g. HAEMAGGLUTINATION-INHIBITION TEST, IMMUNOASSAY, WIDAL TEST. serotonin 5-Hydroxytryptamine: a base (derived from tryptophan) with physiological activity similar to that of HISTAMINE; it occurs e.g. in the platelets of many species, and is also found e.g. in the MAST CELLS and basophils of some species. (See also ENTEROCHROMAFFIN CELLS.) serotype (serological type; serovar) A serologically (antigenically) distinct VARIETY (usually) within a bacterial species. serotyping A method of TYPING in which strains are distinguished on the basis of differences in their surface ANTIGENS (e.g. cell wall, flagellar and/or capsular antigens). Essentially, each strain to be typed is tested with a variety of antibodies (different antibodies being specific for antigens on different strains of the organism). If the cells of an unknown (i.e. untyped) strain bind a particular antibody (indicated in vitro by agglutination or precipitation of the cells), the unknown strain is placed in the same category (type) as the strain homologous to that antibody.

0.4–1.0 µm diam.) remains in the centre of the septum; such pores (characteristic of ascomycetes) may permit passage of cytoplasm and nuclei from one hyphal cell to the next, but in many fungi the pores may be plugged or occluded (see e.g. WORONIN BODIES). Plasmodesmata (fine, cytoplasm-filled channels) occur in the septa of certain fungi. (See also DOLIPORE SEPTUM.) sequence capture PCR See PCR and DYNABEADS. sequencing (of DNA and RNA) See DNA SEQUENCING. Sequestrene Syn. VERSENE. SER Smooth ENDOPLASMIC RETICULUM. sera Plural of SERUM. SERE Salmonella enteritidis repetitive element: a widely dispersed bacterial repetitive DNA element [JMM (1998) 47 489–497]. (See also REP-PCR.) SERE-PCR See REP-PCR. Ser´eny test A test used with the intention of determining the invasiveness of a bacterial pathogen. The conjunctival sac of a guinea pig is inoculated with the pathogen; invasiveness is indicated by ulceration of the cornea. An HEp-2 tissue culture test may be used as a more humane alternative [JCM (1981) 13 596–597.] serial dilutions A set of dilutions (of a given sample) prepared by initially diluting an aliquot of the sample, then diluting an aliquot of this dilution, and so on. In doubling dilutions the dilution factor progressively doubles: 1/2, 1/4, 1/8 etc. In log dilutions the dilution factors are related thus: 1/10, 1/100, 1/1000 etc. serial passage (1) (syn. passage) Any procedure in which a pathogen (usually a virus) is transferred from one to another of a succession of animals, eggs or tissue cultures etc – growth (or replication) of the pathogen taking place before each transfer. Serial passage is sometimes used e.g. for the ATTENUATION (sense 1) of a pathogen. For example, the rabies virus may be attenuated by adapting it to chick embryo tissues – the virus being serially passaged through a series of hens’ eggs. (See also AVIANIZED VACCINE and FLURY VIRUS.) For use in a vaccine, a successfully passaged pathogen should (a) be non-pathogenic for particular host(s), and (b) retain its specific immunogenicity in order to stimulate the formation of protective antibodies. (2) In TISSUE CULTURE, ‘passage’ refers to the transfer of an inoculum of cells from an existing cell culture to fresh growth medium in another vessel (i.e. subculture); ‘serial passage’ refers to repeated subculture. (This contrasts with the serial passage of a virus in tissue cultures: when a virus is passaged the supernatant is transferred.) series A taxonomic rank (sometimes used in mycology) between subclass and order. L-serine biosynthesis See Appendix IV(c). serine pathway A cyclic metabolic pathway used by some types of methylotrophic bacteria for the assimilation of 1-C substrates (see METHYLOTROPHY). (A strain of Streptomyces has been reported to use both the serine pathway and the RMP PATHWAY, while at least some moulds (as opposed to yeasts) apparently use the serine pathway [Book ref. 3, p. 180].) In those methylotrophic bacteria which use the serine pathway, 1-C substrates are assimilated partly as formaldehyde (HCHO) and partly as CO2 . HCHO condenses with tetrahydrofolate (THF), thus forming 5,10-methylene-THF (MTHF); MTHF with glycine (enzyme: serine hydroxymethyltransferase, EC 2.1.2.1) yields serine and regenerates THF. Serine is deaminated (serine glyoxylate aminotransferase, EC 2.6.1.45) to hydroxypyruvate – this reaction 698

severe combined immunodeficiency Serotyping may be carried out in small test tubes (see also or on slides (see SLIDE AGGLUTINATION TEST). (See also LATEX PARTICLE TEST.) Strains distinguished mainly on the basis of their antigens are called serotypes. serovar Syn. SEROTYPE. Serpens A genus (incertae sedis) of catalase-positive, oxidasepositive, microaerophilic, chemoorganotrophic, Gram-negative bacteria which occur e.g. in sediments in freshwater ponds. Cells: flexible rods or filaments, 0.3–0.4 × 8.0–12.0 µm, which have bipolar tufts of flagella (4–10 flagella in each tuft) and some lateral flagella; the cells can exhibit motility in liquids of low and high viscosity, and a ‘serpentine-like’ motility within agar gels. Metabolism is respiratory (oxidative), with oxygen as terminal electron acceptor. The principal source of carbon and energy is lactate; carbohydrates are not used. NH4 Cl or e.g. peptone (but not nitrite or nitrate) can serve as a source of nitrogen. Optimum temperature: 28–30° C. GC%: ca. 66. Type species: S. flexibilis. [Book ref. 22, pp. 373–375.] Serpula A genus of fungi of the APHYLLOPHORALES (family Coniophoraceae). S. lacrymans (formerly Merulius lacrymans) causes DRY ROT; it typically forms a thick, resupinate, leathery, initially pale grey fruiting body which, when the basidiospores develop, becomes rusty red with a pale mycelial margin. The hymenium may be wrinkled or shallowly pitted, or it may occur on a layer of irregularly shaped, pendulous, tooth-like processes (the so-called ‘stalactite’ fruiting body); basidiospores: ellipsoidal, ca. 5 × 10 µm. serrated wrack Fucus serratus. Serratia A genus of Gram-negative bacteria of the ENTEROBACTERIACEAE (q.v.). Cells: 0.5–0.8 × 0.9–2.0 µm, usually motile. Some species and strains produce the non-diffusible pigment PRODIGIOSIN, forming colonies that are red or have red centres, margins or sectors; prodigiosin production is optimum on peptone–glycerol agar at 20–35° C, and occurs only under aerobic conditions. In the presence of Fe2+ , some strains of S. marcescens produce a water-soluble pink pigment pyrimine, L-2-(2-pyridyl-1′ -pyrroline-5-carboxylic acid), which diffuses into the agar surrounding the colonies. Typical reactions: citrate +ve; MR −ve; VP +ve at 30° C, but may be −ve at 37° C (O’Meara’s method may be −ve); extracellular enzymes include gelatinase, lipase and DNase. Glucose is fermented by the ENTNER–DOUDOROFF PATHWAY. Lactose +ve or −ve, according to species. GC%: 52–60. Type species: S. marcescens. S. ficaria. Prodigiosin −ve. Cultures have a musty, potatolike odour. Occurs mainly in association with figs and fig-wasps [Curr. Micro. (1979) 2 277–282]. S. fonticola. Atypical (species incertae sedis). S. liquefaciens (formerly Enterobacter liquefaciens). Prodigiosin −ve. A heterogeneous species which may be split into three: S. liquefaciens sensu stricto, S. proteamaculans and S. grimesii. S. marcescens. Biogroups A1 and A2 produce prodigiosin. Some strains produce pyrimine. S. marcescens is reported to exhibit a flagellum-independent spreading motility in which surface tension may be involved [JB (1995) 177 987–991]. S. odorifera. Prodigiosin −ve. Cultures have a musty, potatolike odour. S. plymuthica. Most strains produce prodigiosin. S. rubidaea (= S. marinorubra). Most strains produce prodigiosin. Serratia spp occur in water and soil, on plants, in insects, and in man and animals (see also DFD MEAT). S. marcescens

and S. liquefaciens may cause lethal septicaemia in insects [JGM (1983) 129 453–464]. Species have also been associated with disease in reptiles, spoilage of hens’ eggs, bovine mastitis etc. In man, S. marcescens (especially non-pigmented strains) are increasingly frequent causes of nosocomial infections (e.g. pneumonia, UTI). (See also PSEUDOHAEMOPTYSIS; RED DIAPER SYNDROME.) [Book refs. 22, pp. 477–484, and 46, pp. 1187–1203.] serum The fluid fraction of coagulated (clotted) blood; it differs from PLASMA e.g. in that it does not contain FIBRINOGEN (a factor in the clotting mechanism). Normal serum contains e.g. various nutrients, electrolytes, albumins, immunoglobulins, waste products. serum amyloid A See ACUTE-PHASE PROTEINS. serum hepatitis Syn. HEPATITIS B. serum killing The killing of some strains of Gram-negative bacteria, by either immune or non-immune serum, due mainly or solely to activation of the alternative pathway of COMPLEMENT FIXATION; such serum sensitivity may be greater in rough mutants and less or non-existent in capsulated strains [JGM (1983) 129 2181–2191]. (See also SURFACE EXCLUSION.) serum sensitivity See SERUM KILLING. serum sickness A systemic condition, involving a TYPE III REACTION, which may occur ca. 8 days after the initial administration of a large amount of antigen (given e.g. during passive immunization); in such cases antigen is still circulating when antibody first appears in the plasma, and soluble antigen–antibody complexes are formed due to ANTIGEN EXCESS. A generalized inflammatory reaction occurs, with fever, enlargement of lymph nodes, swelling of joints, a generalized urticarial rash, and sometimes renal dysfunction. (cf. GLOMERULONEPHRITIS.) serum sugars See PEPTONE-WATER SUGARS. serum water sugars See under PEPTONE-WATER SUGARS. sessile (1) Of an organism (e.g. a protozoon): attached to the substratum (with or without a stalk), i.e., not free-swimming. (2) Of a fruiting body, spore etc: attached directly, i.e., without a stalk, to the substratum, sporophore etc; e.g., the sessile basidiospores of the smut fungi lack sterigmata, arising directly from the basidia. Sessilina See PERITRICHIA. sessilinid A member of the Sessilina. seston All the fine particulate matter which drifts passively in lakes, seas and other bodies of water; it includes PLANKTON and TRIPTON. set2 gene See EIEC. seta (pl. setae) A bristle-like structure. Setae occur e.g. in some types of fungal fruiting body; in some species of Colletotrichum, some of the setae which occur in acervuli have truncated, nearcolourless apices which give rise to conidia, while the darker, usually pointed setae are sterile [Mycol. (1984) 76 359–362]. setose Bearing setae – see SETA. severe combined immunodeficiency (SCID) A heterogeneous group of immune deficiency diseases in which the common feature is a block in the development of T lymphocytes; in some of these diseases there is also a deficiency in B lymphocytes and/or NK cells. A consequence of such immunodeficiency is a marked susceptibility to opportunist pathogens coupled with a poor prognosis. (cf. DIGEORGE SYNDROME.) One of the SCID diseases is ADENOSINE DEAMINASE DEFICIENCY (q.v.), resulting from mutation in the ADA gene. Another of these diseases is caused by mutation in the gene encoding the gc subunit that is common to the cell-surface receptors of various CYTOKINES – including the interleukins IL2, IL-4, IL-7, IL-9 and IL-15 [see e.g. Cell (1993) 73 147–157];

DREYER’S TUBE)

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severin deficiency in the receptor for IL-7 inhibits development of T cells, while deficiency in the receptor for IL-15 inhibits development of NK cells. The gene encoding the gc subunit occurs on the X chromosome, and this (X-linked) disease is designated XSCID of SCIDX1. SCIDX1 can be treated successfully by GENE THERAPY: CD34+ cells were infected, ex vivo, with a retrovirus-derived vector carrying the gene for gc [Science (2000) 288 669–672]. In one patient, however, this therapy apparently caused a leukaemia-like illness [Nature (2002) 420 116–118]. During normal stimulation of cell-surface receptors containing the (wild-type) gc subunit, a kinase, designated JAK-3, binds to the intracellular domain of gc as part of the intracellular signalling process. A phenotype similar to that of SCIDX1 can therefore be caused by mutation in the JAK-3 gene which inactivates the kinase; unlike the gene encoding gc, JAK-3 is an autosomal gene, and mutations in JAK-3 give rise to an autosomal recessive form of the disease in which (like the Xlinked form) both T cells and NK cells are affected. [Primary immunodeficiency diseases (an experimental model for molecular medicine): Lancet (2001) 357 1863–1869 (SCID: 1864–1865).] severin See ACTIN. sewage fungus Slimy, macroscopic masses of mixed microbial growth which develop on rocks etc in many organically polluted (e.g. sewage-polluted) freshwater habitats. The organisms which contribute to sewage fungus are typically those which occur as part of the normal microflora of the habitat; they include bacteria (e.g. Sphaerotilus natans, Zoogloea spp), fungi (e.g. Fusarium spp, Geotrichum candidum), protozoa (e.g. Carchesium polypinum), and algae (e.g. Stigeoclonium spp). Usually, a particular sample of sewage fungus contains one, or a few, dominant species; the dominance of a given species may correlate e.g. with the availability of a particular carbon source. sewage treatment Sewage includes domestic wastes (from drains, water closets etc.) – sometimes with varying amounts of agricultural and/or industrial effluent – and (often) the contents of rain-water drains; it contains substances in suspension, in solution and in colloidal form. If discharged to environmental waters, sewage can be harmful in several ways. For example, it can act as a source of infection – encouraging the spread of water-borne diseases such as CHOLERA and TYPHOID FEVER. (See also SHELLFISH POISONING.) Another problem is its content of biodegradable organic matter. In metabolizing these nutrients, the large numbers of sewage organisms can rapidly deplete the oxygen at a locally polluted site, especially in slow-moving or static waters; the consequent development of a microaerobic or anaerobic environment means a loss of habitat for all oxygen-dependent organisms (e.g. fish) in the vicinity. Moreover, anaerobic conditions allow the growth of SULPHATE-REDUCING BACTERIA and other microorganisms whose metabolic products include sulphide and other malodorous substances. Sewage treatment has two main objectives: (i) to eliminate (or reduce the numbers of) pathogens which cause water-borne diseases, and (ii) to diminish the oxygen-depleting capacity of sewage, i.e. to reduce its BOD. Small quantities of sewage (e.g. from one or several houses in isolated rural areas) may be treated in a SEPTIC TANK. Large-volume sewage (from urban areas) is treated by a twostage process, described below. Primary treatment may involve simply passing the raw (i.e. untreated) sewage through a screen of metal bars to separate, and

dispose of, the grosser debris; the screened sewage may then be passed through a comminutor (a rotary shredding device which breaks up the smaller solids). The screened, comminuted sewage effluent then passes slowly through a sedimentation (settlement) tank in which some particulate matter settles out (and is removed as sludge). Sedimentation is sometimes assisted by the addition of alum as the effluent enters the sedimentation tank. Secondary treatment is designed to reduce the BOD of the primary effluent to acceptable levels by microbial oxidation of the dissolved organic content. This is usually achieved by one of three types of (aerobic) process: the trickle filter, the activated sludge process and the (more recent) biological aerated filter (BAF); these processes are considered below. The trickle filter (biological filter, percolating filter ) consists of a bed of crushed rock, ca. 2 m deep, over which the primary sewage effluent is sprayed. The bed of rock may be enclosed within a circular wall, the sewage being sprayed through holes in the arms of a rotary sprinkler; with a rectangular bed of rock, sewage is sprayed from a distributor arm moving backwards and forwards. The rock surface bears a film of microorganisms – for example, the bacterium Zoogloea ramigera and species of ciliate protozoa (e.g. Carchesium, Chilodonella, Opercularia and Vorticella). (Also commonly present are e.g. rotifers, crustaceans, insects and arachnids.) Percolating slowly through the crushed rock, the sewage makes close contact with surfaces that bear the biofilm. The sprayed sewage carries with it dissolved oxygen, so that some of the dissolved organic matter can be oxidized by organisms in the sewage and by those in the biofilm; moreover, some dissolved organic carbon is assimilated, as biomass, by these organisms. The system is not intended to act as a mechanical sieve – but rather to permit close contact between the biofilm and sewage under aerobic conditions; this reduces the level of dissolved organic matter. Moreover, large numbers of sewage bacteria are ingested by protozoans in the biofilm. Effluent leaving the bed usually contains small particles of biofilm washed from the rock; these particles may be allowed to settle in a humus tank before the supernatant is discharged as the final effluent. The final effluent has a much lower BOD – so that, if discharged to a river etc., it will take less oxygen from the water. The activated sludge process is another form of aerobic secondary treatment. Effluent from the primary treatment stage enters a vessel containing activated sludge – a mass of organisms consisting mainly of bacteria (e.g. species of Acinetobacter and Alcaligenes, Sphaerotilus natans and Zoogloea ramigera) and protozoa; the latter include ciliates (e.g. Aspidisca, Carchesium, Opercularia, Trachelophyllum, Vorticella), flagellates, and the testate amoebae Cochliopodium and Euglypha – amoebae often being found in large numbers and sometimes forming the major component of the biomass. Other organisms present include fungi, rotifers and nematodes. Effluent and sludge are vigorously agitated and aerated for e.g. 6–12 hours so that much of the soluble organic matter in the effluent is oxidized, or assimilated, by the biomass; the BOD is thus greatly reduced, and large numbers of sewage bacteria are ingested by protozoa. The treated effluent is then left in a sludge-settling tank. Good-quality final effluent depends on efficient flocculation (= aggregation) of the organisms, this facilitating clarification of the effluent by sedimentation. Flocculation is encouraged by cell-surface hydrophobicity which promotes (i) adherence of cells to flocs, and (ii) penetration of the flocs by cells via channels/pores within the 700

shaded matrix flocs [see Microbiology (1998) 144 519–528]. [Microbial communities in sewage treatment plants: FEMS Ecol. (1998) 25 205–215.] In this process, the sludge increases in mass due to microbial growth; following sedimentation, most is removed for disposal, some being retained for treating the next batch of sewage. The biological aerated filter (BAF) is a more efficient approach to aerobic secondary treatment. It consists of a submerged bed of fine granular material coated with biofilm; the sewage passes downwards through the bed while air is pumped in at the base of the bed. Because the granules are small, the system can function as a mechanical filter (for fine particulate matter) as well as allowing mineralization of dissolved organic matter. The biofilm in a BAF contains up to five times more biomass than that in a trickle filter of equivalent size – so that, for a given treatment capacity, a BAF can be much smaller. Appropriate flow conditions in the BAF allow adequate aeration and the establishment of nitrifying bacteria in the biofilm. The importance of this is that NITRIFICATION facilitates the elimination of nitrogen from sewage; thus, if nitrification can be achieved it can be followed by DENITRIFICATION. To encourage denitrification the BAF can be operated anaerobically; much of the nitrogen in sewage can therefore be eliminated by operating aerobic and anaerobic BAF reactors in series. [Combined nitrification–denitrification: FEMS Reviews (1994) 15 109–117.] Anaerobic treatment is useful for sewage containing a high proportion of solids (e.g. farm waste, sludge from the activated sludge process). In this process (ANAEROBIC DIGESTION), the stirred sludge is digested in a tank maintained at ca. 35° C. This reduces the bulk of sludge, giving a less offensive material which can be de-watered in sludge-drying beds; much of the carbon is eliminated as methane (which can supply most or all of the energy needs of the plant). (See also IMHOFF TANK.) Anaerobic treatment can also be used e.g. for wastewater containing terephthalic acid (1,4-benzenedicarboxylic acid) and its isomers – compounds used in the manufacture of polyester products and plastic bottles; in one study, organisms associated with the anaerobic granular sludge system included a high proportion of unidentified bacteria of the d-Proteobacteria and a number of archaeans related to Methanosaeta and Methanospirillum [Microbiology (2001) 147 373–382]. Tertiary treatment is sometimes used to reduce still further the BOD of the effluent; this may be needed e.g. if discharge of final effluent to a river is associated with a low dilution factor. To reduce the amount of fine particulate matter, the effluent can be passed through a microstrainer : a hollow cylinder of finemesh stainless steel fabric, closed at one end, which rotates on a horizontal axis; effluent is pumped into the cylinder, and strained effluent passes out through the mesh – material retained on the inner surface of the cylinder being constantly removed by jets of water. The Immedium filter is a sand filter in which the grain size increases progressively from top to bottom; effluent flows upwards through the filter. Other forms of filter, and grassland irrigation, are also used for tertiary treatment. The main purpose of tertiary treatment is often regarded as the reduction of BOD by elimination of carbon from the effluent. However, removal of nitrogen (present mainly as ammonia and nitrate) and phosphorus is also desirable in order to discourage the development of algal BLOOMS in the receiving waters. (See also EUTROPHICATION.) The elimination of nitrogen was considered earlier (see BAF). Phosphorus has been removed

by using a cycle of alternating anaerobic and aerobic treatments. Anaerobically, some organisms increase in biomass but release phosphorus; aerobically, the (increased) biomass assimilates phosphorus – and is subsequently separated and disposed of. The bacterium Acinetobacter calcoaceticus is reported to accumulate phosphate (up to ∼10% dry weight), >50% as POLYPHOSPHATE. [Biological phosphorus removal: MS (1984) 1 149–152. Identification of polyphosphate-accumulating bacteria for biological phosphorus removal in activated sludge plants: AEM (2000) 66 1175–1182.] Disinfection of final effluent has been carried out with e.g. CHLORINE or OZONE. In at least one plant in the USA, dewatered sludge (50% solids) has been disinfected with IONIZING RADIATION (dose: 1 Mrad from a 137 caesium gamma source). [Bacterial activities in sewage treatment plants: AvL (1984) 50 665–682. Environmental health engineering in the tropics: Book ref. 216. Low-cost sewerage for developing countries: Book ref. 217.] sewer gas See ANAEROBIC DIGESTION. sewer swab Syn. MOORE SWAB. sex factor (1) A general term for a CONJUGATIVE PLASMID (sense 1). (2) Collectively, those genes in a conjugative plasmid which specify conjugation (see e.g. RTF). (3) Syn. F PLASMID. sex pheromone See PHEROMONE. sex pili See PILI. sex-ratio organism See SRO. sexduction The transfer, by CONJUGATION (sense 1b), of chromosomal genes from one bacterium to another. Sexduction may involve an HFR DONOR or a donor strain carrying a PRIME PLASMID; if the chromosome of the Hfr donor is mobilized by the F PLASMID, or if conjugal transfer is promoted by an F′ plasmid, the process is called F-duction. sexually transmitted disease (STD) Any disease which can be transmitted by intimate contact with e.g. genitals, mouth or rectum. In addition to the ‘classical’ VENEREAL DISEASES, STDs include e.g. AIDS, HEPATITIS B, HERPES SIMPLEX, MOLLUSCUM CONTAGIOSUM, NON-GONOCOCCAL URETHRITIS, TRICHOMONIASIS, and genital warts (see PAPILLOMA), as well as parasitic infestation by lice (‘crab’) or mites (scabies, ‘the itch’). S´ezary syndrome (SS) A cutaneous T-cell lymphoma which resembles – but is distinct from – ADULT T-CELL LEUKAEMIA; HTLV-I provirus has been detected only rarely in SS, and does not appear to be a primary causal agent. The neoplastic T cells in SS may resemble those of ATL, but the nucleus is more commonly cerebriform than multilobed; ATL and SS cells are antigenically distinct and are functionally distinct in vitro [Book ref. 106, pp. 275–284]. SFFV See FRIEND VIRUS and RAUSCHER VIRUS. sfiA, sfiB genes See SOS SYSTEM. SFV SEMLIKI FOREST VIRUS. SG Gower coefficient. In the comparison of two strains by NUMERICAL TAXONOMY: an expression of the degree of similarity in which the comparison involves both simple, discontinuous data (e.g. + and −, or 0 and 1) and continuous (quantitative) data. (cf. entry SSM .) SH-activated cytolysins THIOL-ACTIVATED CYTOLYSINS. SH antigen Syn. HBsAg: see HEPATITIS B VIRUS. shaded matrix In NUMERICAL TAXONOMY: a graphic representation of the interrelationships between the OTUs in a given study. It is a triangular tabulation, the ordinate and abscissa each consisting of a complete list of designations of the OTUs under study; the degree of mutual similarity between the OTUs in any given cluster is indicated by the intensity of shading: the highest degree of similarity corresponds to the darkest shading. 701

shadow-casting shadow-casting See ELECTRON MICROSCOPY (a). shadow yeasts Syn. MIRROR YEASTS. shadowing See ELECTRON MICROSCOPY (a). shake culture (1) A procedure used e.g. for the isolation of anaerobic bacteria. The inoculum is dispersed (by gentle shaking) in a molten agar medium (at ca. 48° C) in a long glass test-tube or a VEILLON TUBE; the agar is allowed to set, and the tube is incubated. An individual colony in the lower (anaerobic) part of the agar can be removed for subculture. (2) A culture in a liquid medium which is continually shaken to ensure aerobiosis in the medium. sharka disease Syn. PLUM POX. sharp eyespot See EYESPOT (sense 2). sheath (1) In SHEATHED BACTERIA: a secreted, tubular structure formed around a chain of cells or around a bundle of filaments; cells may or may not subsequently separate from the sheath. (2) In certain bacteria: a layer of outer membrane covering the flagellum (see FLAGELLUM (a)). (3) See ‘outer sheath’ in SPIROCHAETALES. sheath blight (of rice) CEREAL DISEASES. sheathed bacteria Species of e.g. HALISCOMENOBACTER, LEPTOTHRIX, SPHAEROTILUS, THIOPLOCA and THIOTHRIX which form sheathed trichomes or fascicles. sheathed flagellum See FLAGELLUM (a). sheep cell agglutination test (SCAT) (1) The PAUL–BUNNELL TEST or, in general, any test in which non-sensitized sheep erythrocytes are agglutinated. (2) The ROSE–WAALER TEST. sheep diseases Sheep are susceptible to a wide range of diseases, some of which are specific to sheep. (a) Bacterial diseases: see e.g. ANTHRAX, BLACK DISEASE, BRAXY, BRUCELLOSIS, CAMPYLOBACTERIOSIS, ENZOOTIC ABORTION, FOOT ROT, JOHNE’S DISEASE, JOINT-ILL, LAMB DYSENTERY, LISTERIOSIS, LUMPY WOOL, PULPY KIDNEY, SCALD, STRUCK, SWELLED HEAD, TULARAEMIA; cf. WIMMERA GRASS POISONING. (b) Fungal diseases: see e.g. ASPERGILLOSIS. (c) Mycotoxicoses: see e.g. LUPINOSIS, PASPALUM STAGGERS, PENITREMS, SPORIDESMINS. (d) Viral diseases: see e.g. BLUETONGUE, BORDER DISEASE, CONTAGIOUS PUSTULAR DERMATITIS (sense 1), FOOT AND MOUTH DISEASE, JAAGSIEKTE, LOUPING-ILL, MAEDI, NAIROBI SHEEP DISEASE, PESTE DES PETITS RUMINANTS, RIFT VALLEY FEVER, SHEEP POX, VISNA; cf. SCRAPIE. (See also SHEEP SCAB.) sheep pox (variola ovina) An acute, infectious disease specific to sheep; the causal agent, a Capripoxvirus, appears to infect via abrasions or e.g. by droplet infection. Incubation period: 2 days to 2 weeks. Adult sheep typically develop vesicular, scabforming lesions on the skin; there is no systemic involvement and mortality rates are generally low, but in ewes the disease may predispose towards mastitis if the udder is affected. In lambs (and sometimes in adult sheep) the disease involves e.g. fever, nasal discharge, and the development of lesions on the skin and buccal mucosa and in the alimentary, respiratory and urogenital tracts; mortality rates can be high, and lambs may die even before the skin lesions develop. (cf. GOAT POX.) sheep-pox subgroup See CAPRIPOXVIRUS. sheep scab A (non-microbial) disease caused by bites of the mite Psoroptes ovis; symptoms: itching, skin lesions, and wool shedding. shelf fungi Syn. BRACKET FUNGI. shell (virol.) A term used by some authors to refer to a CAPSID. shell disease (1) Syn. BURNED SPOT DISEASE. (2) See OSTRACOBLABE IMPLEXA. shell vial assay A (qualitative or quantitative) method for detecting human cytomegalovirus (HCMV) in which the specimen

is centrifuged onto a culture of fibroblasts and the preparation subsequently stained with fluorescent monoclonal antibodies specific for the 72 kDa phosphoprotein product (p72) of an immediate-early gene. shellfish diseases See e.g. CRUSTACEAN DISEASES and OYSTER DISEASES. shellfish poisoning A form of FOOD POISONING which results from the consumption of shellfish (molluscs, crustacea) contaminated with toxins or pathogens. Aquatic bivalve molluscs (clams, cockles, mussels, oysters etc) obtain their food by filtering microscopic organisms from the ambient water. Any human pathogens present in the water can thus be concentrated in the bodies of the shellfish and can cause disease when these are eaten by humans. Pathogens transmitted in this way include e.g. HEPATITIS A virus, enteroviruses, ‘parvovirus-like agents’ (see FOOD POISONING (i)), and salmonellae (including S. typhi ); such pathogens typically derive from sewage, whereas Vibrio parahaemolyticus (see FOOD POISONING (h)) is a natural inhabitant of brackish and marine waters. Gastropod molluscs (e.g. whelks, winkles) and crustacea (e.g. lobsters, prawns) are not filter-feeders but may nevertheless become contaminated with pathogens which may be derived from the natural habitat of the animal (as e.g. in the case of V. parahaemolyticus) or may be introduced during the handling and processing of the shellfish (as e.g. in the case of staphylococci). (See also FISH SPOILAGE.) Paralytic shellfish poisoning (PSP, ‘mussel poisoning’) is a severe, often fatal condition resulting from the consumption of shellfish (commonly mussels or clams) which have themselves consumed neurotoxin-forming dinoflagellates (e.g. Gonyaulax spp) and accumulated the toxin(s) – e.g. SAXITOXIN – in their tissues. (See also RED TIDE.) Symptoms of PSP (caused by saxitoxin) typically include diarrhoea, fatigue, and a tingling sensation beginning around the face and spreading to the arms, fingers, and toes; later, numbness may develop, followed by weakness, paralysis, and death (usually within 12 hours) from respiratory paralysis. (cf. CIGUATERA.) sherry See WINE-MAKING. ShET2 enterotoxin See EIEC. Shewanella A genus of bacteria proposed to include Alteromonas hanedai (S. hanedai), A. putrefaciens (S. putrefaciens), and strains of barophilic bacteria (see BAROPHILE) isolated from deepsea waters (S. benthica) [SAAM (1985) 6 171–182; name validation: IJSB (1986) 36 354–356]. (cf. ALTEROMONAS.) shield cell (algol.) See CHAROPHYTES. shift up, shift down (Refers to) a change in (experimental) conditions which causes the growth rate of a microorganism to increase (shift up) or decrease (shift down). Shiga–Kruse bacillus Shigella dysenteriae serotype 1. shiga-like toxins See SHIGA TOXIN. shiga toxin A protein toxin, produced by strains of Shigella dysenteriae, which apparently causes at least some of the symptoms of (bacillary) DYSENTERY; the toxin is cytotoxic in vivo, and is also toxic for some types of cultured cells (e.g. HeLa). The shiga holotoxin consists of an A subunit associated with a pentameric ring of B subunits. The holotoxin binds, via B subunits, to glycolipid receptor sites on the target cell; these receptors – globotriosylceramide (Gb3 ) – are found e.g. in the membrane of endothelial cells (cells that line blood vessels). Shiga toxin is reported to be active against e.g. endothelial cells, colonic/ileal epithelial cells, and B lymphocytes expressing the CD77 ANTIGEN. On uptake of toxin by a cell, the A subunit undergoes proteolytic cleavage, the (catalytic) part of the subunit remaining 702

Sicilian sandfly fever virus [Recommendations on the classification of shigellae: IJSB (1984) 34 87–88.] shigellosis See DYSENTERY (a). (cf. SLEEPY FOAL DISEASE.) shii-take The edible mushroom Lentinula edodes (formerly Lentinus edodes or Cortinellus edodes) traditionally cultivated in Japan. Hardwood logs are inoculated via drill-holes; fruiting, which occurs in spring and autumn, begins after ca. 8 months and may continue for several years. shikimate pathway See Appendix IV (f). Shine–Dalgarno sequence See PROTEIN SYNTHESIS. shingles Syn. HERPES ZOSTER. shipping fever See BOVINE RESPIRATORY DISEASE. shipyard eye Syn. EPIDEMIC KERATOCONJUNCTIVITIS. Shirlan See SALICYLANILIDES. shmoo cell A large, asymmetrical, often pear-shaped yeast cell formed e.g. by the action of a sex PHEROMONE. shock-sensitive transport system Syn. BINDING PROTEIN-DEPENDENT TRANSPORT SYSTEM. shoestrings Syn. boot laces: see ARMILLARIA. Shope fibroma virus See LEPORIPOXVIRUS. Shope papilloma virus See PAPILLOMAVIRUS. short-incubation hepatitis Syn. HEPATITIS A. short patch repair See EXCISION REPAIR. shotgun experiment A CLONING experiment in which the entire genome of an organism is cut into random fragments and cloned (e.g. to generate a genomic LIBRARY). showdomycin A NUCLEOSIDE ANTIBIOTIC which structurally resembles uridine; it inhibits e.g. UMP kinase and other enzymes. shoyu Syn. SOY SAUCE. shufflon A term proposed for a cluster of DNA segments (within e.g. a plasmid) which can invert independently or in groups, resulting in complex rearrangements of the DNA. Such a ‘clustered inversion region’ has been observed in the IncIa plasmid R64; it appears to function as a biological switch, regulating the selection of one of 7 possible open reading frames [NAR (1987) 15 1165–1172]. (cf. RECOMBINATIONAL REGULATION.) Shukla’s method See IMMUNOSORBENT ELECTRON MICROSCOPY. shut-down cell Syn. GROWTH PRECURSOR CELL. shuttle vector (bifunctional vector) A CLONING vector which can replicate in more than one type of organism; e.g., a shuttle vector which can replicate in both Escherichia coli and Saccharomyces cerevisiae can be constructed by linking sequences from an E. coli plasmid with sequences from the yeast 2m plasmid. SHV b-lactamase See b-LACTAMASES. Shwartzman reaction The local Shwartzman reaction involves localized skin necrosis which occurs when an intravenous injection of e.g. ENDOTOXIN (sense 1) is given some hours after an intradermal injection of endotoxin. The generalized Shwartzman reaction (GSR) is a poorly understood, complex syndrome exhibited when a second intravenous injection of endotoxin is given 24 hours after the first; it is characterized by intravascular coagulation and shock. Various mechanisms have been proposed to account for the intravascular coagulation; in one, COMPLEMENT-FIXATION leads to injury of immature PMNs which release factors that promote clotting. In other models macrophages are considered to be the primary cellular effectors. (cf. ENDOTOXIC SHOCK.) sialic acids See NEURAMINIC ACID. sialyl-Lewis x See INFLAMMATION. sib sequence See BACTERIOPHAGE l. sibiromycin See ANTHRAMYCIN. Sicilian sandfly fever virus See PHLEBOVIRUS.

attached temporarily by a disulphide bond – which is later reduced. The catalytic part of the A subunit has N-glycosidase activity: it cleaves a specific adenine residue from the 28S rRNA in eukaryotic ribosomes; this inhibits protein synthesis (by inhibiting the EF-1-mediated binding of tRNA), resulting in cell death. (This mechanism is identical to that of the plant toxin ricin.) [Enteric bacterial toxins (mode of action and relevance to intestinal secretion): MR (1996) 60 167–215.] Shiga-like toxins (verotoxins; verocytotoxins; Vero cell cytotoxins) are produced by so-called enterohaemorrhagic strains of Escherichia coli (see EHEC). These (phage-encoded) toxins are classified as shiga-like toxins I and II (SLT-I, SLT-II); SLT-I is virtually identical to the shiga toxin of Shigella dysenteriae type 1. Note that these toxins are also called ‘shiga toxins’ or ‘Shiga toxins’; thus, with this terminology, SLT-I has been abbreviated to Stx1, and SLT-II to Stx2. There are a number of variant forms of SLT-II, each designated by a lower-case letter. A new variant form of SLT-II (Stx2f) has been isolated from E. coli in the faeces of pigeons (Columba livia) [AEM (2000) 66 1205–1208]. All members of the shiga toxin family appear to share a common membrane receptor site and apparently have the same mode of action. The precise role of these toxins in pathogenesis is uncertain. However, it has been suggested that they may act as vasculotoxins whose primary target is the vascular endothelium. In one model of EHEC pathogenesis, macrophages, adherent at toxin-mediated vascular lesions, are stimulated to secrete certain pro-inflammatory cytokines (TNF-a, IL-1) which upregulate local expression of Gb3 sites – resulting in further toxin binding and exacerbation of vascular damage [TIM (1998) 6 228–233]. (See also STARFISH.) Shiga’s bacillus Shigella dysenteriae serotype 1. Shigella A genus of Gram-negative bacteria of the ENTEROBACTERIACEAE (q.v.). Cells: straight rods, 0.5–1.0 × 1–3 µm, nonmotile. Growth occurs e.g. on nutrient agar, MacConkey’s agar and EMB agar, may or may not occur on more inhibitory media (e.g. DCA, SS agar), and does not occur on KCN media. Sugars are fermented to acid (usually without gas). MR +ve; VP −ve; citrate −ve; H2 S −ve (in TSI); phenylalanine deaminase −ve; lysine decarboxylase −ve. GC%: 49–53. Type species: S. dysenteriae. Shigella spp are intestinal pathogens of man and other primates (see bacillary DYSENTERY); other animals are normally resistant. In animal studies, Shigella is reported to be taken up by the M cells of Peyer’s patches [e.g. TIM (1998) 6 359–365]. S. boydii (= subgroup C). 18 serotypes. Mannitol is fermented, lactose is not. S. dysenteriae (= subgroup A). 12 serotypes. Serotype 1 is catalase −ve and produces SHIGA TOXIN. Mannitol and lactose are (usually) not fermented. S. flexneri (= subgroup B). 6 serotypes. Most strains ferment mannitol but not sucrose or lactose; serotype 6 includes the Newcastle strain (mannitol not fermented, gas produced from glucose), the Manchester strain (acid and gas from glucose and mannitol), and the Boyd 88 strain (acid, no gas, from glucose and mannitol). S. sonnei (= subgroup D). One serotype with two ‘phases’, I and II (resembling the SMOOTH–ROUGH VARIATION of other enterobacteria). Mannitol is fermented; fermentation of lactose and sucrose is detectable after 24 hours. Strains are identified by colicin TYPING. [Book ref. 22, pp. 423–427; serology: Book ref. 68, pp. 113– 142.] 703

sickener sickener See RUSSULA. SID test (vet.) SINGLE INTRADERMAL TEST. SIDD Supercoiling-induced duplex destabilization (= stress-induced duplex destabilization): destabilization (involving strand separation) of a particular region (a SIDD site) in a DNA duplex as a response to a given level of superhelicity. In a model for the activation of the ilvPG promoter in Escherichia coli, destabilization of an upstream SIDD site is counteracted by the binding of INTEGRATION HOST FACTOR close to the site; this causes translocation of superhelical energy to the (downstream) −10 sequence of the promoter – thus facilitating the formation of an open complex and initiating transcription from the promoter [see e.g. Mol. Microbiol. (2001) 39 1109–1115 (1112)]. sideramines (1) Syn. SIDEROPHORES. (2) Syn. hydroxamate SIDEROPHORES. Siderocapsa A genus of IRON BACTERIA. Cells: cocci or coccoid forms which occur singly or in clusters within a common capsule. Type species: S. treubii. siderochromes Syn. SIDEROPHORES. Siderococcus A genus of bacteria found e.g. in soil [see e.g. Book ref. 45, pp. 1049–1059]. sideromycins Iron-chelating ANTIBIOTICS, formed by certain actinomycetes, which are structurally related to hydroxamate SIDEROPHORES; it appears that the iron-chelating part of the molecule permits transport into the target cell, and that the other part of the molecule, which is released by intracellular hydrolysis, is the (as yet uncharacterized) toxic moiety. Sideromycins include albomycin and the ferrimycins – analogues of ferrichrome and ferrioxamine, respectively. siderophilins A family of ferric IRON-chelating glycoproteins which occur in vertebrates: see e.g. LACTOFERRIN and TRANSFERRIN. (cf. FERRITIN; see also SIDEROPHORES.) Certain pathogens (such as Neisseria gonorrhoeae and N. meningitidis) can obtain iron directly from siderophilins [acquisition of transferrin-bound iron by pathogens: Mol. Microbiol. (1994) 14 843–850]; some pathogens (including the species of Neisseria referred to) have cell-surface receptors for human transferrin, and such receptors have been considered as potential targets for VACCINE production. siderophores (syn. ironophores; siderochromes) Low-molecularweight ferric iron-chelating compounds synthesized and exported by most microorganisms for the sequestration and uptake of IRON (q.v.). The two main structural classes of siderophores are catecholamides and hydroxamates; a given organism may produce siderophores of one or both classes. (Typically, iron is bound more tightly by catecholamides than by hydroxamates.) Some siderophores are PLASMID-encoded (see e.g. COLV PLASMID). Catecholamides (‘phenolates’) are derivatives of catechol (o-dihydroxybenzene). One example is enterobactin (= enterochelin): a cyclic trimer of 2,3-dihydroxy-N -benzoyl-Lserine produced e.g. by various enterobacteria; in Escherichia coli it is synthesized by condensation of 2,3-dihydroxybenzoic acid (formed via chorismic acid) with L-serine – the synthesis involving products of genes entA–entG. In E. coli the cellsurface receptor for enterobactin is the FEPA PROTEIN. Parabactin is a catecholamide formed by Paracoccus denitrificans from N 1 ,N 8 -bis(2,3-dihydroxybenzoyl)spermidine (‘compound II’). Vibrio anguillarum forms a novel catechol-type siderophore, anguibactin [characterization of anguibactin: JB (1986) 167 57–65]. Hydroxamates, derivatives of hydroxamic acid (R.CO.NHOH), include aerobactin, a siderophore formed e.g. by various enterobacteria; genes encoding the aerobactin system – the

siderophore itself (iucA–iucD) and its (outer membrane) receptor protein (iutA) – are carried by many COLV PLASMIDS, although the system may also be chromosomally encoded. [Plasmid-specified aerobactin system: Book ref. 161, pp. 741–757; characterization of the iucA and iucC genes: JB (1986) 167 350–355.] The products of the fhuB, fhuC and fhuD genes, located in the cytoplasmic membrane and/or periplasm, may form a binding system for the uptake of iron by aerobactin and other hydroxamate siderophores [JGM (1992) 138 597–603]. In Escherichia coli, the outer membrane receptor for aerobactin, the IutA protein, can also bind CLOACIN DF13. In E. coli, the aerobactin and enterobactin systems can be induced independently [Inf. Immun. (1986) 51 942–947]; both systems apparently require the TONB PROTEIN for transport into the periplasm [JGM (1992) 138 597–603]. Other hydroxamate siderophores include e.g. coprogen (produced by many fungi); ferrichrome (formed e.g. by species of Aspergillus, Neurospora and Ustilago): a cyclic hexapeptide consisting of a glycine tripeptide and a tripeptide of d-N acetyl-L-d-N -hydroxyornithine; ferrioxamines and DESFERRIOXAMINE (formed e.g. by certain bacteria); NOCARDAMINE; and the terregens factor (a growth requirement of e.g. Arthrobacter spp). For extracellular growth, the pathogen Mycobacterium tuberculosis uses a peptide siderophore, EXOCHELIN, and a cell-wallassociated lipophilic compound: MYCOBACTIN; exochelin appears to obtain iron from SIDEROPHILINS and to pass it to mycobactin for internalization. Certain siderophores, e.g. parabactin, have been found to be active, in vitro, against a murine leukaemia cell line and against herpes simplex type 1 virus [TIBS (1986) 11 133–136]. (See also PYOVERDIN.) SIDS SUDDEN INFANT DEATH SYNDROME. sIg Any immunoglobulin at the surface of a B LYMPHOCYTE. sIgA Secretory IgA (see entry IgA). sigatoka disease Syn. BANANA LEAF SPOT. sigF gene See SIGMA FACTOR. sigla Plural of SIGLUM. siglum A designation consisting of letters (particularly initial letters) and/or other characters. Some sigla are acronyms. s (superhelix density) See DNA. s factor (sigma factor) A protein which can bind to a DNAdependent RNA POLYMERASE (RPase) core enzyme and confer on it the ability to initiate TRANSCRIPTION from a particular type of PROMOTER. Cells typically or always encode more than one type of sigma factor, and different types of sigma factor generally confer on the RNA polymerase the ability to transcribe (in vivo) from different promoters; by synthesizing particular type(s) of sigma factor, at appropriate times, the cell can thus control expression of particular gene(s). In Escherichia coli the main sigma factor is s70 (MWt ∼70000) encoded by gene rpoD; an RPase holoenzyme containing s70 (Es70 ) can initiate transcription from most promoters in the E. coli genome – sometimes in association with positive regulatory factors (as e.g. in CATABOLITE REPRESSION). Other sigma factors in E. coli include e.g. s32 (RpoH, formerly HtpR: see HEAT-SHOCK PROTEINS) and s60 (the NtrA protein: see NTR GENES). There are many examples of the way in which the timing of gene expression is controlled by the activity of particular sigma factor(s). In E. coli, assembly of the FLAGELLUM from a number of different proteins is a highly organized process in which components are added in strict sequence – the corresponding genes being expressed in a way that reflects this sequence. 704

signal hypothesis Thus, class III genes are expressed only after genes of classes I and II, and the expression of class III genes depends on synthesis of a sigma factor encoded by the fliA gene; however, even when FliA has been synthesized, this sigma factor is temporarily inactivated by an anti -s factor (FlgM, product of gene flgM ) until the basal body and hook of the flagellum have been completed – completion of the hook apparently acting as a signal that allows release of FlgM and consequent transcription of the class III genes. [Genetic control of flagellar assembly: Cell (1995) 80 525–527.] The E. coli sigma factor ss (encoded by rpoS ) was once associated solely with stationary-phase events but is now known to be involved in the regulation of various responses to stress under log-phase, as well as stationary-phase, conditions [Mol. Microbiol. (1996) 21 887–893]. Under in vitro conditions, either Es70 or Ess can be used for transcription from some promoters, but, in vivo, many promoters exhibit specificity for one of the two holoenzymes – Es70 or Ess ; studies on sigma factor specificity in the osmY gene have indicated that specificity for ss in this gene is influenced strongly (perhaps even determined) by three global regulators – the cAMP–CRP complex (see CATABOLITE REPRESSION), the integration host factor (IHF) and the leucine-responsive regulator protein (Lrp) – which preferentially inhibit Es70 -dependent expression from the osmY promoter [EMBO (2000) 19 3028–3037]. Expression of the rpoS gene is reported to be regulated by the HU PROTEIN [Mol. Microbiol. (2001) 39 1069–1079] and also by a small, novel RNA molecule which interacts with rpoS mRNA and relieves the inhibitory activity of a stem- and-loop structure [Mol. Microbiol. (2001) 39 1382–1394]. In vegetative cells of Bacillus subtilis the major sigma factor is s43 (formerly called s55 ; encoded by gene rpoD); this sigma factor shows some homology with the E. coli s70 and recognizes the same class of promoters. There are also a number of minor sigma factors. A sigma factor may be present at low levels during normal growth but up-regulated under appropriate conditions. For example, sH (encoded by gene spo0H ) is up-regulated during the initiation of sporulation in Bacillus subtilis as a consequence of repression of abrB by Spo0A∼P (see figure (a) in ENDOSPORE). Later in the initiation process, the sporulationspecific sigma factors sE (formerly s29 ; encoded by spoIIG) and sF are synthesized to promote the next stage of sporulation. The Es28 of B. subtilis can initiate transcription at E. coli heat-shock promoters. In B. subtilis, many of the genes and operons so far investigated have two or more overlapping or adjacent promoters which are usually specific for RPase holoenzymes containing different sigma factors; this presumably allows control of gene expression under various conditions and/or during different stages of development. In Mycobacterium tuberculosis, the discovery of a gene (sigF ) [PNAS (1996) 93 2790–2794] encoding a protein homologous to a sporulation-specific sigma factor in Streptomyces coelicolor has provided some evidence in support of the hypothesis that latency (persistence) in this pathogen is associated with the presence of a spore-like state. [Mechanisms of latency in M. tuberculosis: TIM (1998) 6 107–112.] Certain bacteriophages encode sigma factors that are necessary for the expression of some of their genes: see e.g. BACTERIOPHAGE SPO1 and BACTERIOPHAGE T4 (gp55). In some cases, the expression of a sigma factor results from up-regulated translation of its mRNA (rather than increased transcription of the gene). In E. coli, for example, the increase in

s32 following heat shock is due mainly to increased translation of mRNA; translation is up-regulated because the higher temperature destabilizes a secondary structure in the mRNA which, under normal conditions, represses translation [GD (1999) 13 633–636]. Enhancer-dependent sigma factors (s54 ; = sN ). This unique type of sigma factor, once thought to occur only in higher organisms, is found in many species of bacteria (although not in all species [FEMS (2000) 186 1–9]). When bound to a promoter, the s54 -RNA polymerase holoenzyme must be activated by an energy-dependent process before DNA melting (formation of an ‘open complex’, and initiation of transcription) can occur at the promoter. Such activation involves a specialized activator protein which binds to DNA at an enhancer region remote from the promoter – but which can be brought close to the holoenzyme through looping of the intervening DNA; with activator and holoenzyme juxtaposed, the activator’s ATPase activity (triggered e.g. by phosphorylation) provides the energy for localized melting (open complex formation) in the promoter region. (In some cases, DNA looping involves the INTEGRATION HOST FACTOR.) One early example of an enhancer-dependent sigma factor is the rpoN (= ntrA) gene product involved in regulating nitrogen metabolism (see NTR GENES). A more recent example is a s54 regulated operon concerned with the processing of RNA [JBC (1998) 273 25516–25526]. [s54 (minireview): JB (2000) 182 4129–4136.] (See also ANTI-SIGMA FACTOR.) sigma particles See LYTICUM. s structure See ROLLING CIRCLE MECHANISM. sigma virus A probable member of the RHABDOVIRIDAE. Sigma virus infects fruit-flies (Drosophila melanogaster) and is transmitted by the female flies to their offspring. The virus is normally non-pathogenic; however, on brief exposure to CO2 at certain concentrations, infected flies are paralysed and die within a few hours, whereas non-infected flies recover completely. [Sigma virus in cell culture: JGV (1984) 65 91–99.] (See also DROSOPHILA X VIRUS.) sE (AlgU) See ALGINATE. sigmamycin A mixture of TETRACYCLINE and OLEANDOMYCIN. signal amplification (bDNA) See BDNA ASSAY. signal hypothesis The hypothesis that a protein which is destined to pass through (or into) a membrane is synthesized in a precursor form (pre-protein) with a specific N-terminal sequence of amino acid residues (= signal sequence, signal peptide, leader peptide) which is essential for the initiation of translocation and is typically excised (cleaved) during translocation. Translocation in this mode has been demonstrated for many (but not all) secreted and membrane proteins in prokaryotes and eukaryotes; in other cases, protein translocation involves distinct processes which lack the characteristics described above (see later). A signal sequence often consists of several hydrophilic terminal amino acid residues followed by a sequence of >10 predominantly hydrophobic residues and a specific cleavage site; the hydrophobic residues have a tendency to form an a-helix conformation. It is generally assumed that a signal sequence adopts a conformation which spans the membrane and facilitates translocation of the remainder of the polypeptide. [Signal sequences: Mol. Microbiol. (1994) 13 765–773.] In addition to a terminal signal sequence, the pre-protein may incorporate other sequence(s) which ensure that it reaches the correct final destination; for example, a membrane protein (as opposed to a secreted protein) may contain a membrane anchor 705

signal peptidase sequence (= ‘anchor’ or ‘stop transfer’ sequence) that holds the mature protein on or within the correct membrane. Moreover, a protein may undergo post-translational modification to ensure that it is targeted to the correct membrane site (see e.g. BRAUN LIPOPROTEIN). In eukaryotes, secretory proteins (i.e. those to be secreted) – and proteins destined e.g. for the plasma membrane, or for LYSOSOMES – are synthesized on ribosomes of the rough ENDOPLASMIC RETICULUM. Initially, synthesis begins on a free (cytosolic) ribosome, but the newly synthesized (Nterminal) signal sequence binds to a SIGNAL RECOGNITION PARTICLE (SRP) – and this stops polypeptide chain elongation. The ribosome–signal peptide–SRP complex then binds to a ‘docking protein’ at a site on the cytoplasmic surface of the rough endoplasmic reticulum; the SRP is released, and the signal sequence inserts into a transmembrane ‘translocation complex’ such that, on resumption of chain elongation, the nascent polypeptide is translocated through the ER co-translationally – apparently driven mechanically by chain elongation. The signal peptide is excised by an endopeptidase (signal peptidase) whose catalytic site occurs on the lumenfacing side of the ER. Secretion then follows the PALADE PATHWAY. By contrast, most of the proteins destined to enter a MICROBODY (e.g. a PEROXISOME) are synthesized on free (cytosolic) ribosomes without a cleavable signal sequence [BBA (1986) 866 179–203]. [Protein import into organelles (hierarchical targeting signals): Cell (1986) 46 321–322.] In prokaryotes the role of the signal sequence is essentially similar in that its function involves insertion into the transmembrane translocation system. (An earlier view – the ‘membrane trigger’ or ‘trigger’ hypothesis – supposed that the signal peptide confers on the pre-protein the ability to change conformation following contact with the membrane, thus initiating uptake by the membrane.) In Gram-negative bacteria, signal sequence-dependent secretion is involved in type II and type IV forms of PROTEIN SECRETION (q.v.); in type II systems, the secretion of some proteins is mediated by a signal recognition particle (see PROTEIN SECRETION). During, or immediately after, translocation of the protein, the signal sequence is cleaved by an enzyme (signal peptidase); in Escherichia coli, one of the two signal peptidases (leader peptidase; = leader peptidase I ) is active on a wide range of proteins, while the second enzyme (lipoprotein signal peptidase; = signal peptidase II ) is active only on specific, modified proteins (such as the BRAUN LIPOPROTEIN). (In both of these signal peptidases the catalytic site is apparently on the periplasmic side of the cytoplasmic membrane.) Excised signal peptides are degraded by an enzyme (signal peptide peptidase) – e.g. protease IV in E. coli. In some cases the signal sequence is not excised following transmembrane translocation of a protein. One such exception is the export of the TONB PROTEIN to the periplasm in E. coli [JBC (1988) 263 11000–11007]. Secretion that is independent of a cleavable N-terminal signal sequence occurs in type I and type III forms of protein secretion in Gram-negative bacteria. signal peptidase See SIGNAL HYPOTHESIS and PROTEIN SECRETION. signal peptidase II See PROTEIN SECRETION. signal peptide See SIGNAL HYPOTHESIS. signal peptide peptidase See SIGNAL HYPOTHESIS. signal recognition particle (SRP) In eukaryotes: a particle that is involved in translocation of proteins across the endoplasmic

reticulum (see SIGNAL HYPOTHESIS); an SRP contains six polypeptides together with a 7S RNA which is essential for function [Nature (1982) 299 691–698]. In prokaryotes: a particle involved in the translocation of certain proteins across the cytoplasmic membrane (see type II systems in PROTEIN SECRETION). signal sequence See SIGNAL HYPOTHESIS. signal transducers and activators of transcription (STATs) See CYTOKINES. signal transduction pathway See TWO-COMPONENT REGULATORY SYSTEM. signature-tagged mutagenesis A form of TRANSPOSON MUTAGENESIS which can be used to detect those genes, in a pathogen, which are necessary for the pathogen’s growth within the host organism. The principle of signature-tagged mutagenesis is outlined in the figure. (See also IVET.) signet-ring stage (of Plasmodium) See PLASMODIUM. significant bacteriuria BACTERIURIA in which a sample contains potentially pathogenic bacteria in numbers high enough to indicate a URINARY TRACT INFECTION; the numbers of such bacteria must be significantly higher than those which might be expected to occur from contamination of the sample. In the absence of infection, an MSU (taken correctly) should contain no more than ∼104 (commonly ca. 200 g/kg and a good content of soluble, fermentable carbohydrates. (Among common grasses, rye-grasses (Lolium spp) tend to have the highest content of carbohydrate, and cocksfoot (Dactylis glomerata) the lowest.) A silage crop should also have a low buffering capacity (measured e.g. in mE of alkali needed to bring the pH from 4 to 6 in 1 kg DM); a low buffering capacity permits the in-silo pH to drop rapidly, while a high buffering capacity may allow the occurrence of a non-lactic acid fermentation and/or of clostridial spoilage. In e.g. maize (Zea mays) the buffering capacity can be as low as ca. 150–200 mE/kg, while in some grasses, and lucerne (Medicago sativa), it can be up to ca. 500–600 mE/kg; other factors which make maize a good silage crop include its high DM and its content of water-soluble sugars (which can reach e.g. ca. 300 g/kg DM). (A disadvantage of maize is its low content of crude protein; this can be overcome by adding urea – as a source of nitrogen – to the crop at the beginning of ensilage.) Effluents. Effluent from a silo has a high BOD and can cause serious pollution if discharged into streams etc. Factors which affect effluent formation include the DM levels of the ensiled vegetation. [Book ref. 195.] (See also RUMEN.) silent mutation A MUTATION which has no apparent effect on the phenotype of the organism in which it occurs (see also SAMESENSE MUTATION and MIS-SENSE MUTATION). Note that a samesense mutation may not be ‘silent’ if it introduces a detectable CODON BIAS: in Escherichia coli, a synonymous but infrequent (mutant) codon in the leader region of the ompA gene strongly affected in vivo translation, giving rise to a significant reduction in the synthesis of OmpA protein [NAR (1998) 26 4778–4782]. Silent mutations may also affect the results of e.g. DNA-based identification tests [Book ref. 221, pp 16, 172 and 218]. silica deposition vesicle A vesicle, bounded by a unit-type membrane (the silicalemma), present in most – if not all – algae and protozoa which (endogenously) form siliceous structures: e.g. the scales of certain CHRYSOPHYTES, the frustules of DIATOMS, skeletal elements of RADIOLARIA. [Siliceous structures in biological systems: Book ref. 137.] silica gel Hydrated silicon dioxide; silica gel can be prepared in an aqueous, jelly-like form for use e.g. as the basis of a solid MEDIUM. A silica-gel-based medium can be used for the culture of autotrophs (in the complete absence of organic material) and e.g. for testing the ability of heterotrophs to use particular substrates as the sole source of carbon. Powdered silica gel (10 g) is dissolved by heating in 100 ml 7% (wt/vol) aqueous KOH; the solution is dispensed in 20-ml aliquots and autoclaved. To each 20-ml aliquot is added 20 ml of a sterile double-strength liquid nutrient medium, followed by a (pre-determined) volume (ca. 4 ml) of a 20% solution of o-phosphoric acid sufficient to give a

SIGNATURE-TAGGED MUTAGENESIS (continued) Considering the original, mutagenized cells in the ‘input’ pool, the cells of interest are those which, through a (transposon-mediated) mutation, are unable to grow within the test animal, i.e. cells whose virulence has been lowered; such cells will be absent, or few in number, in the ‘recovered’ pool (compared with those cells which were able to grow normally in the test animal). Hence, the signature tags of these ‘virulence-attenuated’ cells will be present in the input pool but absent (or rare) in the recovered pool; consequently, such cells can be identified by hybridization on Replica 1 but an absence of (or weak) hybridization on Replica 2 (see figure). (If ‘dedicated’ tags had been used, virulence-attenuated cells would be identified by the absence of hybridization on a single blot.) In a given ‘virulence-attenuated’ clone, the relevant gene (identifiable from the inserted transposon) can be isolated, cloned and sequenced for further study. Reproduced from Bacteria, 5th edition, Figure 8.22, pages 218–219, Paul Singleton (1999) copyright John Wiley & Sons Ltd, UK (ISBN 0471-98880-4) with permission from the publisher.

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simian T-cell leukaemia virus pH of 7.0. After mixing, the solution is immediately dispensed to Petri dishes. Solidification starts in ca. 1 min and is complete in ca. 15 min. The water of syneresis can be evaporated in an incubator. Incubation of inoculated plates should be carried out in a moist chamber to prevent excessive drying of the medium. silicalemma See SILICA DEPOSITION VESICLE. silicoflagellates A group of unicellular planktonic marine algae of uncertain taxonomic position (formerly included in the Chrysophyceae). (cf. PHYTOMASTIGOPHOREA.) The organisms possess a characteristic net-like, siliceous endoskeleton composed of tubular elements which are often arranged in a polygonal ‘ring’ with supporting struts and projecting spines. The cells each have a single emergent flagellum and many brownish chloroplasts. Present-day genera include Dictyocha. Fossil silicoflagellate skeletons are known from the Late Cretaceous onwards [Book ref. 136, pp. 811–846]. Silicoflagellida See PHYTOMASTIGOPHOREA. silkworm diseases For diseases of the silkworm (Bombyx mori ) see e.g. CYTOPLASMIC POLYHEDROSIS VIRUS GROUP, FLACHERIE, and NOSEMA (p´ ebrine). (See also BEAUVERIA.) silver (as an antimicrobial agent) Silver is a HEAVY METAL which, in elemental or compound form, is typically microbistatic in low concentrations; the functional antimicrobial moiety is the silver ion – which appears to act by binding to e.g. thiol, amine, phosphate and other groups in proteins, nucleic acids and/or other targets. In at least some cases binding is reversible. Antimicrobial agents consisting of metallic or other forms of silver appear to differ primarily in the rate at which they yield silver ions. Gram-positive bacteria are typically much less susceptible than Gram-negative species, and antimicrobial activity can be diminished by non-living organic matter. In bacteria, resistance to silver may be plasmid-borne. Silver nitrate (lunar caustic, AgNO3 ) has astringent properties and may be microbistatic or microbicidal according to concentration; aqueous solutions are used e.g. on dressings for burns (0.5% w/v) and for the treatment of ulcers on mucous membranes (10%). (See also Cred´e procedure in GONORRHOEA.) The silver nitrate pencil is a fused mass containing ca. 98% AgNO3 – together with AgCl and KNO3 – cast in a pencilshaped mould; the moistened tip of the pencil is used e.g. for the cauterization of wounds and the destruction of warts. Ammoniacal silver nitrate has been used in dentistry for the disinfection of tooth cavities. Colloidal silver has been used in medicine (e.g. Colsargen: an isotonic suspension of colloidal silver (0.5%) used for treating mucous surfaces). (See also KATADYN SILVER.) Silver proteinates (e.g. Argyn, Argyrol, Protargin, Protargol ) may be made by precipitating a soluble silver salt, or silver oxide, with protein and then solubilizing with excess protein; they have been used e.g. in various gynaecological preparations. (The antimicrobial activity of a silver proteinate depends on the amount of silver ions it liberates rather than on the proportion of silver in the preparation.) Silver sulphadiazine (1% in an ointment) is used e.g. for the treatment of burns; this compound (which can be bactericidal) releases silver ions, and – unlike AgNO3 – causes blebs in the cell envelope of Pseudomonas aeruginosa. silver dag A suspension of colloidal silver in a quick-drying organic solvent. (See also ELECTRON MICROSCOPY (b).) silver leaf A disease of trees of the Rosaceae (particularly plum trees) caused by Chondrostereum purpureum. Infection occurs via wounds; the fungus grows in the wood, causing discoloration but little or no decay. Infected trees show a characteristic ‘silvering’ of the leaves; this is apparently due to the production of fungal toxin(s) which cause leaf tissues to separate, the

resulting air spaces giving the silvery effect. The fungus itself does not occur in the leaves. silver line system (argyrome) (ciliate protozool.) A regular pattern of lines observed in the superficial layer(s) of silver-stained ciliates; these lines of deposited silver were first described by Klein in the 1920s. While some of the lines appear to coincide with cell-surface detail, others appear to correspond to the locations of certain subpellicular structures. Thus, e.g. the main (most densely staining) lines in Tetrahymena correspond to the rows of kinetosomes which mark the locations of the kineties; these (longitudinal) lines have been termed primary meridia. Other, more weakly staining, lines observed between the primaries, have been termed secondary meridia. Cross-striations have also been observed; some workers believe that lines of deposited silver are formed at the junctions of the pellicular alveoli. (See also KINETY and PELLICLE.) silver–methenamine stain See METHENAMINE–SILVER STAIN. silver scurf A POTATO DISEASE caused by Helminthosporium solani; the skin of the tuber exhibits brown or silver patches which extend on storage. silver stains See e.g. DIETERLE SILVER STAIN; FONTANA’S STAIN; METHENAMINE–SILVER STAIN. (See also SILVER LINE SYSTEM.) silver top (syn. white top) A disease of turf grasses caused by Fusarium poae; the seedheads of infected plants wither before maturing, appearing at first silvery, later white. (cf. WHITEHEAD.) Simbu group See BUNYAVIRUS. simian AIDS (SAIDS) A disease which occurs in macaque monkeys; SAIDS closely resembles human AIDS e.g. in its clinical manifestations, including immune deficiency, progressive depletion of CD4 T cells. The causal agent is a lentivirus, the simian immunodeficiency virus (SIV); SIV differs from the human immunodeficiency virus e.g. in structure and antigenicity of envelope proteins. (Severe immunodeficiency is also caused by a betaretrovirus, the MASON-PFIZER MONKEY VIRUS, but the pathology differs.) Rapid pathogenesis in SAIDS may be accompanied by selection of gp120 variants with decreased ability to bind to CD4 T cells [JV (2002) 76 7903–7909]. [Assay of SIV: JV (2004) 78 5324–5337.] simian foamy virus See SPUMAVIRINAE. simian haemorrhagic fever virus (SHFV) A virus which can cause a fatal haemorrhagic disease in e.g. rhesus monkeys (Macaca mulatta); the natural reservoir of the virus is believed to be the African patas monkey (Erythrocebus patas). SHFV is an enveloped ssRNA virus formerly linked with the family FLAVIVIRIDAE: it resembles flaviviruses e.g. in the 5′ cap structure on the viral RNA [Virol. (1986) 151 146–150], but differs in that at least some of the RNA molecules are polyadenylated [Virol. (1985) 145 350–355]. SHFV has been placed in the arterivirus group (see ARTERIVIRUS). simian immunodeficiency virus See SAIDS. simian malaria See MALARIA. simian parvovirus See ERYTHROVIRUS. simian sarcoma virus (SSV; woolly monkey sarcoma virus) A mammalian type C retrovirus (subfamily ONCOVIRINAE) isolated from a fibrosarcoma in a woolly monkey. It is a replicationdefective, v-onc+ virus which carries the sis oncogene (see SIS). SSV occurs in association with a replication-competent virus – simian sarcoma-associated virus, SSAV – which is serologically related to the GIBBON APE LEUKAEMIA VIRUS; the SSV/SSAV complex can cause fibrosarcomas or fibromas in various monkeys. simian T-cell leukaemia virus (STLV; simian T-lymphotropic virus; primate T-cell leukaemia virus, PTLV) A generic term 709

simian virus 40 single-cell protein (SCP) SCP refers to the cells of microscopic organisms (bacteria, yeasts, moulds or microalgae) grown in large-scale cultures for use primarily as a source of protein in human or animal diets. Although not yet fully exploited commercially, SCP has many advantages over the more conventional sources of protein such as soybean meal and fishmeal. (i) It is rich in protein – ca. 40–85% crude protein, depending e.g. on source; typically, SCP is superior to soybean meal both in protein content and amino acid profile. (Protein content is usually given either as ‘crude protein’, i.e. Kjeldahl nitrogen ×6.25, which includes e.g. nitrogen in nucleic acids, or as ‘true protein’ determined e.g. by the Biuret reaction or by estimation of total amino acids.) (ii) The yield coefficient of SCP, Ys (g cell mass produced/g carbon utilized), is much higher than that of either plants or animals. (iii) SCP can be produced rapidly (owing to the high growth rates of microorganisms) and, unlike agricultural crops, production can be continuous throughout the year – even in countries with little or no agricultural potential or expertise. (iv) A wide range of raw materials, including wastes from other industries, can be used as substrates. In some cases this has the additional advantage of reducing the BOD of certain trade effluents. However, SCP also has disadvantages as a food source. (i) Microbial proteins tend to be deficient in sulphurcontaining amino acids, particularly L-methionine (an essential amino acid for man); this can be overcome by supplementing SCP products with L-methionine or its hydroxy analogue (see HMA). (ii) Some microbial components, e.g. cell walls, cannot be digested by non-ruminant animals or man. (iii) SCP is rich in nucleic acids (ca. 5–15%), mainly RNA. Digestion of purine nucleotides yields uric acid which can be broken down by most mammals; however, man has no uricase, and an intake of more than 2 g nucleic acid per day causes deposition of urates in joints and kidneys, leading to gout and kidney stones. Nucleic acids may be removed e.g. by enzymatic treatment. (iv) Some SCP can affect man adversely in ways not always indicated by animal feeding experiments. Such effects may be due e.g. to residues of toxic substances from the growth medium, or to cell products or components – e.g. fatty acids with odd numbers of carbon atoms (in yeasts grown on hydrocarbons), D-amino acids – usually absent in traditional diets. (v) Cost. Weight for weight, SCP is significantly more expensive than either soybean meal or fishmeal (at least on early cost analyses). A wide range of microorganisms has been evaluated for SCP production, but few are currently used on a commercial scale. Bacteria have advantages such as rapid growth rates and the ability to use a wide range of substrates. They are rich in protein which has a better range of essential amino acids than that found in soybean protein; their content of methionine and cysteine is higher than that of yeasts, although still limiting. However, for human consumption, bacterial SCP needs extensive treatment to remove nucleic acids, LPS etc, and public acceptance is low owing to a tendency to associate bacteria with disease; additionally, the (small) cells are not easy to harvest. Cyanobacteria lack some of these problems (see e.g. SPIRULINA). Yeasts, being larger, are easier to harvest, and they can grow at low pH (reducing the risk of microbial contamination); they have a high content of lysine (an essential amino acid) and have good public acceptability. However, compared with bacteria, yeasts tend to have a lower content of protein and are poorer in methionine. (Yeasts grown primarily for food, rather than for the production of other foods – cf. BAKERS’ YEAST – are called ‘food yeasts’: see e.g. TORULA YEAST.) Mycelial fungi are easy to harvest but they have

for exogenous retroviruses which infect the T cells of monkeys and other subhuman primates. STLV-I (formerly ‘STLV’) is closely related to HTLV-I (see HTLV); it infects Old World monkeys and apes, and can cause lymphomas in e.g. macaques. STLV-III has been isolated from rhesus monkeys (Macaca mulatta) and African green monkeys (Cercopithecus aethiops) and appears to be closely related to the human AIDS virus; a virus similar to STLV-III can apparently infect humans, and it has been suggested that the AIDS virus and STLV-III may have had a common origin [Science (1986) 232 238–243]. (cf. SIMIAN AIDS.) simian virus 40 (SV40; vacuolating agent) A virus of the genus POLYOMAVIRUS. SV40 was originally isolated from kidney cells of the rhesus monkey (Macaca mulatta) and is common (in latent form) in such cells; early polio and adenovirus vaccines prepared in rhesus monkey kidney cells were frequently contaminated with SV40. (See also MASTADENOVIRUS.) In kidney cells from the African green monkey (Cercopithecus aethiops) SV40 causes CPE, including characteristic vacuolation of the cytoplasm. SV40 is usually non-pathogenic in its natural host, but can induce fibrosarcomas and gliomas in newborn rodents (though not in immunocompetent adult animals): see POLYOMAVIRUS for details. similarity matrix See S MATRIX. Simkania negevensis See SPLIT GENE (bacterial). Simmons’ citrate agar KOSER’S CITRATE MEDIUM incorporating BROMTHYMOL BLUE (0.008%) and agar (1.5–2.0%). Simonsiella A genus of GLIDING BACTERIA (see CYTOPHAGALES) which occur in the oral cavity in man and other vertebrates. The organisms are flat filaments (ca. 2–4 µm in length), each composed of elongated cells arranged side-by-side; the outer face of each terminal cell is rounded. Gliding occurs in a direction parallel to the long axis of the filament. Metabolism: chemoorganotrophic. Simonsiellaceae See CYTOPHAGALES. simple matching coefficient See entry SSM . Simplexvirus See ALPHAHERPESVIRINAE. Sin Nombre virus See HANTAVIRUS. SIN virus SINDBIS VIRUS. Sindbis virus (SIN virus) An ALPHAVIRUS which occurs in Africa, Asia, Australia and Europe; it is apparently maintained primarily in birds and is transmitted by mosquitoes which feed on birds (e.g. Culex univattatus in Africa). Other vertebrates can be infected, and the virus is occasionally associated with human illness characterized by arthralgia and a maculopapular rash (‘Sindbis fever’); human diseases caused by Sindbis or related viruses are known as Karelian fever in the former USSR, Ockelbo disease in Sweden, and Pogosta disease in Finland. (See TOGAVIRIDAE for replication cycle etc.) sinefungin An ANTIBIOTIC (obtained from Streptomyces griseolus) which has antifungal, antiprotozoal and antiviral activity; it acts as an analogue of ornithine, inhibiting ornithine decarboxylase and hence putrescine formation. single burst experiment A procedure for studying the lysis of a single cell by a virus (e.g. to determine the BURST SIZE). Essentially, a suspension of cells is infected with viruses and then diluted such that each of a large number of aliquots has a low probability of containing more than one virus-infected cell. Following incubation and lysis, the pfu counts in the aliquots can be statistically analysed e.g. to assess individual burst sizes. The single burst experiment can also be used e.g. to investigate recombination in bacteriophages, genetic analysis being made of the phage progeny from a single bacterial cell coinfected with two genetically distinct phages. 710

single diffusion relatively low growth rates and protein content. Protein from microalgae is inferior, nutritionally, to that of most other microbial sources, and algal SCP has poor acceptability in taste, colour, odour etc. The problem of indigestible algal cell walls may be overcome by cultivating protoplasts or wall-less algae (e.g. Dunaliella [AEM (1976) 31 602–604] and Cosmarium [AEM (1976) 32 436–437]). Production of SCP. Bacteria, yeasts and moulds are generally cultured in well-aerated liquid media in a FERMENTER; typically, the process is continuous (see CONTINUOUS CULTURE) with limiting carbon (C:N less than ca. 10:1) to minimize production of storage compounds such as poly-b-hydroxybutyrate. Algae are grown in batch or semi-continuous culture in ponds with large surface areas. Yeasts and bacteria are harvested by centrifugation; in one process (Pruteen, see later) the bacteria are initially agglutinated so that a more concentrated slurry can be fed to the centrifuge – thus increasing the efficiency of centrifugation. Algae and moulds are harvested by filtration. The concentrated biomass is washed, dried, and used either directly (e.g. in animal feeds) or (for human consumption) its protein content may be extracted and used as a nutrient supplement or as a ‘functional’ ingredient (e.g. to alter the texture of traditional foods). Substrates. The choice of substrate involves considerations such as cost, efficiency of utilization, continuity of supply, and risk of toxic residues. There is, with some exceptions, a good correlation between cell yield and substrate energy content for substrates with heats of combustion up to ca. 11 kcal/g of substrate carbon (approximately that of glycerol); above this value cell yields do not increase [Book ref. 11, pp. 33–34]. (a) High-energy substrates. Hydrocarbons, e.g. natural gas (80–95% methane) and n-alkanes (particularly C10 –C23 ), can be utilized very efficiently by certain bacteria and yeasts, and the risk of microbial contamination is low owing to the inability of most potential contaminants to grow on these substrates. However, hydrocarbons are poorly soluble in (aqueous) growth media, and they may contaminate the final product – although methane, being gaseous, is easily eliminated; the n-alkanes can be used in low concentrations in media containing ammonium salts, phosphate, etc. A further (operational) problem is that hydrocarbon substrates require high rates of oxygenation and heat removal. Organisms which have been grown on hydrocarbons on an industrial scale include yeasts – e.g. Yarrowia lipolytica (= Saccharomycopsis (Candida) lipolytica) – and bacteria (e.g. Pseudomonas spp which utilize waxy residues of crude petroleum); they have been used as animal feeds. (See also HYDROCARBONS and METHANOTROPHY.) [Hydrocarbons as substrates in industrial fermentations: Book ref. 155, pp. 643–683.] Methanol and ethanol are more soluble than hydrocarbons, are readily available in pure form, and are easily removed from the SCP – but they are more expensive. Of organisms grown on methanol, higher yields are given by those which use the RMP PATHWAY rather than the SERINE PATHWAY. One commercial product manufactured in the 1980s, was prepared by growing the obligate methylotroph Methylophilus methylotrophus on methanol in an AIRLIFT FERMENTER. The product (‘Pruteen’) (Imperial Chemical Industries, UK) was marketed (ca. 70000 metric tons annually) as an animal feed, with purified carbon dioxide as a by-product; the process was subsequently discontinued owing to a fall in the price of protein. Owing to the high cost of ethanol, ethanol-derived SCP is likely to be prepared only for human consumption; it includes TORULA YEAST – which has been produced at the rate of over 7000 tons annually by one American company.

(b) Waste products. (i) Molasses (from sugar-refining) is used mainly for growing yeasts (see e.g. BAKERS’ YEAST) but is also used in Taiwan and Japan for growing Chlorella heterotrophically. (ii) Sulphite waste liquor (from paper mills) can be used as a substrate (e.g. for torula yeast) after the hemicellulose has been hydrolysed, by sulphurous acid, to hexoses, pentoses, and acetic, galacturonic and formic acids; sulphite levels are reduced with lime, residual sulphur compounds are removed by steam stripping, and ammonia and various salts are added. In the Pekilo process (Finnish Pulp and Paper Institute), the mould Paecilomyces varioti has been grown in continuous culture and used as animal feed. (iii) Whey (from CHEESE-MAKING) contains ca. 4% lactose which can be utilized efficiently by only a few SCP organisms; the yeast Kluyveromyces marxianus (K. fragilis: ‘fragilis yeast’) is one such organism, ca. 5000 tons of which have been produced annually by one American company. Pilot-scale production of the mould Penicillium verrucosum (P. cyclopium) has been carried out in France. (iv) Starch-rich wastes (e.g. from potato and rice processing) are converted to SCP in the Symba process (Swedish Sugar Corporation) in which one yeast, Saccharomycopsis fibuligera (Endomycopsis fibuligera), produces a- and b-amylases which hydrolyse the starch to glucose and maltose, while a second yeast, Candida utilis, utilizes these sugars to form the bulk of the SCP. This process reduces the BOD of the waste by ca. 90% and thus reduces difficulties in disposal. Cassava starch has been used as a substrate for ‘Cephalosporium eichhorniae’ [AEM (1982) 43 403–411]. (v) Sewage effluents are used for the culture of e.g. Chlorella, Scenedesmus and photosynthetic bacteria (e.g. Rhodopseudomonas capsulata). (c) Renewable sources (e.g. wood and other plant materials). Lignocellulosic materials need pre-treatment to separate the LIGNIN, HEMICELLULOSE and CELLULOSE components. Once free, cellulose can be hydrolysed to fermentable sugars by acid treatment or by CELLULASES (e.g. those from Trichoderma spp). Yeast SCP (Candida sp) has been grown on wood hydrolysates in the former USSR. The future potential of SCP may depend e.g. on advances in technology (such as improved methods for harvesting and protein isolation), on the availability of cheap(er) substrates, and on strain improvement; thus, e.g., the ICI Pruteen strain had improved AMMONIA ASSIMILATION (with consequent improvement in yield) owing to the introduction of the gdh (glutamate dehydrogenase) gene from Escherichia coli [Nature (1980) 287 396–401]. However, other (economic) factors, e.g. the price of ‘conventional’ protein, may be pivotal – although the link between SCP and pollution control may alter the balance of economic viability. single diffusion (serol.) GEL DIFFUSION in which only one component of the system (e.g. antigen) diffuses through the gel – the other component being uniformly pre-distributed throughout the gel. (cf. DOUBLE DIFFUSION.) In the Oudin test (single diffusion, single DIMENSION), antibody is pre-distributed throughout a column of agar (or similar) gel, and a suspension of antigen is layered on top; a band of precipitate forms where the antigen, diffusing downward, meets homologous antibody in OPTIMAL PROPORTIONS. As more antigen reaches the precipitate an ANTIGEN EXCESS occurs at this location and the precipitate dissolves – the zone of equivalence (and the band of precipitate) thus moving down the gel column; the distance moved by the band of precipitate is proportional to the square root of the time taken for the movement. If several different antigen–antibody systems are present, several bands of precipitate will form (and move) independently. 711

single dimension sinusitis Inflammation of one or more of the paranasal sinuses – often a complication of e.g. a COMMON COLD or a tooth infection. Symptoms include pain at the affected site, purulent nasal discharge, and fever. Common causes of acute sinusitis are Haemophilus influenzae or Streptococcus pneumoniae (or both); less commonly, S. pyogenes, Staphylococcus aureus, Branhamella catarrhalis, or anaerobes (e.g. Bacteroides spp) may be involved. siomycin See THIOSTREPTON. siphonaceous (siphonous) Refers to a tubular or vesicular, coenocytic, basically aseptate algal thallus in which the cytoplasm (containing the chloroplasts, nuclei etc) forms a peripheral layer around a large central vacuole. (Septa may separate reproductive structures from the rest of the thallus, and may be formed in response to wounding.) According to species, a siphonaceous thallus may be a simple or branched tube or vesicle (see e.g. BOTRYDIUM and VAUCHERIA); in some algae (e.g. CODIUM) the thallus is made up of a complex combination of such tubes and/or vesicles. (cf. SIPHONOCLADOUS.) siphonein See CAROTENOIDS. siphonocladous Refers to a filamentous algal thallus which is composed of multinucleate cells (as in e.g. CHAETOMORPHA, CLADOPHORA, RHIZOCLONIUM, SIPHONOCLADUS, VALONIA). (cf. SIPHONACEOUS.) Siphonocladus A genus of marine, mainly tropical, siphonocladous green algae (division CHLOROPHYTA) in which the mature thallus is erect with lateral branches. siphonous Syn. SIPHONACEOUS. siphonoxanthin See CAROTENOIDS. sirenin See PHEROMONE. siRNA See RNA INTERFERENCE. sirodesmins See EPIPOLYTHIAPIPERAZINEDIONES. sirohaem A HAEM (sense 1) which is the prosthetic group in e.g. DESULFOVIRIDIN, in the sulphite and nitrite reductases of e.g. Escherichia coli, and in certain IRON–SULPHUR PROTEINS in green plants. Sirolpidium See LAGENIDIALES. SIRS Systemic inflammatory response syndrome: specific symptoms (e.g. temperature >38° C or 12000/mm3 , 10% immature forms) used to define SEPSIS (sense 2) precisely. [Sepsis/SIRS: JAC (1998) 41 (suppl A) 1–112.] SIRS virus See BLUE-EARED PIG DISEASE. sis An ONCOGENE originally identified as the transforming determinant of SIMIAN SARCOMA VIRUS; the v-sis product has an amino acid sequence almost identical to that of human platelet-derived growth factor (PDGF), and may cause transformation by mimicking PDGF [EMBO (1986) 5 1535–1541]. sisomycin 4′ ,5′ -DehydroGENTAMICIN C1a . sister chromatid See CHROMATID. site-directed mutagenesis Syn. SITE-SPECIFIC MUTAGENESIS. site-specific mutagenesis The (in vitro) induction of MUTAGENESIS at a specific site in a given (target) DNA molecule. In one method (D-loop mutagenesis), small fragments of ssDNA, each corresponding to the site to be mutated, are mixed (in vitro) with the full-sized supercoiled dsDNA target molecules in the presence of RecA protein (q.v.) and ATP; under these conditions the fragment invades the dsDNA, generating a single-stranded D-loop which is susceptible to the ssDNAspecific mutagen BISULPHITE. The bisulphite-treated DNA is then introduced into ung − cells (see URACIL-DNA GLYCOSYLASE) by TRANSFORMATION; during a subsequent round of DNA synthesis, the uracil residues (generated from cytosine by the bisulphite) pair with adenine, leading to G·C → A·T transitions.

In the Mancini test (= single radial diffusion test, or single radial immunodiffusion test) – a single diffusion, double dimension method – antibody is pre-distributed uniformly throughout a flat sheet of gel, and the antigen preparation is put into a small, cyclindrical hole (‘well’) cut into the gel sheet; antigen diffuses radially outwards and forms, with the antibody, a halo of precipitate; the area of the circle formed by the halo is proportional to the initial concentration of antigen. single dimension (serol.) See DIMENSION. single intradermal comparative tuberculin test Syn. COMPARATIVE SINGLE INTRADERMAL TUBERCULIN TEST. single intradermal test (vet.) A TUBERCULIN TEST involving an injection of human or bovine tuberculin into an anal fold or into the neck. The test cannot distinguish between infections due to different species of Mycobacterium (cf. COMPARATIVE SINGLE INTRADERMAL TUBERCULIN TEST and STORMONT TEST). single linkage In NUMERICAL TAXONOMY: a method in which two groups (‘clusters’) of OTUs unite (coalesce) at a similarity level determined by the pair of OTUs – one from each cluster – which exhibit the maximum mutual degree of similarity. single radial diffusion test See SINGLE DIFFUSION. single radial immunodiffusion test See SINGLE DIFFUSION. single-site mutation Syn. POINT MUTATION. single-step growth experiment Syn. ONE-STEP GROWTH EXPERIMENT. single-strand binding protein (SSB protein; helix destabilizing protein; ‘unwinding protein’) A class of proteins which bind specifically and cooperatively to ssDNA; they protect the DNA from the action of many nucleases and e.g. can prevent transcription. They have no known enzymic activity, and do not unwind dsDNA. Their roles in the cell are believed to include the stabilization and protection of ssDNA formed e.g. during processes such as DNA replication and DNA repair – although they are now believed to be excluded e.g. during homologous recombination mediated by the RecBCD enzyme. SSB proteins include Escherichia coli binding protein I, phage T4 gp32, phage fd gp5 (see INOVIRUS), and proteins encoded by the F plasmid and other conjugative plasmids. single strand conformation polymorphism See SSCP. single-stranded DNA phage Syn. SSDNA PHAGE. single-vent Petri dish See VENT. singlet oxygen (1 O2 or O12 ) An energized and reactive, but uncharged, form of oxygen which can be toxic to cells. Singlet oxygen may be produced e.g. (i) during ULTRASONICATION; (ii) during the transfer of energy from photoexcited fluorescent dyes to oxygen (see also PHOTODYNAMIC EFFECT); (iii) during the formation of HYDROXYL RADICAL by the reaction between SUPEROXIDE and HYDROGEN PEROXIDE; (iv) during the reaction between hypohalite and H2 O2 (see also MYELOPEROXIDASE). (Some of the oxygen produced during the spontaneous, i.e. non-enzymatic, dismutation of superoxide has been reported to be singlet oxygen.) Singlet oxygen is quenched e.g. by CAROTENOIDS. sinI gene See ENDOSPORE (figure (a) legend). Sinorhizobium meliloti See OSMOREGULATION. sintered glass filter See FILTRATION. sinuate (1) Wavy; undulating. (2) (syn. emarginate) In an agaric: refers to a LAMELLA in which the lower edge is notched at its junction with the stipe. Sinuolinea See MYXOSPOREA. sinus Any groove, constriction or cavity in an organism or cell: see e.g. placoderm DESMIDS. 712

skin microflora same or different molecules, with no synthesis or degradation of DNA – and without hydrolysis of phosphodiester bonds (i.e. the reaction is independent of ATP and other energy sources). The initial juxtaposition (synapse) of the sequences involves DNAbinding proteins; the two sequences are often identical, but in some cases (e.g. the attB and attP sites in phage l integration) they are dissimilar. Cuts are made at staggered sites in the two strands of a given duplex, either concurrently or sequentially, and similar cuts are made in the juxtaposed duplex; strand exchange, between the duplexes, is followed by ligation. Each particular type of SSR system involves a protein (a recombinase) which recognizes specific sequences and appears to mediate cutting, strand exchange and ligation; as well as a recombinase, accessory proteins (e.g. the HU PROTEIN) may be needed. Recombinases are of two main types. One type is exemplified by Tn3 resolvase (see TN3), the other by phage l integrase [TIG (1992) 8 432–439, and erratum in TIG (1993) 9 45]. A resolvase-type recombinase (encoded e.g. by Tn3, Tn21 and Tn552 ) forms an intermediate in which all four strands are cut concurrently, with 5′ phosphate bound to recombinase. (Phosphate–protein binding conserves energy for subsequent ligation.) The integrase-type recombinase (e.g. l Int, and the lox /Cre system of BACTERIOPHAGE P1) cuts/joins strands pairwise; this enzyme forms an intermediate equivalent to a Holliday junction (see RECOMBINATION) in which only one pair of strands has been exchanged. Examples of SSR include: integration/excision of BACTERIOPHAGE l (q.v.); RECOMBINATIONAL REGULATION systems of Salmonella and phage Mu; lox /Cre in BACTERIOPHAGE P1; the resolvase of Tn3 (q.v.) and other transposable elements; gene splicing; monomerization of plasmid dimers; some cases of plasmid–chromosome interaction [JB (1992) 174 7495–7499]; and insertion of the gene cassette into an integron [JAC (1999) 43 1–4]. Some authors regard transposition as a form of (nonconservative) site-specific recombination. sitophilous Living or growing on food (especially cooked or prepared food). Sivatoshella See EIMERIORINA. sixth disease Syn. EXANTHEM SUBITUM. SJ Jaccard coefficient (sometimes spelt Jacquard coefficient). In NUMERICAL TAXONOMY: a coefficient which is similar to SSM (q.v.) but which is calculated on the basis of matching positive characteristics; if a given characteristic is negative in both OTUs it is discounted. skeletal hyphae See HYPHA. Skeletonema See DIATOMS. skiaphilic (skiaphilous) Shade-loving. skin microflora Human skin is a relatively hostile environment for most microorganisms due e.g. to its low aw and the presence of antimicrobial fatty acids released from sebum by the resident flora. Resident bacteria normally include staphylococci (e.g. S. epidermidis) and Propionibacterium acnes; these organisms generally occur in scattered colonies on the skin and in the pilosebaceous follicles [JGM (1984) 130 797–801; 803–807]. (See also ACNE.) Other organisms commonly present on skin include yeasts (e.g. Malassezia spp), aerobic coryneforms, and micrococci. Transient organisms depend e.g. on standards of personal hygiene, and may include coliforms, streptococci, pseudomonads etc. A reduction in the numbers of microorganisms on the skin may be desirable for various reasons (e.g. to prevent wound

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A T

G C

SITE-SPECIFIC MUTAGENESIS (oligonucleotide-directed mutagenesis) (diagrammatic). Here, a phage M13 cloning vector is being used to create a point mutation at a known site in a given gene. The purpose of phage M13 is to make single-stranded copies of the relevant gene. Initially, the (double-stranded) gene is inserted into a circular, doublestranded form of the M13 genome – the so-called replicative form (an intermediate stage in phage replication); during the final stage of replication (in a bacterium), M13 produces ccc ssDNA genomes, each genome incorporating one single-stranded copy of the target gene. The diagram (top) shows one single-stranded phage M13 genome. Within the M13 genome, a 20-nucleotide sequence of the target gene (its size exaggerated for clarity) is shown between two bars. Within this sequence of the target gene we wish to replace deoxythymidine (T) with deoxycytidine (C). The first step is to synthesize an oligonucleotide that is complementary to the 20-nucleotide sequence of the target gene – except for one mismatch at the required site: deoxyguanosine (G) opposite deoxythymidine (T). Each of the synthesized oligonucleotides is then bound to a copy of the target gene (top) and used to prime in vitro DNA synthesis (dashed line, centre); subsequent ligation results in dsDNA molecules, each containing the single mismatch in the target gene. These dsDNA molecules are inserted into bacteria by transformation; within the bacteria, replication of the molecules will segregate mutant molecules (bottom, right) and non-mutant molecules (bottom, left). Reproduced from Bacteria 5th edition, Figure 8.20, page 215, Paul Singleton (1999) copyright John Wiley & Sons Ltd, UK (ISBN 0471-98880-4) with permission from the publisher.

Another method involves the use of a chemically synthesized oligonucleotide containing the desired mutant base sequence; this method (oligonucleotide-directed mutagenesis) is outlined in the figure. site-specific recombination (SSR) RECOMBINATION involving CROSSING OVER between short, specific dsDNA sequences, in the 713

skin substantivity infection, body odour etc) and may be achieved by washing or by treatment with ANTISEPTICS. Washing with SOAPS may remove large numbers of organisms, particularly Gram-negative bacteria, but may simply redistribute the resident microflora; organisms in pilosebaceous follicles are almost impossible to eliminate entirely. ‘Body odour’ is due to the metabolism of apocrine sweat gland secretions by the skin microflora with the formation of malodorous substances (e.g. amines); this can be countered by washing and by the use of deodorants containing aluminium salts (to inhibit sweating) and antiseptics to inhibit microbial action. skin substantivity The extent to which a residue of an antiseptic remains on the skin after washing with a soap containing that antiseptic. skin test Any test in which an antigenic preparation (derived e.g. from a pathogen) is injected into the skin, or applied to the surface of the skin (a patch test), and in which the ensuing reaction (if any) may be used e.g. to assist in a medical diagnosis, to indicate susceptibility to a given disease, or to detect an allergy. (See e.g. BRUCELLIN TEST; DICK TEST; FREI TEST; HISTOPLASMIN TEST; LEPROMIN TEST; SCHICK TEST; TUBERCULIN TEST; VOLLMER PATCH TEST.) skin tuberculosis A chronic disease of cattle in which hard lesions develop in the skin, often on the legs. Acid-fast organisms are often found in the lesions, but the aetiology is uncertain. Affected animals may react to tuberculin (see COMPARATIVE SINGLE INTRADERMAL TUBERCULIN TEST). Skrjabinella See EIMERIORINA. Skulachev ions See CHEMIOSMOSIS. s.l. SENSU LATO (q.v.). slaframine A parasympathomimetic alkaloid MYCOTOXIN produced by Rhizoctonia leguminicola, a fungus which causes ‘blackpatch disease’ of red clover; consumption of the infected red clover by livestock results in a MYCOTOXICOSIS characterized by excessive salivation (‘slobber syndrome’) and feed refusal. Slaframine itself has no biological activity but it is converted in the liver to an active form which, chemically and physiologically, closely resembles acetylcholine. (The active form can also be generated photochemically in the presence of FMN.) slant Syn. SLOPE. slapped cheek syndrome Syn. ERYTHEMA INFECTIOSUM. sleeping sickness (African trypanosomiasis) A human TRYPANOSOMIASIS which occurs in Africa and which is transmitted by species of GLOSSINA. The causal agent is Trypanosoma (Trypanozoon) brucei gambiense (in West and West Central Africa, and sometimes also in e.g. Sudan and Uganda), or T. (T.) brucei rhodesiense (mainly in East Africa, from Ethiopia to Botswana); the disease caused by T. (T.) b. rhodesiense tends to be more acute. [See book ref. 72, pp 97–128.] Weeks or months after the initial infected bite there is an irregular, recurrent fever, enlargement of lymph nodes (see also WINTERBOTTOM’S SIGN), malaise, joint pains and loss of weight; later symptoms may include e.g. insomnia or drowsiness, epileptic attacks and coma. The disease is usually fatal if untreated. Lab. diagnosis: e.g. microscopy of thick blood smears, lymph node aspirate or cerebrospinal fluid (CSF); MAECT; serological methods – e.g. an indirect fluorescent antibody test. Chemotherapy. SURAMIN has been used in the early stages of the disease when there is no CNS involvement; in later stages (when the CNS is involved) agents such as melarsoprol (see ARSENIC) and eflornithine are used because they can pass the blood–brain barrier.

Eflornithine (DL-a-difluoromethylornithine; DFMO) is used against Trypanosoma (T.) brucei gambiense but is not effective against T. (T.) brucei rhodesiense; this agent inhibits the enzyme ornithine decarboxylase (ODC), thus inhibiting the synthesis of trypanothione (see ARSENIC). The ability of eflornithine to act therapeutically may depend on a slow turnover of trypanosomal ODC (relative to that of mammalian ODC); this appears to be the case with a cattle-infecting trypanosome [JBC (1990) 265 11823–11826]. Eflornithine is useful in late-stage trypanosomiasis as it readily enters the CSF. sleepy foal disease (‘shigellosis’) An acute, usually fatal, septicaemic disease of newborn foals, caused by Actinobacillus equuli. Infection may occur in utero or postnatally. slide (microscope slide) A piece of flat, transparent, colourless glass, about 75 × 25 × 1 mm, on which a specimen is placed (or a SMEAR made) for microscopical examination; the specimen may be overlaid with a COVER-GLASS. (The slide plus its specimen is also referred to as a ‘slide’.) A suitably prepared specimen (e.g. a fixed, dehydrated, cleared section of tissue) may be made permanent by mounting it (e.g. in CANADA BALSAM) and overlaying it with a cover-glass; when dry, the balsam cements cover-glass to slide. (cf. CAVITY SLIDE, RING SLIDE.) slide agglutination test Any agglutination test in which antigen and antibody preparations are mixed and allowed to interact on the surface of a slide; one or more dilutions of the antigen and/or antibody preparations may be used in the test – a given dilution reacting with a standard amount of the other reactant. Such tests are generally used only when detectable agglutination occurs within minutes. (Agglutination may be detected e.g. by lowpower microscopical examination.) slim disease In Africa: the name for a condition characterized by a profound loss of weight and constant diarrhoea; the condition is commonly (or always) AIDS. slime bacteria Bacteria of the MYXOBACTERALES. slime layer See CAPSULE. slime moulds A category of eukaryotic organisms which typically have some fungus-like attributes (e.g., the production of spores in or on fruiting bodies) and some animal-like attributes (e.g., a phagocytic, amoeboid vegetative phase); as commonly used, the term ‘slime moulds’ refers specifically to the socalled ‘true’ or acellular slime moulds (see MYXOMYCETES) and the CELLULAR SLIME MOULDS. Taxonomically, these organisms are variously classified – together with certain other groups of organisms – as fungi (division MYXOMYCOTA), as protozoa (mostly in classes of the RHIZOPODA – the labyrinthulas and thraustochytrids being placed in a separate phylum, Labyrinthomorpha), or as a distinct phylum (GYMNOMYXA) of the kingdom PROTISTA (sense 2). slimicide An antimicrobial agent used to inhibit slime-forming organisms. slipper animalcule The ciliate Paramecium. slit sampler Any instrument, used for sampling the airborne microflora, in which AIR is drawn in through a narrow slit onto an adhesive collecting surface – see e.g. HIRST SPORE TRAP. slobber syndrome (vet.) See SLAFRAMINE. slope (slant) (1) A solid medium which has been allowed to set (in the case of e.g. agar or gelatin media) or which has been inspissated (in the case of e.g. DORSET’S EGG) in a diagonally oriented test-tube or bottle. (See also BUTT and POTATO SLOPE.) (2) A CULTURE prepared by the inoculation and incubation of a slope (sense 1). sloppy agar (semi-solid agar) See AGAR and MEDIUM. slow-cycling rhodopsin (SCR) A RETINAL-containing protein, small amounts of which have been detected in some of the strains 714

smoking from caliciviruses. Sequencing data also show that SRSVs are genetically diverse. Phylogenetic analysis indicates at least two genogroups, each consisting of a number of genotypes; for example, Norwalk virus, Southampton virus and Desert Shield virus comprise genogroup 1, while three clusters (one consisting of Hawii virus and Melksham virus) form genogroup 2. [SRSVs (review): RMM (1997) 8 149–155.] small T antigen See POLYOMAVIRUS. smallpox (variola major) An acute infectious human disease caused by the variola major virus (see VARIOLA VIRUS). Infection occurs by droplet inhalation and by direct contact with infected persons or fomites. (Contaminated clothing, scabs etc can remain infective for years.) Incubation period: 7–17 days. Typically, symptoms begin abruptly, with fever, headache, nausea, and muscle and joint pains; 2–4 days later the characteristic skin lesions appear. The lesions are most numerous on exposed parts of the body (face, hands etc); they begin as macules, becoming vesicular, then pustular, finally drying to form thick crusts which eventually drop off, leaving scars (pockmarks). The disease may be fatal; recovery is followed by long-term immunity. Other forms of the disease occur. Haemorrhagic smallpox is the most severe, with generalized haemorrhages and mortality rates of ca. 100%. Variola sine eruptione is a mild, feverish illness (without skin lesions) resembling the prodromal stage of classical smallpox; it occurs mainly in vaccinated individuals. Alastrim (variola minor, Kaffir pox, amaas) is a mild form resembling classical smallpox; it is caused by the variola minor virus. Complications of smallpox include e.g. secondary bacterial infection of skin lesions followed by septicaemia; lesions in the eyes may lead to blindness. Lab. diagnosis: identification and/or culture of the virus from vesicle fluid, smears from skin lesions etc (see also GUARNIERI BODIES); serological tests (e.g. precipitin test, CFT). Vaccines against smallpox contain live VACCINIA VIRUS which is injected into the skin to establish a localized viral infection in which a smallpox-like lesion forms at the vaccination site. Complications of vaccination include e.g. eczema vaccinatum (see ECZEMA), post-vaccinal ENCEPHALITIS, and generalized vaccinia. Immunity induced by vaccination wanes after several years, although an allergic sensitivity to viral proteins may persist. In the past, smallpox occurred in epidemics and pandemics throughout the world, with enormous suffering and loss of life. A world-wide eradication programme (based on vaccination, isolation of cases etc), launched by the WHO in 1967, has led to the complete extinction of the disease in nature – the first disease to have been conquered on a global scale. The last recorded naturally acquired cases occurred in October 1975 (variola major) and October 1977 (variola minor). Eradication was possible since there is no asymptomatic human carrier state and apparently no animal reservoir (cf. MONKEYPOX). Smc protein See CELL CYCLE (b). smear (film) Any material (e.g. bacterial culture, wound exudate) prepared for microscopical examination as a thin film on a SLIDE; a smear is often dried, fixed (see e.g. FLAMING), and stained prior to microscopical examination. SMEDI viruses See ENTEROVIRUS. smf SODIUM MOTIVE FORCE. smoking (of meats, fish) A method of FOOD PRESERVATION in which the foodstuff is exposed to smoke for hours or days; smoking has a drying effect, lowering the WATER ACTIVITY and raising the salt concentration of the food. Wood smoke contains various phenolic, cresylic and aldehyde components which have antibacterial and antifungal properties.

of Halobacterium salinarium which contain a PURPLE MEMBRANE. On illumination with yellow light, a 375-nm-absorbing form of SCR accumulates, while illumination with blue (or near-UV) light causes an accumulation of a 590-nm-absorbing form. It has been suggested that SCR may act as the photosensitive pigment during PHOTOTAXIS in halobacteria. slow disease (slow virus infection) An infectious human or animal disease which is characterized by a long, usually asymptomatic, incubation period (months or years) and a prolonged, progressive course, usually or always ending in death. See e.g. PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY, SUBACUTE SCLEROSING PANENCEPHALITIS and VISNA. [Pathogenesis of slow virus diseases: JID (1986) 153 441–447.] (See also LATENT INFECTION and PERSISTENCE.) ‘Unconventional slow virus infections’ was the former name for the PRION-mediated TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES. slow-opsin See OPSIN. slow sand filter See WATER SUPPLIES. slow virus (1) A virus of the LENTIVIRINAE. (2) Any virus (or subviral agent) responsible for a SLOW DISEASE in man or animals. SLT-I See SHIGA TOXIN. SLT-II See SHIGA TOXIN. sludge gas See ANAEROBIC DIGESTION. slug (of slime moulds) See DICTYOSTELIUM. SM medium A medium widely used for the culture of cellular slime moulds (e.g. DICTYOSTELIUM). SM medium generally contains (w/v) peptone (1%); D-glucose or lactose (1%); Na2 HPO4 .12H2 O (0.1%); KH2 PO4 (0.15%); agar (2%). The pH is adjusted to 6.5. Other ingredients – e.g. yeast extract (0.1%) and MgSO4 (0.05%) – may be added. The medium is inoculated with suitable prey (e.g. Escherichia coli ) and with spores or myxamoebae of the slime mould; incubation is commonly carried out at ca. 20–25° C. [Cultivation of dictyostelids: Book ref. 144, pp. 48–86.] SmaI A RESTRICTION ENDONUCLEASE from Serratia marcescens; CCC/GGG. SMAC medium See EHEC. small cytoplasmic RNA See SCRNA. small iridescent insect viruses See IRIDOVIRUS. small nuclear RNA See SNRNA. small round structured viruses (SRSVs) A heterogenous group of small (∼20–40 nm) viruses that include common causal agents of food-borne and water-borne diarrhoeal disease/gastroenteritis; the name SRSVs reflects their appearance under the electron microscope. Viruses with this description have been referred to as e.g. ASTROVIRUSES, human caliciviruses (HCVs) and parvo-like viruses; many have been named after the location of particular outbreaks of disease – e.g. NORWALK VIRUS. Because the SRSVs have not been cultured, most of the information about them has come from epidemiological studies, studies with volunteers, and laboratory investigations – the latter relying heavily on electron microscopy. Specialized applications of electron microscopy that have been useful include immunoelectron microscopy (IEM) (in which viruses and antibodies react in the fluid phase), and solid-phase immunoelectron microscopy (SPIEM) (in which viruses are captured by gridbound antibodies). SRSVs have a genome of positive-sense ssRNA (∼7.5 kb in several which have been sequenced). They have been classified in the CALICIVIRIDAE; however, comparison of the sequence and genome organization of Manchester virus (a calicivirus) with those of SRSVs suggests that SRSVs are taxonomically distinct 715

smooth endoplasmic reticulum smooth endoplasmic reticulum See ENDOPLASMIC RETICULUM. smooth–rough variation (S→R variation) In many types of (Gram-positive and Gram-negative) bacteria: a change in cellsurface composition which occurs spontaneously during in vitro or in vivo growth. Some types of S→R variation are reversible; in some cases reversion from the rough to the smooth condition occurs if the rough strain is grown in a living animal. In a number of cases S→R variation appears to involve selection of mutants. S→R variation was first recorded in the enterobacteria. In these organisms, smooth (glossy) colonies may be formed on primary isolation, and rough (dull) colonies may develop on subculture; however, because cell-surface components differ widely in different bacteria, the colonies of strains designated ‘smooth’ or ‘rough’ do not always conform to this description. In pathogenic bacteria an S→R transition is, by definition, associated with a lowering of virulence; thus, e.g. smooth (capsulated) strains of Streptococcus pneumoniae are virulent, whereas rough (non-capsulated) strains are found to be avirulent in experimental animals. In general, an S→R transition involves some or all of the following changes:

(2) Plant diseases caused by the smut fungi (Ustilaginales); those caused by members of the Tilletiaceae on cereals are called ‘stinking smuts’ or bunts (see e.g. COMMON BUNT and KARNAL BUNT). In covered smuts of cereals, the smut sori remain intact within the glumes, so that the spores are not normally released until the grain is threshed; in loose smuts, disruption of the host’s tissues by the sori permit the spores to be easily dispersed by wind etc. Some smut fungi incite GALLS in the host plant. Covered smuts on barley and oats are caused by Ustilago hordei (formerly U. kolleri on oats) and are characterized by blackened ears and (often) the absence of awns; control: antifungal seed treatment. Loose smuts of barley and wheat are caused by (different strains of) U. nuda and are characterized by the development of powdery masses of black spores in place of the grains – diseased ears emerging slightly early, and the stems which bear them often being taller than normal stems; the dispersed spores can infect healthy grain which, if used as seed grain, perpetuates the disease. Loose smut was once controlled by immersing seed grain in warm water (e.g. 49° C for 1.5 hours); it is now controlled by the use of certified (pathogenfree) seed grain or by the use of a systemic antifungal agent (e.g. CARBOXIN). Common smut of maize is caused by U. maydis and is characterized by the development of whitish, glistening galls on various parts of the plant (including the ears); the galls rupture to release a mass of black spores. SnaBI See RESTRICTION ENDONUCLEASE (table). SNAP-25 See TETANOSPASMIN. snap-freezing Syn. QUENCH-FREEZING. snow algae See e.g. RED SNOW. snow blight A disease of Scots pine and other conifers caused by Phacidium infestans. It occurs in regions of prolonged deep snow cover, the fungus apparently spreading among the needles of young trees under snow; in spring the affected needles turn brown and fall. snow mould Any of several fungi which cause disease in various winter-sown crop plants, developing preferentially under a cover of snow. Common examples: Fusarium nivale, which can cause a severe disease in winter-sown cereals such as wheat and rye (sometimes causing complete crop loss), and Typhula spp which can cause disease (‘snow rot’, ‘typhula blight’) in snow-covered turf-grasses and cereals. (The term ‘snow mould’ is sometimes used specifically for F. nivale.) Snow Mountain agent (SMA) A Norwalk-like virus (see NORWALK VIRUS) which can cause acute gastroenteritis in humans. [RIA for the detection of SMA: JMV (1986) 19 11–18.] snow rot See SNOW MOULD. snowshoe hare virus See BUNYAVIRUS. SNP Single-nucleotide polymorphism. SNPV See NUCLEAR POLYHEDROSIS VIRUSES. snRNA Small nuclear RNA. The eukaryotic nucleus contains numerous small RNA molecules which are typically 300 nt long), but are generally much less numerous than the metazoan U-RNAs.

(a) the formation of colonies of altered appearance; (b) loss of specific smooth-strain antigens and (hence) loss of agglutinability in specific antiserum; (c) an increase in cell-surface hydrophobicity; (d) an increased susceptibility to hydrophobic antibacterial agents; (e) an increased susceptibility to phagocytosis; (f) an increased autoagglutinability in saline; (g) altered suceptibility to certain phage(s) and bacteriocin(s); (h) loss of, or reduction in, virulence. Enterobacterial smooth (S) strains are those in which the cell wall LIPOPOLYSACCHARIDES are entire, i.e. they include the (complete) O-specific chains. In semi-rough (SR) mutants only one oligosaccharide subunit is present – such strains apparently lacking the ability to polymerize the (normally repeating) subunits of the O-specific chains. In rough (R) mutants the Ospecific chains are lacking altogether; such strains are deficient in antigenic specificity (see O ANTIGEN) because their cell-surface constituents (core oligosaccharide + lipid A) may be similar or identical to those in organisms of related species or genera. In some mutants, not only is the O-specific chain missing, but part of the core oligosaccharide is also missing; such mutants are referred to as deep roughs. In Salmonella typhimurium, rough mutants designated Ra, Rc, Rd1 , Rd2 and Re strains lack, respectively, the O-specific chain, terminal glucose and galactose residues, the proximal glucose residue, the distal heptose residue, and the proximal heptose residue of the core oligosaccharide (see figure in entry LIPOPOLYSACCHARIDE). Because rough strains fail to agglutinate with anti-O antisera, smooth strains of enterobacteria are used in agglutination tests. Smooth strain See SMOOTH–ROUGH VARIATION. SMP Submitochondrial particle: see ETP. smudge A disease of e.g. onions (mainly white varieties) and leeks caused by Colletotrichum circinans. Fungal stromata form dark patches on the bulb; in wet conditions the stromata may form a mass of conidiophores. (See also ONION ROT.) smut fungi See USTILAGINALES. smut spores See USTILAGINALES. smuts (1) Fungi of the order USTILAGINALES, particularly those of the family Ustilaginaceae. 716

soft rot snRNAs function in the nucleus in the form of ‘small nuclear ribonucleoprotein particles’ (snRNPs or snurps). Some proteins are common to several snurps, and some snurps contain more than one snRNA (e.g. U4 and U6 both occur – apparently basepaired together – in the same snurp). Snurps are believed to play important roles in mediating and regulating post-transcriptional RNA processing events: e.g. the splicing of introns from nuclear pre-mRNA (see SPLIT GENE (a)). [Nature (1985) 316 105–106; functions for snRNAs in yeast: TIBS (1986) 11 430–434; conservation of U-snRNPs in fungi, plants and vertebrates: EMBO (1987) 6 469–476.] (cf. SCRNA.) snRNP See SNRNA. snurp See SNRNA. Snyder–Theilen feline sarcoma virus See FES. soaps (as antimicrobial agents) In general, soaps (sodium or potassium salts of long-chain fatty acids) have little or no intrinsic antimicrobial activity, but their surfactant properties can help to reduce the number of microorganisms on the skin. Some soaps are given positive antimicrobial properties by the incorporation of certain antiseptics (see e.g. BISPHENOLS); carbolic soap contains phenol, and some antiseptic soaps contain TCC (see CARBANILIDES). Critical concentrations of soap are needed for the activity of some disinfectants (e.g. Lysol – see PHENOLS). Some antimicrobial agents (e.g. QUATERNARY AMMONIUM COMPOUNDS) may be inactivated by soaps. SOB system See SOS SYSTEM. sobemoviruses (southern bean mosaic virus group) A group of ssRNA-containing PLANT VIRUSES, each of which has a relatively narrow host range; transmission occurs via beetles, via seeds (in some hosts), and mechanically. Type member: southern bean mosaic virus (SBMV); other member: turnip rosette virus. Possible members include e.g. blueberry shoestring virus, cocksfoot mottle virus, and rice yellow mottle virus. Virion: icosahedral (ca. 30 nm diam.) stabilized by divalent cations. The structure of SBMV is similar to that of TOMBUSVIRUSES, but the coat protein (MWt ca. 30000) lacks a P domain. Genome: one molecule of linear positive-sense ssRNA (MWt ca. 1.4 × 106 ); the 3′ end is neither polyadenylated nor tRNA-like, and the 5′ end is associated (in SBMV and TRV) with a small protein which is necessary for infectivity. Virions occur in both nucleus and cytoplasm in infected plant cells, sometimes forming crystalline arrays in the cytoplasm. SOD SUPEROXIDE DISMUTASE. Sodalis A genus of Gram-negative bacteria of the family Enterobacteriaceae which occur as intra- and intercellular symbionts in various tissues of the tsetse fly (GLOSSINA) (but which can also be grown in vitro). Studies on the genome of S. glossinidius have indicated that, compared with the genome of Escherichia coli, many of the genes concerned with energy metabolism and with the assimilation of carbon compounds appear to be missing; it was suggested that this may indicate an adaptatin to the use of those energy sources which are available in blood [genome size and coding capacity of S. glossinidius: JB (2001) 183 4517–4525]. (See also WIGGLESWORTHIA and WOLBACHIA.) sodium azide See AZIDE. sodium dodecyl sulphate See SDS-PAGE. sodium motive force (smf) The energy associated with a transmembrane electrochemical gradient of sodium ions; smf is analogous to proton motive force (pmf) (see CHEMIOSMOSIS). In some organisms smf is generated by Na+ /H+ antiport and is used as a driving force for certain TRANSPORT SYSTEMS; for example, the Na+ / melibiose symport system is used by

Escherichia coli for uptake of the sugar melibiose – melibiose being transported together with sodium ions (i.e. transport at the expense of smf); in such cases smf is secondary to (i.e. dependent on) pmf. (See also ION TRANSPORT.) The marine bacterium Vibrio alginolyticus can generate smf by a primary sodium pump: in this organism respiration can be directly coupled to the outward pumping of sodium ions at the NADH–quinone oxidoreductase segment of the respiratory chain; smf thus generated is insensitive to PROTON TRANSLOCATORS such as CCCP. In V. alginolyticus the primary sodium pump (which is inhibited by HOQNO) operates when the extracellular medium is alkaline, but under acidic conditions smf is generated by CCCP-sensitive (pmf-dependent) Na+ /H+ antiport; 1y(Na+ ) is maximum at ca. pH 8.5, minimum at ca. pH 6.0. In this organism smf can be used e.g. for the uptake of a range of amino acids and for rotation of the FLAGELLUM. [Na+ motive respiratory chain in marine bacteria: MS (1985) 2 65–71, and in Vibrio parahaemolyticus: JB (1985) 162 794–798.] Smf is also used to energize rotation of the polar flagellum in Vibrio cholerae [JB (1999) 181 1927–1930]; moreover, the exogenous and endogenous levels of sodium ions appear to be regulatory factors in the expression of virulence factors in V. cholerae [PNAS (1999) 96 3183–3187]. Propionigenium modestum apparently lacks a respiratory chain, but it can generate smf (see PROPIONIGENIUM); it seems that this organism can live independently of pmf – ATP being generated by a membrane-bound Na+ -ATPase [EMBO (1984) 3 1665–1670]. In the higher range of growth temperatures, the cytoplasmic membrane tends to become more permeable to both protons and sodium ions; however, the increase in permeability is greater for protons than it is for sodium ions. At these higher temperatures, organisms whose energy metabolism is based on protons have to use more energy to generate a given level of pmf – simply in order to compensate for the higher rate of inward diffusion of protons. In some organisms, the composition of the cytoplasmic membrane is such that this problem is minimized. However, some thermophilic bacteria do not use protons in their energy metabolism; for example, Clostridium fervidus uses sodium ions as the sole energy-coupling ion (i.e. pmf is not used in this species). [Ion permeability at high temperatures: FEMS Reviews (1996) 18 139–148.] [Enzymes that translocate sodium ions: BBA (1997) 1318 11–51.] sodium perborate See HYDROGEN PEROXIDE (a). sodium o-phenylphenate See PHENOLS. sodium polyanetholsulphonate See SPS. sodium pump See ION TRANSPORT. sodoku See RAT-BITE FEVER. soft chancre Syn. CHANCROID. soft core ham A canned ham (see CANNING) which has undergone spoilage (e.g. souring) due to the growth of e.g. Enterococcus faecalis var. liquefaciens. (See also FLAT SOUR.) soft rot (1) (of timber) A softening – initially superficial, becoming progressively deeper – in wood which is very moist, or which is kept wet and aerobic (e.g. the wooden slats in cooling towers); it is due to the growth of various cellulolytic ascomycetes (e.g. Chaetomium globosum) and deuteromycetes (e.g. Humicola, Monodictys) within the cell walls (S2 layer) of the wood. Soft rot fungi can cause serious economic losses of timber, but they do not become established if there is competition from other wood-rotting fungi (e.g. basidiomycetes). [Book ref. 39, pp. 165–169; ultrastructure of soft rot fungi: Mycol. 717

soft swell (1985) 77 447–463, 594–605.] (See also TIMBER SPOILAGE; TIM-

field; the resonating metal is mechanically linked to a metal probe (a cylindrical metal rod) which dips into the liquid and acts as the transmitter of sound energy. The sound waves used are often between 10 kHz and 25 kHz with amplitudes of ca. 10–50 µm. (1 kHz = 1 kc/s = 1000 cycles/second.) sonifier Syn. SONICATOR. sooty bark A disease of Acer spp (maple, sycamore) caused by Cryptostroma corticale; the bark of standing trees peels away to reveal dark-brown masses of conidia. (See also MAPLE BARK STRIPPERS’ DISEASE.) sooty moulds Fungi of the family Capnodiaceae and of certain other families of the order DOTHIDEALES. The organisms grow epiphytically, utilizing HONEYDEW, and form dark, spongy, hyphal mats on the surfaces of certain plants. Genera: e.g. Capnodium, Scorias. (cf. BLACK MILDEWS.) sop locus See PARTITION. SopA protein See PROTEIN SECRETION (type IV systems). SopB See FOOD POISONING (Salmonella). sophorolipids Extracellular glycolipid BIOSURFACTANTS produced by ‘Torulopsis’ sp during growth on hydrocarbons; they consist of sophorose covalently linked to the hydroxy group of a hydroxy fatty acid. sophorose b-D-Glucopyranosyl-(1 → 2)-D-glucopyranose – an effective inducer or certain CELLULASES. It occurs e.g. in certain plant glycosides and as an impurity in commercial glucose. soralium (lichenol.) A delimited mass of soredia (see SOREDIUM) present on the thallus in certain lichens. Soralia may occur in positions and forms which are characteristic for a given lichen species: they may be e.g. marginal (at the edges of the thallus), capitate (at the tips of lobes or branches), laminal (on the upper or lower surface of the thallus), etc. Sorangium See MYXOBACTERALES. sorbates See SORBIC ACID. sorbic acid (CH3 (CH=CH)2 COOH) An antibacterial and antifungal ORGANIC ACID used (as the free acid or e.g. as the potassium salt) as a PRESERVATIVE (e.g., in soft drinks, wines, pickles, cheese, pharmaceuticals). It has been reported that both dissociated and undissociated forms of sorbic acid have antimicrobial activity, but that organisms differ greatly in their susceptibilities [JAB (1983) 54 383–389]. Potassium sorbate (1–2% w/v) has been shown to reduce the germination rate of Clostridium botulinum type E endospores under acidic conditions [AEM (1982) 44 1212–1221]. sorbitol (glucitol) The POLYOL corresponding to glucose; Dsorbitol may be obtained e.g. by reduction of D-glucose, Dfructose or L-sorbose (see also ASCORBIC ACID). Sorbitol occurs naturally e.g. in certain plants, including a few unicellular green algae and a single red alga (Bostrychia scorpioides) [Book ref. 37, pp. 165–167]. D-Sorbitol is used e.g. as a food sweetener for diabetics, and as a substrate in biochemical characterization tests for bacteria (it is attacked by many species). sorbitol–MacConkey agar See EHEC. sorbose fermentation A commercial FERMENTATION (sense 2) in which D-sorbitol (see SORBITOL) is oxidized to the 2ketohexose L-sorbose by Acetobacter or Gluconobacter spp, especially G. oxydans (‘Acetobacter suboxydans’ ). L-Sorbose is used mainly as an intermediate in the manufacture of ASCORBIC ACID. Sordaria A genus of fungi (order SORDARIALES) which occur e.g. on dung and soil; the organisms form brown or black ascospores in persistent asci within dark perithecia – see ASCOSPORE for mode of spore discharge. Many species apparently do not form conidia. S. fimicola is homothallic.

BER PRESERVATION.)

(2) (of fruit and vegetables) A type of rot, caused by pectinolytic organisms, in which fruit or vegetables degenerate into a wet slimy mass. In acidic fruits (e.g. tomatoes, apples) soft rot is commonly caused by pectinolytic fungi (e.g. species of Botrytis, Penicillium, Rhizopus), while in non-acid fruits and vegetables (e.g. potatoes, carrots) it is more commonly caused by bacteria (e.g. species of Clostridium, Erwinia, Pseudomonas). (See also BROWN ROT (sense 2) and PECTIC ENZYMES; cf. DRY ROT (2).) soft swell See SWELL. sog gene See CONJUGATION (1b) (i). soil-borne wheat mosaic virus (SBWMV) A rod-shaped ssRNAcontaining virus which causes mosaic, stunting and yield reduction in winter wheat in parts of Europe, Japan and the USA. It is transmitted by the ‘fungus’ Polymyxa graminis. Isolates of SBWMV consist of at least two components, virion I (281–300 nm long) and virion II (138–160 or 92–110 nm long) – both of which are necessary for infectivity. SBWMV has been classified with the TOBAMOVIRUSES, but in view of its bipartite nature and mode of transmission it has been proposed as the type member of the furoviruses (fungus-borne rod-shaped viruses); other members of the group may include e.g. BEET NECROTIC YELLOW VEIN VIRUS, potato mop top virus, and peanut clump virus [JGV (1984) 65 119–127]. Solanum nodiflorum mottle virus (SNMV) See VELVET TOBACCO MOTTLE VIRUS and VIRUSOID. solfatara A dormant or decadent volcanic vent which (gently) emits sulphurous gases. solid-phase immunoelectron microscopy See SMALL ROUND STRUCTURED VIRUSES. Solorina A genus of foliose LICHENS (order PELTIGERALES). Photobiont: Coccomyxa, usually also with Nostoc. In e.g. S. spongiosa the thallus consists of two distinct parts: rounded, bright-green, Coccomyxa-containing lobes, each with a large, central, pitcher-shaped apopthecium, and blue-black, Nostoccontaining squamules. In S. crocea, Nostoc occurs within the thallus in a layer below the green algal layer. In S. saccata, Nostoc occurs in discrete internal cephalodia. Solorina spp occur mainly on calcareous soils, particularly at high altitudes. solvent fermentation Syn. ACETONE–BUTANOL FERMENTATION. somatic (1) Refers to an assimilatory, ‘vegetative’ (i.e., nonreproductive) structure or function. (2) Refers to the ‘body’ or main part of a cell. Thus, e.g. a somatic antigen is a molecule which forms part of the body of a cell, usually at the cell surface, rather than one which occurs e.g. in a capsule or flagellum. (See e.g. O ANTIGENS.) (3) Refers to ‘common pili’, i.e., FIMBRIAE, as opposed to PILI. somatic cell hybridization See HYBRIDOMA. somatic hypermutation See ANTIBODY FORMATION. somatogamy The fusion of somatic (vegetative) cells or hyphae involving PLASMOGAMY but not KARYOGAMY. Sonacide An acidic GLUTARALDEHYDE solution. Sonderia See TRICHOSTOMATIDA. sonicate (1) (verb) To carry out SONICATION. (2) (noun) The product of sonication. sonication The use of audible sound waves, produced by a SONICATOR, e.g. for the disintegration of cells in a liquid medium (cf. ULTRASONICATION). sonicator (sonifier) An instrument which provides sound energy for SONICATION or ULTRASONICATION. Sonicators commonly work on the principle of magnetostriction: the resonant deformation exhibited by certain types of metal in an alternating magnetic 718

SOS system Sordariales An order of fungi (subdivision ASCOMYCOTINA) which occur typically as saprotrophs on wood, soil or dung; the organisms typically form perithecia which are not immersed in a stroma and in which a hamathecium is absent. Asci: unitunicate, cylindrical to clavate, sometimes deliquescent. Ascospores: often dark, sometimes appendaged or bearing a gelatinous coat. Genera include e.g. Cercophora, CHAETOMIUM, Melanospora, NEUROSPORA, Nitschkea, PODOSPORA, SORDARIA, Sphaerodes, Triangularia. sordelliolysin See THIOL-ACTIVATED CYTOLYSINS. sorediate Bearing or consisting of soredia. soredium (lichenol.) A vegetative propagule (25–100 µm diam.) consisting of a few algal cells enmeshed in a few fungal hyphae; there is no cortex. Soredia appear, macroscopically, as powdery or granular structures on the thallus surface – often occurring in clusters (see SORALIUM). They originate in the medulla and are pushed up through pores or cracks in the cortex. Soret band See CYTOCHROMES. sori See SORUS. sorocarp A fruiting body, formed by certain SLIME MOULDS, consisting of a stalk bearing a mass of spores or chains of spores. (cf. SOROCYST.) sorocyst A fruiting body, formed by certain SLIME MOULDS, which resembles a SOROCARP but lacks a stalk. Sorodiscus See PLASMODIOPHOROMYCETES. sorogen In cellular slime moulds (e.g. DICTYOSTELIUM): the total cell mass which is undergoing differentiation to form a sorocarp. Sorosphaera See PLASMODIOPHOROMYCETES. sortase In Staphylococcus aureus: an enzyme, associated with the cytoplasmic membrane, which catalyses a reaction in which certain proteins, secreted through the membrane, undergo sitespecific cleavage and covalent linkage to the cell envelope peptidoglycan. Such proteins, which are thus tethered to the cell wall (cf. AUTODISPLAY in Escherichia coli ), are characterized by a C-terminal cell wall sorting signal that includes the conserved sequence LPXTG (see AMINO ACIDS); sortase cleaves between threonine and glycine and links the threonine residue to peptidoglycan. PROTEIN A is an example of a cell-wall-anchored protein. [Sortase-catalysed anchoring of surface proteins to the cell wall of S. aureus: Mol. Microbiol. (2001) 40 1049–1057.] sorus (pl. sori) A type of fruiting structure composed essentially of a mass of spores (e.g. in fungi of the Uredinales and Ustilaginales, and in certain SLIME MOULDS) or sporangia (e.g. in SYNCHYTRIUM). SOS box See SOS SYSTEM. SOS chromotest A colorimetric assay for GENOTOXINS using a genetically engineered strain of Escherichia coli. In this strain the SOS gene sulA (= sfiA) is fused with lacZ such that lacZ (structural gene for b-galactosidase) behaves as an SOS gene, being induced in response to DNA damage (see SOS SYSTEM). The strain also has mutations in uvrA (preventing excision repair) and in rfa (rendering it LPS-deficient and more permeable to certain chemicals); it also synthesizes alkaline phosphatase constitutively. Basically, the test involves incubating cultures of the ‘tester’ strain with various concentrations of a suspected pected genotoxin, and assaying for b-galactosidase activity using (e.g.) ONPG as substrate. The possibility that the chemical under test may inhibit protein synthesis can be excluded by assaying for alkaline phosphatase activity. [Mut. Res. (1985) 147 65–78, 79–95.] (cf. AMES TEST.) SOS mutagenesis See SOS SYSTEM. SOS response In Escherichia coli : expression of genes of the SOS SYSTEM in response to conditions which induce that system.

SOS system A system in which the expression of certain genes (‘SOS genes’) is induced (turned on, or enhanced) in response to damaged DNA or to inhibition of DNA replication – caused e.g. by the effects of ULTRAVIOLET RADIATION or the action of an ALKYLATING AGENT or quinolone antibiotic (such as NALIDIXIC ACID). (The SOS system can also be induced e.g. by the CcdB toxin: an agent, encoded by the F plasmid, which affects gyrase at sites other than those targeted by the quinolone antibiotics [TIM (1998) 6 269–275].) The SOS response results in e.g. inhibition of cell division, an increased capacity for DNA repair, alleviation of restriction, an altered pattern of energy metabolism, and (in those strains which contain a COLICIN PLASMID) production of colicin; it also gives rise to an increased rate of mutation. The SOS system has been studied mainly in Escherichia coli, and the following account refers primarily to the operation of the SOS system in that organism. Control of the SOS response. The SOS system consists of about 30 unlinked genes which are normally repressed by the LexA protein (lexA gene product). LexA (perhaps as a dimer) inhibits transcription by binding to an operator sequence (an SOS box ) in the promoter region of each gene or operon; the binding site for LexA is apparently the consensus sequence 5′ -CTGTN8 ACAG-3′ (in which N8 is an 8-nucleotide sequence). Different SOS boxes have different levels of affinity for LexA, and many of the SOS genes are expressed at low levels even in the repressed state. (At least one SOS gene, uvrB, has a second promoter which is not subject to control by LexA.) The LexA protein also represses its own synthesis; however, the SOS box of the lexA gene has a low affinity for LexA, so that there is always enough LexA to repress the other SOS genes. Damaged DNA ‘activates’ the RECA PROTEIN in an unknown way, i.e. the precise nature of the SOS-inducing signal is not known – although it is generally believed to involve a region of ssDNA and/or product(s) of DNA degradation. Activated RecA (designated RecA∗ ) behaves as a CO-PROTEASE which triggers the autocatalytic cleavage of LexA – permitting expression of the SOS genes. In vitro studies on the cleavage of LexA have suggested that cleavage occurs more rapidly when a chi (c) site (5′ -GCTGGTGG-3′ ) occurs near a double-stranded break in DNA; it may be that the presence of c promotes activation of RecA [Cell (1998) 95 975–979]. Weak SOS-inducing signals (due e.g. to low-level damage to DNA) may lower the intracellular concentration of LexA to only a limited extent – so that only those SOS genes with low-affinity SOS boxes will be induced. Inhibition of cell division. One aspect of the SOS response is a temporary inhibition of septum formation (and, hence, cell division); mutants in which the SOS system is constitutively de-repressed form aseptate filaments. During induction of the SOS system, septum formation is prevented as a result of inhibition of polymerization of the FtsZ protein (product of the ftsZ gene: see ‘Z ring’ in CELL CYCLE (b)). Polymerization of FtsZ is blocked by SulA, product of the SOS gene sulA (= sfiA) [JB (1998) 180 3946–3953]; cells may continue to grow as septum-less filaments. (Previously, some mutant alleles of ftsZ were referred to as sulB and sfiB.) SulA is normally very unstable, so that when repression of sulA is re-imposed normal septation is rapidly restored. At least part of the instability of SulA is due to its proteolytic inactivation by the product of the lon gene; in lon mutants SulA is much more stable, and induction of the SOS response – even by mild ultraviolet radiation – may lead to lethal filamentation. 719

souma (Lon is a HEAT-SHOCK PROTEIN; note that the heat-shock response can be triggered by certain factors – such as ultraviolet radiation – which induce the SOS system.) A temporary inhibition of cell division may be advantageous to the cell in that the cell is given time to carry out repairs to damaged DNA. DNA repair. The UvrABC-dependent nucleotide excision repair system (including genes uvrA and uvrB ) and the RECOMBINATION REPAIR system are enhanced in the SOS response; these repair systems have a high degree of accuracy (‘error-free’ repair). Another repair system, which is apparently expressed only when the SOS system is induced, involves genes umuC and umuD; the operation of this so-called ‘error-prone’ repair system (also called mutagenic repair) results in an increased rate of mutation (which is referred to as SOS mutagenesis). In this process, RecA∗ , acting as a co-protease, mediates autocatalytic cleavage of UmuD to an active fragment, UmuD′ (see DNA POLYMERASE V). SOS mutagenesis is believed to involve DNA (repair) synthesis on a template strand that contains a ‘lesion’ – e.g. a pyrimidine dimer (two adjacent, covalently linked pyrimidines on the same strand); such translesion synthesis is likely to involve specific DNA polymerase(s) induced as part of the SOS response – including DNA POLYMERASE V, DNA POLYMERASE IV and DNA polymerase II (polB gene product) [TIBS (2000) 25 74–79]. Because of a local loss of base-pairing specificity at the lesion, repair synthesis is likely to introduce incorrect bases and give rise to a mutant genome. (See also WEIGLE REACTIVATION.) Once the damaged DNA has been repaired, RecA becomes inactive as a co-protease; as the lexA gene is induced during the SOS response, the high level of LexA being synthesized means that, when activated RecA disappears, repression of the SOS genes (and restoration of normal cell function) can occur rapidly. Systems resembling the SOS system in E. coli have been observed in some other Gram-negative bacteria – e.g. species of Bacteroides, Rhizobium and Salmonella – as well as in Bacillus subtilis (‘SOB system’). Many bacteria appear to be inherently resistant to mutagenesis induced by ultraviolet radiation, and seem not to possess a umuDC function; such bacteria include Deinococcus radiodurans, Haemophilus influenzae, Proteus mirabilis, Streptococcus pneumoniae and Salmonella typhimurium. Functional homologues of umuC and umuD are carried by certain conjugative plasmids (e.g. ColI, R46 and its derivative pKM101, R205); the genes mucA and mucB in pKM101 are able to suppress the non-mutability of E. coli umuC and umuD mutants, and when introduced into cells which normally lack a umuCD system, pKM101 can decrease the susceptibility of those cells to killing while increasing their susceptibility to mutagenesis on exposure to umuCD-dependent mutagens. (See also AMES TEST.) [Plasmid genes affecting DNA repair and mutation: JCS (1987) 6 (supplement) 303–321.] The SOS system may be viewed as an adaptive genetic response to specific types of unfavourable environment. Under these conditions it is advantageous for bacteria to be able to make essential repairs and to adapt rapidly by making use of any (fortuitous) new combinations of nucleotides that may enhance their survival. This is reflected in increased repair activity and also in SOS mutagenesis – the latter offering the possibility of beneficial as well as lethal mutations. Suppression of restriction may favour exploitation of imported DNA, while inhibition of cell division may help e.g. to conserve energy and avoid the formation of non-viable daughter cells.

Error-prone repair in in vitro mutagenesis. A variety of mutagenic agents depend on the umuDC system for their mutagenic effects; thus, umuDC mutants of E. coli are resistant to the mutagenic effects of e.g. ultraviolet radiation and methylmethane sulphonate (see ALKYLATING AGENTS) – but can still be mutated by agents such as MNNG and ethylmethane sulphonate (see ALKYLATING AGENTS) which cause lesions leading directly to base mispairing. souma NAGANA caused (usually or exclusively) by Trypanosoma vivax. sour cream Cultured sour cream is made by the fermentation of pasteurized and homogenized cream (18–20% milk fat) using the same organisms as for BUTTERMILK. sourdough bread See BREAD-MAKING. South American blastomycosis Syn. PARACOCIDIOIDOMYCOSIS. Southampton virus See SMALL ROUND STRUCTURED VIRUSES. Southern bacterial wilt Syn. GRANVILLE WILT. southern bean mosaic virus See SOBEMOVIRUSES. Southern blot (Southern blotting) (1) A BLOTTING technique in which DNA is transferred from a gel to a nitrocellulose matrix (see figure). (2) Erroneously, a synonym of SOUTHERN HYBRIDIZATION. Southern hybridization A procedure used e.g. to detect a specific sequence of nucleotides among fragments of DNA which have been separated by gel electrophoresis. Initially, using the SOUTHERN BLOT technique (q.v.), single-stranded forms of the fragments are bound to a matrix. In the next step (Southern hybridization) the matrix is exposed to a labelled PROBE complementary to the sequence of interest; HYBRIDIZATION (sense 1) between the probe and a specific region of the blotted DNA (detected by the probe’s label) indicates the required sequence. Southwestern blotting A technique for detecting DNA-binding proteins in a cell lysate etc. The sample is initially subjected to gel electrophoresis, and the proteins thus separated are electroblotted (see BLOTTING) onto a nitrocellulose filter. The affinity of any blotted protein for a specific DNA sequence is then determined by using labelled DNA sequences as probes and detecting the label of any probe which has bound to a given protein. soy paste Syn. MISO. soy sauce (shoyu) A condiment traditionally prepared by fermenting soybeans and (usually) wheat (cf. TAMARI SAUCE). A KOJI (made from whole or defatted soybeans and crushed roasted wheat) is transferred to a deep vessel and is suspended in brine (to 17–19% NaCl) to form ‘moromi’; the moromi is allowed to ferment, usually with occasional agitation and aeration, for e.g. 6–8 months or more. During this stage, enzymes from the koji mould hydrolyse proteins and starch in the raw materials to provide low-MWt substrates which are initially fermented primarily by lactic acid bacteria (e.g. Lactobacillus delbrueckii, Pediococcus halophilus); the pH falls rapidly to ca. 5.0 or lower, after which fermentation is continued primarily by yeasts (e.g. Zygosaccharomyces rouxii ). ‘Torulopsis’ spp (Candida etchellsii, C. versatilis) may grow at later stages in the fermentation; these yeasts produce substances which contribute to the flavour and aroma of the final product. The soy sauce fermentation may be carried out by microorganisms naturally present in the raw materials, or pure cultures of selected strains may be used. After the fermentation, the raw soy sauce is decanted or pressed from the solid residue and is pasteurized, filtered and bottled. [Book ref. 5, pp. 39–86; microbes used in soy sauce manufacture: Food Mic. (1984) 1 339–347.] 720

species weight nitrocellulose

paper towels gel

wick

SOUTHERN BLOT (Southern blotting): the transfer of DNA fragments from a gel strip to a sheet of nitrocellulose by capillary action. Within the gel, the fragments are distributed in discrete zones, according to size, having been previously separated by gel electrophoresis. The fragments are first denatured (made single-stranded) by exposing the gel to alkali; the gel is then exposed to neutral buffer and arranged as shown in the diagram. Driven by capillary action, the neutral, saline solution in the dish rises, via the wick, into and through the gel, through the (permeable) nitrocellulose, and into the stack of paper towels; this upward stream of liquid carries the DNA fragments from the gel to the sheet of nitrocellulose. Importantly, the relative positions of fragments on the sheet are the same as they were in the gel. The sheet is removed and baked at 70° C under vacuum to bind the DNA. The fragments can then be examined e.g. by exposing the sheet to a specific labelled probe; probe–target binding (= Southern hybridization), detected by the probe’s label, identifies the required sequence. One alternative to nitrocellulose is APT PAPER (q.v.). This not only avoids the need for baking, it also permits removal of probes – so that different probes can be subsequently used on the same sheet. Northern blotting refers to the transfer of RNA from gel to matrix. Western blotting refers to the transfer of protein from gel to matrix. Electroblotting is a faster method which uses an electric field for effecting transfer. Figure reproduced from Bacteria 5th edition, Figure 8.13, page 195, Paul Singleton (1999) copyright John Wiley & Sons Ltd, UK (ISBN 0471-98880-4) with permission from the publisher.

soybean casein digest agar Syn. TRYPTICASE–SOY AGAR. soybean dwarf virus See LUTEOVIRUSES. soybean mosaic virus See POTYVIRUSES. Sp Pattern coefficient. In the comparison of two strains by NUMERICAL TAXONOMY: a coefficient which indicates the degree of similarity corrected for any difference(s) due solely to interstrain differences in metabolic vigour. (cf. entry Dp .) sp An unspecified SPECIES: e.g. Bacillus sp (a species of Bacillus); spp indicates two or more unspecified species or may indicate all the species of the given genus. sp. n. See SPECIES NOVA. sp. nov. See SPECIES NOVA. SpA PROTEIN A. Sparassidaceae See APHYLLOPHORALES. Sparassis A genus of fungi (family Sparassidaceae). S. crispa (the ‘brain fungus’ or ‘cauliflower fungus’) is an edible species which typically grows at the base of conifer trees; the thallus (branching, flattened lobes) is pale buff, up to ca. 50 cm across, and the basidiospores are whitish or cream-coloured, ca. 6 × 4 µm. sparfloxacin See QUINOLONE ANTIBIOTICS. sparrowpox virus See AVIPOXVIRUS. sparsomycin An ANTIBIOTIC which inhibits PROTEIN SYNTHESIS in both prokaryotic and eukaryotic cells; it binds to the larger ribosomal subunit and inhibits the peptidyl transferase reaction. Spartina mottle virus See POTYVIRUSES. spasmoneme The MYONEME within the stalk of a contractile peritrich (such as VORTICELLA). Spathularia See HELOTIALES. Spathulospora See SPATHULOSPORALES. Spathulosporales An order of fungi (subdivision ASCOMYCOTINA) which are parasitic on red algae. The thallus is a crustose

or intracellular stroma. Ascocarp: perithecioid. Asci: unitunicate, deliquescent. Ascospores: appendaged, some spoon-shaped (spathulate). The sole genus, Spathulospora, is classified in the LABOULBENIALES by some authors. spawn (mycol.) Mycelium – usually of Agaricus brunnescens (A. bisporus) – growing e.g. in a block (‘brick’) of horse manure, used as an inoculum in MUSHROOM CULTIVATION. It may be derived from a previous culture or may be grown by inoculating sterile compost with spores of a selected strain. spc operon In e.g. Escherichia coli: an OPERON containing genes for r-proteins L14, L24, L5, S14, S8, L6, L18, S5, L30, and L15, and gene prlA (= secY: involved in protein secretion), listed in order of transcription. (See RIBOSOME.) SpeI See RESTRICTION ENDONUCLEASE (table). speB gene (Streptococcus) See NECROTIZING FASCIITIS. special form Syn. FORMA SPECIALIS. specialized transduction See TRANSDUCTION. speciation (1) The evolutionary process which leads to the formation of new species. (2) The taxonomic process by which species are delimited. species (microbiol.) (singular and plural: species) One of the less-inclusive categories in TAXONOMY – the individuals of a given species displaying a high degree of mutual similarity; a universally applicable and acceptable definition of ‘species’ is currently not available. Among microorganisms, SPECIATION (sense 2) was particularly unsatisfactory for prokaryotes prior to the mid-1960s. Since then, molecular methods have progressively provided a basis for what is thought to be a PHYLOGENETIC CLASSIFICATION of these organisms. Such methods include DNA HOMOLOGY studies and the comparison of organisms on the basis of nucleotide sequences in their 16S rRNA. 721

species nova spermatiophore A modified or undifferentiated hypha which bears a SPERMATIUM. spermatium A non-motile male reproductive cell which can function in SPERMATIZATION. (cf. MICROCONIDIUM (sense 1) and PYCNIOSPORE.) spermatization In certain higher fungi: the union of a SPERMATIUM with a female reproductive structure (e.g. a TRICHOGYNE or a FLEXUOUS HYPHA). spermatogonium Syn. SPERMAGONIUM. spermidine See POLYAMINES. spermine See POLYAMINES. spermogonium Syn. SPERMAGONIUM. Spermophthora See METSCHNIKOWIACEAE. Spermophthoraceae Syn. METSCHNIKOWIACEAE. SPF SPECIFIC PATHOGEN FREE. SPf66 vaccine See MALARIA. Sphacelaria See PHAEOPHYTA. Sphacelia A genus of fungi of the HYPHOMYCETES; teleomorphs occur e.g. in the genus CLAVICEPS. Sphaceloma A genus of fungi of the COELOMYCETES. Teleomorph: Elsino¨e. Sphacelotheca See USTILAGINALES. Sphaeractinomyxon See ACTINOSPOREA. Sphaeriales An order of fungi (subdivision ASCOMYCOTINA) which typically form carbonaceous perithecia (often containing filiform paraphyses) immersed in a stroma. Asci: unitunicate, cylindrical or ellipsoidal. Ascospores: aseptate or septate, colourless or dark. Genera: e.g. Ascotricha, Camarops, DALDINIA, Hypoxylon, XYLARIA. Sphaerobolus A genus of lignicolous and coprophilous fungi (order SCLERODERMATALES) formerly classified in the Nidulariales. S. stellatus forms globose basidiocarps (ca. 1.5–2.5 mm diam.) in which the peridium is composed of six layers. At maturity, the glebal mass is violently discharged following rupture of the peridium and the sudden eversion of certain inner layers; eversion occurs apparently as a result of increased osmotic pressure in one of the inner layers (due to the breakdown of glycogen to soluble sugars) and the consequent stress upon this (and an adjacent) layer on absorption of water. [Culturing for fruiting bodies: Mycol. (1984) 76 944–946.] sphaerocyst A spherical or ovoid cell, numbers of which occur in the TRAMA, and in other parts of the CONTEXT, e.g. in fungi of the genera Lactarius and Russula. sphaerocyte An (abnormal) spherical or subspherical form of an erythrocyte formed, e.g., as a result of the activity of Escherichia coli a-haemolysin. Sphaerocytophaga A genus of bacteria; the organisms are similar or identical to species of CAPNOCYTOPHAGA [Book ref. 45, pp. 356–379 (365)]. Sphaerodes See SORDARIALES. Sphaerodothis See POLYSTIGMATALES. sphaeromastigote A form assumed by the cells of species of Trypanosoma during certain stages of their life cycles: see TRYPANOSOMATIDAE. Sphaeromonas A genus of fungi found in the RUMEN. Sphaeromyxa See MYXOSPOREA. Sphaerophoraceae See CALICIALES. Sphaerophorus (1) (mycol.) See CALICIALES. (2) (bacteriol.) Obsolete genus of bacteria which are currently included in the genera BACTEROIDES and FUSOBACTERIUM. Sphaerophrya See SUCTORIA. sphaeroplast (spheroplast) A spherical or near-spherical, osmotically sensitive structure which resembles a PROTOPLAST but is

DNA homology studies suggest e.g. that bacterial strains whose DNA exhibits >70% relatedness are likely to belong to the same species. Moreover, 16S rRNA sequences in different species of a given genus have generally been found to differ by at least 1.5%. These two measurements therefore help to determine which strains belong to a given species and which strains belong to different species. However, certain species of Bacillus – which are clearly differentiated at the species level by DNA homology studies – were shown to have virtually identical sequences in their 16S rRNA molecules [IJSB (1992) 42 166–170]; a possible explanation is that the genomes of these species have diverged recently (on an evolutionary scale) and that their 16S rRNA sequences have had insufficient time to reflect the change. Strains within a given species may exhibit variation in character due e.g. to the effects of MUTATION (see also ECOTYPE; cf. ECAD) or to the acquisition (or loss) of a PLASMID. Strains can be differentiated by various TYPING techniques. The term ‘species’ is also used, for convenience, to refer to the organisms belonging to one or more given species – as, for example, in: ‘Gram-negative species were isolated from the sample’. (See also BINOMIAL, TYPE SPECIES; TYPE STRAIN.) species nova (n. sp.; sp. n.; sp. nov.) A designation used to indicate a newly proposed species at the time of its initial publication. specific epithet See BINOMIAL. specific growth rate (µ) Of a given organism: the number of grams of biomass formed per gram of biomass per hour; the unit of µ is hour−1 . In any given case, µ depends on factors which include the strain of organism, the temperature, and the concentration of nutrients. Under steady-state conditions in CONTINUOUS CULTURE µ can often be calculated from the Monod equation: s µ = µmax ks + s in which s is the concentration of a potentially limiting nutrient, µmax is the value of µ when the given nutrient is not limiting, and ks is numerically equal to the concentration of the given nutrient when µ = 0.5 µmax . (See also DILUTION RATE.) specific immunity Any form of IMMUNITY specific to a given antigen – including e.g. antibody-mediated protective immunity, hypersensitivity, immunological tolerance. (cf. NON-SPECIFIC IMMUNITY.) specific pathogen free (SPF) Refers to the condition of an animal which was born (or removed from the uterus) and reared under conditions in which specific pathogen(s) have been rigorously excluded. (cf. GNOTOBIOTIC.) specific-phase antigen See PHASE VARIATION. spectinomycin An aminocyclitol usually classified as an AMINOGLYCOSIDE ANTIBIOTIC (even though it does not contain an aminosugar). Spectinomycin is produced by Streptomyces spectabilis and is (reversibly) bacteriostatic. Spectinomycindependent strains of Escherichia coli have been found to be double mutants – one mutation conferring resistance to the drug by modifying ribosomal protein S5, the other conferring drug dependence [MGG (1977) 151 261–267]; spectinomycin does not support the growth of STREPTOMYCIN-dependent bacteria. spermagonium (syn. spermogonium, spermatogonium) In certain fungi: a structure within which male reproductive cells (spermatia) are formed. In rust fungi, a spermagonium is called a pycnium. 722

Spirillospora group at C-2 of sphingosine forms an amide bond with a longchain fatty acid (forming ceramide), and the terminal (C-1) hydroxyl is esterified with phosphorylcholine. sphingomyelinase A PHOSPHOLIPASE (q.v.) which cleaves SPHINGOMYELIN. An example is the staphylococcal b-HAEMOLYSIN, a C-type phospholipase which cleaves sphingomyelin to phosphorylcholine and ceramide. (See also HOT–COLD LYSIS.) Corynebacterium pseudotuberculosis (formerly C. ovis) forms a sphingomyelinase (a D-type phospholipase) which cleaves choline from sphingomyelin. sphingosine See SPHINGOLIPID. SPI Salmonella PATHOGENICITY ISLAND. spiculum A narrow, apical extension of a STERIGMA on which a spore is borne. spin killing A type of killing of sensitive strains of Paramecium by certain types of killer paramecia (e.g. strains containing Caedibacter varicaedens); affected cells swim with rapidly reversing rotational movements. spin label See ELECTRON SPIN RESONANCE. spina (pl. spinae) In certain prokaryotes (e.g. some pseudomonads): a hollow, rigid, apparently non-prosthecate appendage, one or more of which project from the cell surface; it is a thin-walled structure formed from a cross-linked helical filament. [Conical spinae: CJM (1984) 30 716–718. Possible function: JGM (1991) 137 1081–1086.] spinach latent virus See ILARVIRUSES. spindle (1) See MITOSIS and MEIOSIS. (2) (virol.) See ENTOMOPOXVIRINAE. spindle pole body (syn. centriolar plaque; polar plaque) In some types of eukaryotic cell (including e.g. Saccharomyces cerevisiae): a body which is embedded in the nuclear membrane and which can act e.g. as a MICROTUBULE-ORGANIZING CENTRE during MITOSIS. spinning disease A FISH DISEASE which affects the Atlantic menhaden (Brevoortia tyrannus); the disease tends to occur in large-scale annual epizootics with massive mortalities. Terminal symptoms include loss of coordination and erratic swimming behaviour. The causal agent is a virus which closely resembles (and may be identical to) IPN VIRUS. spinoculation Centrifugally-assisted enhancement of transduction efficiency (a procedure in which the virus vector and cells are centrifuged together). spira Refers to helical aerial hyphae – one of three categories used in a system for the morphological classification of streptomycetes; the other two categories are rectus–flexibilis (straight to flexuous hyphae) and retinaculum apertum (hook-shaped, looped, or spiral hyphae with one or two turns). [Disadvantages of the system: Book ref. 46, p. 2067.] spiral plate count method A method used for counting bacteria in samples of milk. Essentially, the inoculum is delivered from a syringe onto a rotating plate so that it is deposited along a spiral path; the volume of inoculum delivered to a particular region of the plate can be read off from the apparatus. A colony count is made after incubation of the plate. spiramycins See MACROLIDE ANTIBIOTICS. Spirillaceae A family of bacteria which formerly included the genera Campylobacter and Spirillum but which has been abandoned pending further taxonomic studies [Book ref. 22, p. 71]. Spirillospora A genus of bacteria (order ACTINOMYCETALES, wall type III; group: maduromycetes) which occur e.g. in soil and leaf litter. The organisms form thin (0.02%, and by phosphate >0.01 M. Carbohydrates are not utilized; carbon sources: salts of organic acids (e.g. succinate). GC%: 38. Type species: S. volutans, found in stagnant freshwater habitats. (cf. AQUASPIRILLUM; AZOSPIRILLUM; OCEANOSPIRILLUM; SPOROSPIRILLUM.) Species incertae sedis: ‘S. minus’ (= ‘S. minor ’), causal agent of one form of RAT-BITE FEVER; cells: ca. 0.2 × 3–5 µm, usually spiral, actively motile by one or more flagella at each pole. ‘S. pulli’, apparent causal agent of DIPHTHEROID STOMATITIS in chickens; cells: rigid spirals, ca. 1.0 × 5–12 µm, motile with one flagellum at each pole. [Book ref. 22, pp. 90–93. Culture, media etc: Book ref. 45, pp. 597–599.] spirits Alcoholic beverages prepared by the distillation of fermented liquors or mashes. The characteristic flavours and qualities of the various spirits are determined by the nature of the fermented raw materials, conditions of distillation, effects of ageing, etc. The fermentation stage generally resembles that in BREWING or WINE-MAKING. Use is made of yeast (Saccharomyces) strains which effect maximum attenuation (i.e. they convert the maximum amount of carbohydrate to alcohol); these strains are characterized by high alcohol-tolerance. Distillers’ yeasts produce a range of higher alcohols (FUSEL OIL) which contribute to the aroma and flavour of the product. Spirits are not subject to microbial spoilage owing to their high alcohol content. Bourbon is an American whisky (whiskey) made by distilling a fermented mash containing maize and rye. Brandy (cognac) is prepared by distilling grape wine. Gin is made by distilling fermented rye or maize worts and redistilling the product in a still containing herbs and juniper berries (‘botanicals’). Rum is a distillate of fermented molasses or sugarcane products. Tequila: see PULQUE. Whisky is distilled either from a wort derived from malted barley (malt whisky) or from a mash of unmalted grain (often barley or maize) mixed with a proportion of malted barley (grain whisky). Spirochaeta A genus of Gram-negative bacteria of the family SPIROCHAETACEAE; the organisms, which include both obligately and facultatively anaerobic species, occur as free-living inhabitants of freshwater and marine environments, including muds, and are common in H2 S-containing habitats. The cells are 0.2–0.75 × 5–250 µm; the type species, S. plicatilis, contains many periplasmic flagella per cell, but the other species contain only two per cell. The organisms are motile in liquids and can also creep over solid surfaces and migrate through agar (≤1%) – the latter feature being useful in isolation procedures. In most species the anaerobic metabolism of carbohydrates yields ethanol, acetate, CO2 and H2 ; S. zuelzerae forms lactate and succinate. GC%: ca. 51–65. Species differentiation is based on e.g. cell diameter, ability to grow aerobically, NaCl requirement and pigmentation. Six species are recognized [Book ref. 22, pp. 39–46]: S. aurantia

and S. halophila (both facultative anaerobes; S. halophila is halophilic and forms a red pigment); S. litoralis and S. stenostrepta (both obligate anaerobes; S. litoralis is halophilic); S. plicatilis (cell diameter ca. 0.75 µm); and S. zuelzerae (obligate anaerobe, forms succinate). (All species except S. plicatilis have been grown in pure culture.) Spirochaetaceae A family of anaerobic, facultatively anaerobic or microaerophilic bacteria of the order SPIROCHAETALES; the cells typically do not have hooked ends, their cell wall PEPTIDOGLYCAN contains the diamino acid L-ornithine, and their carbon and energy sources are carbohydrates and/or amino acids (cf. LEPTOSPIRACEAE). Genera: BORRELIA, CRISTISPIRA, SPIROCHAETA, TREPONEMA. Spirochaetales An order of helical, flexible, asporogenous, Gram type-negative bacteria which include free-living, parasitic and pathogenic species. The cells are 0.1–3.0 µm in width and 5–250 µm in length, according to species, and they divide by transverse binary fission; motility in liquid media involves periplasmic flagella (see below and FLAGELLAR MOTILITY), and the organisms can also creep over solid surfaces. Depending on size, spirochaetes may be seen by bright-field MICROSCOPY (e.g. after staining with dyes or silver-deposition techniques), by dark-field microscopy, or by fluorescence microscopy following treatment with fluorochrome-labelled antibodies. Species include anaerobes (obligate and facultative) and microaerophiles (family SPIROCHAETACEAE) and aerobes (family LEPTOSPIRACEAE). The organisms are chemoorganotrophs which have fermentative and/or respiratory (oxidative) type(s) of metabolism. Ultrastructure. The spirochaetal cell consists of a helical protoplasmic cylinder (= PROTOPLAST (sense 2) covered by a ‘cell wall’ of PEPTIDOGLYCAN), the whole being enclosed within an outer sheath (= outer envelope) similar to the OUTER MEMBRANE of other Gram type-negative bacteria; one or more periplasmic flagella (= axial fibrils, axial filaments, endoflagella, periplasmic fibrils) arise at each end of the protoplasmic cylinder and wind around the protoplasmic cylinder – i.e. they are located between the protoplasmic cylinder and the outer sheath. The periplasmic flagellum is similar in ultrastructure to the prokaryotic FLAGELLUM; the number of periplasmic flagella per cell is a stable characteristic of the various species and genera of spirochaetes. [Structure/motility of spirochaetes: JB (1996) 178 6539–6545.] Habitats. Spirochaetes occur in host tissues (BORRELIA, CRISTISPIRA, LEPTOSPIRA, TREPONEMA) and in soil and aquatic habitats (LEPTOSPIRA, SPIROCHAETA). Spirochaetes occur also in the hindgut of termites (see TERMITE–MICROBE ASSOCIATIONS); these have not been isolated in pure culture, and the names proposed for these organisms (e.g. Diplocalyx, Hollandina, Pillotina) have not been validly published [Book ref. 22, pp. 67–70]. spirochaete (spirochete) A member of the SPIROCHAETALES. Spirochona See HYPOSTOMATIA. Spirocystis A genus of protozoa (suborder EIMERIORINA) parasitic in oligochaetes. Spirogyra A genus of unbranched filamentous green algae (division CHLOROPHYTA) in which sexual reproduction occurs by a process of conjugation; flagellated cells are never formed. Species are common in standing fresh water; the filaments are usually free-floating, but are sometimes attached to stones etc. Each filament is composed of a chain of cylindrical cells (arranged end-to-end); the filaments are coated with mucilage and may be capable of GLIDING MOTILITY. Each cell has a thin peripheral layer of cytoplasm surrounding a large central vacuole; a single nucleus is suspended in the centre of the 724

split gene vacuole by fine cytoplasmic threads. The cytoplasm contains one or more (according to species) ribbon-like, spirally arranged chloroplasts (containing many pyrenoids) extending throughout the length of the cell. Asexual reproduction occurs by fragmentation of the filaments; zoospores are not formed. Sexual reproduction occurs by conjugation: typically, two filaments lie side-by-side (held together by mucilage), and a conjugation tube is formed between two juxtaposed cells (one cell in each filament: scalariform conjugation). (Conjugation can also occur between adjacent cells in a single filament: lateral conjugation.) One protoplast (designated male) passes from one cell to the other via the conjugation tube, and syngamy occurs. (In some species a zygote is formed within the conjugation tube.) The zygote develops a thick, resistant wall and undergoes a period of dormancy. Meiosis occurs before germination, and 3 of the 4 resulting nuclei disintegrate; on germination, a single haploid filament develops. Genera related to Spirogyra include e.g. MOUGEOTIA, ZYGNEMA and ZYGOGONIUM; see also DESMIDS. Spiromyces See KICKXELLALES. Spiroplasma A genus of facultatively anaerobic bacteria (family SPIROPLASMATACEAE) which occur as epiphytes or as intracellular or extracellular parasites or pathogens in a range of invertebrates and plants (see e.g. YELLOWS). (See also MLO and SRO.) Cells: pleomorphic, ranging from helical filaments (commonly 0.1–0.2 µm × 3.0–5.0 µm) which typically occur in the logarithmic phase of growth (and which may persist into the stationary phase), to branched non-helical filaments and to coccal and coccoid forms (ca. 0.3 µm diam.); in some infected tissues the cells of some strains may be indistinguishable from MLOs. Helical filaments contain a system of fibrils [JGM (1985) 131 983–992] which may be involved in the characteristic flexing and other movements of which these forms are capable; the cells lack flagella. NADH oxidase occurs in the cytoplasm (cf. ACHOLEPLASMA). The organisms are chemoorganotrophs which require sterols for growth; with the exception of SROs, they can be cultured e.g. on serum-containing media. GC%: ca. 25–31. Type species: S. citri. S. apis. The causal agent of a May-disease-like disorder of the honey bee (Apis mellifera) in France; isolated also e.g. from flowers. S. citri. Isolated e.g. from citrus plants suffering from STUBBORN DISEASE, from other naturally-infected plants (e.g. broad beans; see also CORN STUNT DISEASE), and from leafhoppers; some strains are pathogenic for honey-bees. S. floricola. Isolated e.g. from magnolia flowers; can cause disease in beetles of the genus Melolontha. S. kunkelii. See CORN STUNT DISEASE. S. mirum. Isolated e.g. from rabbit ticks; can cause disease in e.g. rodents and chick embryos under experimental conditions. Spiroplasma spp are divided into serogroups I (e.g. S. citri, S. melliferum), II (SROS), III (S. floricola), IV (S. apis) and V (S. mirum). (See also SPIROPLASMAVIRUSES.) Mycoplasma-like organisms have been referred to by the trivial name ‘phytoplasma’ [see ARM (2000) 54 221–255]. Spiroplasmataceae A family of (typically) helical and filamentous, cell-wall-free bacteria (order MYCOPLASMATALES) which are associated with various invertebrates and plants. Sole genus: SPIROPLASMA. [Book ref. 22, pp. 781–787.] spiroplasmaviruses BACTERIOPHAGES which infect Spiroplasma spp. SV-C1 phages are filamentous (230–280 × 10–15 nm) and

contain DNA; they may belong in the INOVIRIDAE. In SV-C2 phages there is an icosahedral-type head (52–58 × 48–51 nm) with a tail (75–83 × 6–8 nm) attached at one vertex. SVC3 phages (= C3 strain C3 phages) probably belong to the PODOVIRIDAE; the icosahedral-type head (ca. 40 × 35–37 nm) contains linear dsDNA (MWt 1.4 × 107 ) and has a short tail (13–18 × 6–8 nm) attached at one vertex. SV-C3 progeny virions seem to be released in host-derived membrane vesicles. (See also MYCOPLASMAVIRUSES). Spirosoma A genus of yellow-pigmented bacteria (family SPIROSOMACEAE). The cells, 0.5–1.0 × 1.5–6.0 µm, are commonly helical or curved rods – ‘ring-shaped’ forms sometimes being seen as a result of overlap of the ends of highly curved cells. Acid is formed from many carbohydrates. GC%: 51–53. Type species: S. linguale. Spirosomaceae A family of Gram-negative, obligately aerobic, chemoorganotrophic, pink- or yellow-pigmented bacteria which occur in soil and aquatic habitats; the organisms are rigid, straight, curved or spiral, non-motile rods. Growth (optimum temperature range: 20–30° C) occurs e.g. on peptone–yeast extract–glucose agar. Genera: FLECTOBACILLUS, RUNELLA, SPIROSOMA. [Book ref. 22, pp. 125–132.] Spirostomum A genus of ciliate protozoa (order HETEROTRICHIDA) which occur e.g. in microaerobic freshwater and estuarine habitats. Cells: elongate, cylindrical, up to ca. 4 mm in length – but able to contract to a fraction of their normal length; somatic ciliature is uniform, and the cytostome is lateral. A large posterior contractile vacuole discharges via a long canal which opens to the exterior near the anterior end. In some species (e.g. S. ambiguum) the macronucleus is moniliform, in others (e.g. S. teres) it is ovoid. spirotrich A member of the Spirotrichia. Spirotrichia See POLYHYMENOPHOREA. Spirotrichonympha See HYPERMASTIGIDA. Spirulina A genus of filamentous CYANOBACTERIA (section III) in which the trichomes are helical with little or no constriction between adjacent cells. GC%: 44–53. The trichomes show GLIDING MOTILITY, and the tips are capable of a twitching or jerking motion which may be brought about by a contractile (actin-like?) protein [Book ref. 76, pp. 420–421]. Spirulina typically occurs in warm, saline, alkaline lakes, where it forms dense tangled masses. For centuries it has been used as food by people in the Lake Chad region of Africa, and was also eaten by the Aztecs of ancient Mexico; in Africa, the masses of growth are collected, sun-dried, and made into thin cakes which may be eaten directly or after cooking. Spitzenk¨orper (apical granule) A small, densely staining body which occurs, close to the cytoplasmic membrane, in the tip of an actively growing fungal hypha; in at least some fungi it consists of a cluster of vesicles associated with microfilaments. (See also GROWTH (fungal).) spleen focus-forming virus (SFFV) See FRIEND VIRUS and RAUSCHER VIRUS. splenic fever See ANTHRAX. splice sites See SPLIT GENE. spliceosome See SPLIT GENE (a). splicing (1) (of RNA) See SPLIT GENE. (2) (of DNA) See e.g. CLONING. split gene (interrupted gene) A structural gene (encoding e.g. a protein, rRNA or tRNA) that contains one, several or many specific sequences of nucleotides (intervening sequences; introns) which, although represented in the primary RNA transcript of the gene, are absent from the mature RNA molecule (mRNA, 725

split gene initially involves cleavage at the 5′ splice site, thus releasing the 3′ end of the 5′ exon, and formation of an intron–3′ -exon intermediate in the form of a lariat (a tailed, circular molecule); the lariat results from the formation of a 2′ –5′ phosphodiester bond between the (free) 5′ end of the intron and a site within the intron near its 3′ end (the branch point). In yeast, this branch occurs at the last adenine residue in the TACTAAC box. Subsequently, the 3′ splice site is cleaved, and the 5′ and 3′ exons are ligated. The intron, released as a lariat, is ‘debranched’, enzymically, to release a free linear intron (which is degraded in vivo). Debranching enzymes from S. cerevisiae and Schizosaccharomyces pombe exhibit some homology with the human RNA lariat debranching enzyme [NAR (2000) 28 3666–3673]. Secondary or tertiary structure in the intron appears not to be important for the juxtaposition of splicing sites in nuclear introns (cf. other mechanisms below). The splicing reaction depends on certain small molecules of RNA – snRNAs (see SNRNA) – which apparently act as external guide sequences (EGSs) to locate the relevant sites in the premRNA. In higher eukaryotes, U1 snRNP binds to the 5′ splice site (the 5′ end of U1 snRNA probably base-pairing with the conserved sequence GUNAGU), U2 snRNP binds to the branch point, and U5 snRNP probably binds to the 3′ splice site. Interactions between the snRNPs, and between snRNPs and the RNA substrate, presumably bring about juxtaposition of the 3′ and 5′ splice sites. Splicing of the pre-mRNAs in yeasts and in higher eukaryotes involves a large (40S–60S) ribonucleoprotein particle (the spliceosome) which, in e.g. human cells, contains U snRNPs; in yeasts, the spliceosome contains at least three snRNAs, and its assembly is dependent on the presence of a 5′ splice site and a TACTAAC box within the RNA [Cell (1986) 45 869–877]. (b) Group I introns (= class I introns). Introns of this type occur in nuclear pre-rRNA of Tetrahymena thermophila and Physarum polycephalum, in several fungal mitochondrial prerRNAs and pre-mRNAs, and in certain chloroplast tRNA genes. They are characterized by a common splicing mechanism and by a number of conserved sequences; interaction between these sequences apparently folds the intron into a ‘core structure’ in which the 5′ and 3′ splice sites are brought into close proximity. Excision of this type of intron is an intrinsic property of the RNA itself, i.e. group I introns are self-splicing or autocatalytic; in some cases splicing can occur in vitro when the RNA is incubated with divalent cations and guanosine or a guanosine nucleotide (GMP, GDP or GTP – or a G at the 3′ end of an oligo- or polynucleotide) in the absence of protein. (cf. RIBOZYME.) Splicing involves two distinct and independent cleavage–ligation steps – and transesterification reactions in which the total number of phosphodiester bonds remains constant (so that splicing does not require an additional source of energy). Cleavage occurs first at the 5′ splice site concomitantly with the formation of a phosphodiester bond between the 3′ -OH of a guanine nucleoside or nucleotide and the 5′ end of the intron. Subsequently, cleavage of the 3′ splice site is coupled with ligation of the 5′ and 3′ exons. In many cases the excised linear intron circularizes by a transesterification reaction in which the 3′ -terminal residue (usually or always a guanosine residue) forms a covalent bond at a site near the 5′ end, the terminal oligonucleotide being released. It has been proposed that, during the splicing process, a nucleotide sequence within the 5′ exon (adjacent to the 5′ splice site) base-pairs with a complementary sequence within the intron

tRNA etc.) and, hence, do not encode any part of the gene product. Thus, maturation of the primary RNA transcript of a split gene must involve a process of splicing in which sequence(s) corresponding to intron(s) are deleted (‘spliced out’) and the remaining sequences (termed exons) are joined together; for example, in the case of mRNA (q.v.), the amalgamated exons form the complete coding sequence of the gene together with any non-coding leader and/or trailer sequences. In some cases a given gene can be spliced in different ways to yield different versions of the encoded product, i.e. splicing can give rise to different combinations of exons – producing correspondingly different coding sequences. Such alternative splicing can be advantageous to a cell e.g. in that synthesis of multiple products from a single gene permits economy in the size of the genome. Introns are often non-coding sequences that are degraded following excision – but see (b) and (c), below, and INTRON HOMING. Split genes occur in eukaryotes and in certain prokaryotes (including bacteria and archaeans) and viruses. Many (or most) eukaryotic genes contain at least one intron – sometimes many; the gene encoding type I collagen appears to contain about 50 introns. By contrast, the (human) insulin gene contains only one intron, while the gene encoding interferon-b is intron-less. In higher eukaryotes, many (perhaps most) of the nuclear structural genes are split genes, but in typical eukaryotic microorganisms (e.g. Dictyostelium, Saccharomyces) fewer of these genes are reported to contain introns, and the introns tend to be smaller than those in higher eukaryotes; by contrast, no intron-less protein-encoding genomic sequences were seen in the database of Physarum polycephalum – each gene containing, on average, 3.7 introns [NAR (2000) 28 3411–3416]. Splicing of the RNA transcript of a split gene involves cleavage of a precise phosphodiester bond at both ends of each intron (at the exon–intron junctions) – the 5′ and 3′ splice sites; this is followed by the formation of a phosphodiester bond between the exon at the 5′ end of the intron (the 5′ exon) and the exon at the 3′ end (the 3′ exon). Details of the splicing mechanism differ in different types of split gene. Split genes in eukaryotes are considered in (a) to (d), below; split genes in prokaryotes and viruses are considered in (e). (a) Nuclear mRNA introns. In nuclear protein-encoding genes of e.g. Saccharomyces cerevisiae, the introns have been found to contain three CONSENSUS SEQUENCES that are necessary for splicing: GTATGT at the 5′ end of the intron, PyAG at the 3′ end, and TACTAAC (the ‘TACTAAC box’) near the 3′ end. These sequences are those in the DNA strand which has the same sequence as the RNA transcript; they may also be written in terms of the RNA itself, e.g. TACTAAC = UACUAAC. The consensus sequences mentioned above may differ somewhat in other eukaryotes, but nearly all introns of this type have the 5′ terminal GT (the 5′ , left or donor splice site) and the 3′ -terminal AG (the 3′ , right or acceptor splice site); this is the so-called GT. . .AG (or GU. . . AG) rule. Excision of an intron from a pre-mRNA molecule (transcribed by RNA polymerase II) depends on trans-acting factors and 726

spoligotyping transcript. Thus, the very long polycistronic viral RNA transcripts produced in these cells can be spliced in different ways – generating functional mRNAs in which the same 5′ cap and leader sequence is spliced onto different coding sequences. (See also SUBGENOMIC MRNA.) Certain small adenovirus-encoded RNAs (the VA RNAs) which associate with cellular proteins – forming RNP particles – may be involved in splicing viral RNA; VA1 RNA is apparently complementary to splicing junctions in some adenovirus genes. Among archaeans, some tRNA genes contain an intron which, when transcribed, gives rise to a corresponding sequence within the anticodon arm of the pre-tRNA molecule; the position of the intron is generally similar to that in yeast tRNA genes (i.e. on the 3′ side of the anticodon), but in the extreme thermophile Thermoproteus tenax a tRNALeu contains an intron within the anticodon sequence itself, while tRNAAla has an intron in a unique position on the 5′ side of the anticodon in the stem of the anticodon arm [EMBO (1987) 6 523–528]. Bacterial introns appear to be mainly or solely of the autocatalytic type (group I or group II). The bacterial group I introns seem to occur primarily within tRNA genes; they have been found e.g. in the purple bacterium Azoarcus and the cyanobacterium Synechococcus [structure–function relationships of the intron ribozymes of Azoarcus and Synechococcus: NAR (2000) 28 3269–3277], in Anabaena and other cyanobacteria, in Agrobacterium tumefaciens and in Simkania negevensis (a member of the Chlamydiales in which the intron interrupts a 23S rRNA gene). Bacterial group II introns (like group I introns) are mobile genetic elements but are not primarily associated with tRNA genes. Group II inrons have been found e.g. in Lactococcus spp and in Escherichia coli, Pseudomonas alcaligenes and Streptococcus pneumoniae. [Bacterial group II introns (review): Mol. Microbiol. (2000) 38 917–926.] In some cases, splicing in bacteria may occur while the transcript is still bound to a ribosome [splicing and translation in bacteria (perspective): GD (1998) 12 1243–1247]. Splicing in vivo has been demonstrated for a group II intron in the conjugative transposon Tn5397 [JB (2001) 183 1296–1299]. Bacterial introns (of both groups I and II) can propagate by INTRON HOMING. [Barriers to intron promiscuity in bacteria: JB (2000) 182 5281–5289.] split-product vaccine (split-virus vaccine) A VACCINE which contains some of the components of a virus (as opposed to whole virions). split-virus vaccine See SPLIT-PRODUCT VACCINE. splitter See TAXONOMY. spo mutant See ENDOSPORE (sense 1(a)). Spo0A∼P See ENDOSPORE (sense 1). Spo0E See ENDOSPORE (sense 1). Spo0F See ENDOSPORE (sense 1). SpoIIB See ENDOSPORE (figure (a) legend). SpoIID See ENDOSPORE (figure (a) legend). spoIIG See ENDOSPORE (figure (a) legend). SpoIIM See ENDOSPORE (figure (a) legend). SpoIIP See ENDOSPORE (figure (a) legend). SpoIIIE See ENDOSPORE (figure (a) legend). spoilage See BIODETERIORATION. spoligotyping A rapid, PCR-based method for simultaneously detecting and typing strains of the Mycobacterium tuberculosis complex [original description: JCM (1997) 35 907–914]. Essentially, PCR is used to amplify spacer sequences in the direct repeat (DR) locus of the chromosome (which apparently

(the internal guide sequence, IGS) to form a secondary structure that defines the 5′ splice site and holds the 5′ exon in place for the second (exon-ligation) step [Nature (1986) 322 86–89, (discussion 16–17)]; the actual nucleotide sequence of the IGS is different in different introns (i.e. it is not a conserved sequence). Some group I introns are not capable of autocatalytic splicing in vitro in the absence of protein – protein(s) apparently being necessary for the correct folding of the molecule. Certain introns in fungal mitochondrial genes encode a small protein (a maturase) which is apparently synthesized by readthrough from the preceding exon; in at least some cases the maturase is necessary for the splicing of the intron encoding it – possibly being involved in folding the intron to align the splice sites correctly. (c) Group II introns (class II introns). Introns of group II are distinct from those of group I in their conserved sequences and secondary structure (e.g. they have a conserved stem-and-loop or hairpin structure near the 3′ end). Group II introns occur e.g. in fungal mitochondrial protein-encoding genes and in Euglena chloroplast genes. Certain yeast mitochondrial group II introns are self-splicing in vitro in the presence of magnesium ions and spermidine; however, the reaction does not require guanosine or any other nucleotide, and the excised intron initially occurs in the form of a lariat similar to that formed by nuclear pre-mRNA splicing [Cell (1986) 44 213–223, 225–234; 46 557–565]. Group II introns also differ from those in group I in having at their splice sites conserved sequences which are similar to those in nuclear pre-mRNA introns. Nevertheless, splicing of group II introns resembles that of group I introns e.g. in being autocatalytic and in not requiring trans-acting RNA molecules (an IGS may be involved); furthermore, certain group II introns apparently encode ‘maturases’. Thus, group II introns appear to be intermediate in character between group I and nuclear premRNA introns. [Splicing of nuclear pre-mRNA and groups I and II introns (minireview): Cell (1986) 44 207–210.] Interestingly, certain group II introns encode potential products which appear to exhibit homology (over part of their length) with several reverse transcriptases encoded by viruses and transposable elements [Nature (1985) 316 641–643 (discussion 574–575)]. (d) Nuclear tRNA introns. In yeast, at least some nuclear tRNAs contain a single intron in the anticodon arm of the pre-tRNA (see TRNA); the intron contains a sequence that is complementary to the anticodon of the tRNA, and this may allow the anticodon arm to adopt a secondary structure which can be recognized by the splicing enzymes. Splicing requires at least two distinct enzymes. The first catalyses endonucleolytic cleavage with the generation of 5′ -OH ends and 3′ ends bearing a 2′ ,3′ -cyclic phosphate group; the second (an RNA ligase) catalyses exon ligation in an ATP-dependent reaction. (e) Introns in viruses and prokaryotes. Introns have been found in the genomes of certain viruses – including bacteriophages. For example, in phage T4 there are three group I introns: a 598bp intron in gene nrdB (encoding ribonucleotide reductase), a 1033-bp intron in nrdD (= sunY ) (encoding anaerobic ribonucleotide reductase), and a 1016-bp intron in gene td (encoding thymidylate synthase); efficient splicing of td is reported to require a ribosomal function [GD (1998) 12 1327–1337]. All three introns in the T4 genes can self-splice in vitro. [Phage T4 introns: ARG (1990) 24 363–385.] Similar introns also occur in other T-even phages. In adenovirus-infected cells, different patterns of RNA splicing can generate different proteins from the same RNA 727

Spondweni virus

24 3′

DR

25 DR

26 DR

DR

5′

M. tuberculosis H37Rv negative control 1 2 3 4 5 6 7 8 9

SPOLIGOTYPING (simplified protocol; principle, diagrammatic) (see entry). The direct repeat (DR) locus is a distinct region in the chromosome of members of the Mycobacterium tuberculosis complex. It consists of a variable (strain-dependent) number of highly conserved 36-bp direct repeats (DRs) between which are spacer sequences of 34–41 base-pairs in length; the presence/absence and length of spacer sequences varies from strain to strain. (Such variation in the DR locus may result from homologous recombination between different sections of the locus and/or from integration of the insertion sequence IS6110.) In the reference strain M. tuberculosis H37Rv, the chromosome contains 48 DRs; each intervening spacer is identified by a number. Top. Part of a strand of chromosomal DNA in the direct repeat (DR) locus of Mycobacterium tuberculosis. The (non-repetitive) sequences (‘spacers’) which separate the DRs vary in length from 34 to 41 nucleotides and are numbered consecutively. For spoligotyping, all the spacers of a given strain are amplified by PCR. Here, a primer (small arrow) is shown binding to a (conserved) sequence in a DR; primers bind to the same sequence in all other DRs. During cycling, primers are extended across the subsequent spacers. The amplicons from a given test strain are then examined for their ability to hybridize to one row of immobilized oligonucleotides which represent selected spacer sequences of M. tuberculosis strain H37Rv. (In the actual method used by Kamerbeek et al (1997) there were 43 25-mer oligonucleotides in each horizontal row; these oligonucleotides represented spacers 1–19, 22–32 and 37–43 of M. tuberculosis strain H37Rv, and spacers 20–21 and 33–36 of M. bovis BCG.) Below. Simplified protocol showing a membrane to which has been covalently bound 11 identical horizontal rows of oligonucleotides; in each row the oligonucleotides represent sequences from selected spacers of M. tuberculosis strain H37Rv. Each horizontal row was exposed to amplicons from one of the test strains; hybridization (dark spot) has occurred when a DR spacer in the test strain matched the sequence of a spacer in strain H37Rv. Note clustering of strains 6, 7 and 8 (the kind of result which might be obtained with a group of strains isolated from a single outbreak of disease). Reproduced from Figure 7.7, page 195, in DNA Methods in Clinical Microbiology (ISBN 07923-6307-8), Paul Singleton (2000), with kind permission of Kluwer Academic Publishers, Dordrecht, The Netherlands.

occurs only in members of the M. tuberculosis complex); spacer amplicons from the test strain are then hybridized to a set of oligonucleotides which represent spacer sequences from a standard reference strain (M. tuberculosis strain H37Rv). (The name ‘spoligotyping’ is thus a contraction of ‘spacer oligotyping’.) For a given strain, the pattern of matching and mis-matching of spacers (compared with those of the reference strain) is the spoligotype. A simplified form of the method is outlined in the figure. In addition to typing strains of the M. tuberculosis complex, spoligotyping is also useful for distinguishing between M. tuberculosis and M. bovis – a task which can be difficult by traditional methods; such differentiation is based on the absence, in M. bovis, of the five 3′ outermost spacers (which are present in M. tuberculosis strain H37Rv – and in a large number of other strains of this species which have been examined). This feature of spoligotyping is particularly useful as M. bovis commonly contains only a single copy of the insertion sequence

IS6110 – making it difficult to distinguish between strains of M. bovis by IS6110 fingerprinting. Spoligotyping may help to promote investigations on the animal reservoirs of M. bovis which are potential sources of infection for both animals and humans. Spoligotyping has also been used for checking the validity of IS6110 -based typing of M. tuberculosis [JCM (1999) 37 788–791] and for investigating laboratory cross-contamination [JCM (1999) 37 916–919]. [Spoligotype database of Mycobacterium tuberculosis (biogeographic distribution of shared types, and epidemiological and phylogenetic perspectives): EID (2001) 7 390–396.] Spondweni virus See FLAVIVIRIDAE. spongiform encephalopathies See SUBACUTE SPONGIFORM ENCEPHALOPATHIES. Spongilla See ZOOCHLORELLAE. spongiome See CONTRACTILE VACUOLE. spongioplasm See CONTRACTILE VACUOLE. 728

spore ball basipetally formed chains; in many fungi (e.g. Mucor ) the sporangium contains a COLUMELLA. A sporangium may be deciduous at maturity (e.g. in Dictyuchus) or it may remain attached to the sporangiophore (e.g. in Saprolegnia); the spores may be released via a pore or by dissolution of the sporangial wall. In e.g. Pilobolus the entire sporangium is forcibly discharged. (See also meiosporangium and mitosporangium under ALLOMYCES, and zygosporangium under ZYGOSPORE.) (2) (bacteriol.) The cell in which an ENDOSPORE is formed. (3) (bacteriol.) That part of a cell which subsequently develops into an endospore. (4) (bacteriol.) In e.g. Actinoplanes and members of the MYXOBACTERALES: a specialized structure containing one or more spores. spore A differentiated form of an organism which may be (a) specialized for dissemination; (b) produced in response to, and characteristically resistant to, adverse environmental conditions; and/or (c) produced during or as a result of an asexual or sexual reproductive process. (Not all microorganisms can produce spores.) A spore may be unicellular (i.e., it may contain only one protoplast), bicellular, or multicellular; it may be thick-walled or thin-walled, pigmented or non-pigmented, motile or nonmotile. Under suitable conditions, disseminative and resistant forms of spore typically give rise to a vegetative organism(s); a spore formed in a reproductive process may e.g. give rise to a vegetative organism or act as a gamete. Bacterial spores. Bacterial ENDOSPORES (q.v.) are resistant (and may be disseminative) forms rather than reproductive forms, while the EXOSPORES formed e.g. by species of the ACTINOMYCETALES (q.v.) are characteristically reproductive and disseminative forms. (See also myxospores in MYXOBACTERALES.) Fungal spores. See e.g. ASCOSPORE; AZYGOSPORE; BALLISTOSPORE; BASIDIOSPORE; CHLAMYDOSPORE; CONIDIUM (and SACCARDOAN SYSTEM); GEMMA; OIDIUM; SPORANGIOSPORE; STATISMOSPORE; THALLOSPORE; ZYGOSPORE. (See also UREDINIOMYCETES and USTILAGINALES.) Some fungal spores exhibit DORMANCY. Exogenous dormancy is that due to the effects of environmental conditions; germination occurs only under conditions favourable for vegetative growth. Endogenous (= constitutive) dormancy is due to internal factors; these may include (a) the presence of a permeability barrier to nutrients, (b) the existence of a (reversible) metabolic block, and/or (c) the presence of an endogenous chemical inhibitor of germination. The self-inhibitor in e.g. uredospores of Puccinia graminis is methyl-cis-ferulate (which inhibits removal of the germination plug in the spore wall), while in the uredospores of some other rusts the inhibitor is methylcis-3,4-dimethoxycinnamate (which blocks initiation of the germ tube). In general, self-inhibitors may account for the low rate of germination of spores in masses; the leaching of inhibitor may account for the enhancement in germination when such spores are washed with water. Dormancy can be broken by activation e.g. by certain chemical agents (activators) that include detergents and organic solvents; by heating the spores to ca. 50–60° C for 10–20 min (e.g. Neurospora spp); or by subjecting the spores to cold (e.g. teliospores of Puccinia graminis). Some spores can be induced to germinate by damaging the spore wall. [Physiology and biochemistry of fungal sporulation: ARPpath. (1982) 20 281–301.] Protozoal spores. See e.g. ASCETOSPORA; MICROSPORA; MYXOZOA. spore ball See USTILAGINALES.

Spongospora See PLASMODIOPHOROMYCETES and POWDERY SCAB. spontaneous generation Syn. ABIOGENESIS. spontaneous mutation (background mutation) Any MUTATION which occurs ‘naturally’, i.e., in the absence of any obvious external MUTAGEN; such mutations normally occur at low frequencies (cf. MUTATOR GENE). Mutations which are apparently spontaneous may arise e.g. as a result of the effects of environmental mutagens (e.g. natural gamma radiation, ULTRAVIOLET RADIATION, heat) or of endogenous mutagens produced during metabolism (e.g. peroxides, and possibly the endogenous alkylating agent S-adenosylmethionine). However, mutations are usually regarded as truly spontaneous only when they result from errors in DNA replication or repair, or from chemical reactions which tend to occur spontaneously in the DNA itself. For example, deamination of bases and depurination (or, less commonly, depyrimidination) of nucleotides are spontaneous reactions of DNA; thus, e.g., deamination of cytosine to uracil leads to mutagenesis since, during subsequent DNA synthesis, uracil pairs with adenine (resulting in a G·C-to-A·T transition). (cf. URACIL-DNA GLYCOSYLASE.) Certain regions of a given DNA molecule may be particularly prone to spontaneous mutagenesis: e.g., in Escherichia coli such ‘hotspots’ occur e.g. at sites occupied by the modified base 5-methylcytosine (see DNA METHYLATION); spontaneous deamination of this base generates thymine, resulting in a G·C-to-A·T transition. (The thymine residue, being a normal component of DNA, cannot be recognized by any DNA REPAIR system.) Other hot-spots may contain e.g. DIRECT REPEATS or INVERTED REPEATS, and these are apparently associated with insertions or deletions (and hence e.g. FRAMESHIFT MUTATIONS). In E. coli, error-prone DNA repair (see SOS SYSTEM) is apparently responsible for a low level of random (non-targeted) mutagenesis. Deletions, insertions, inversions etc may also be attributable to the activities of TRANSPOSABLE ELEMENTS. [Analysis of spontaneous mutations in the lacI gene of E. coli: JMB (1986) 189 273–284.] spoonleaf A disease of redcurrants caused by the raspberry ringspot virus (a NEPOVIRUS). spora That fraction of the particulate matter in AIR (q.v.) consisting of, or including, SPORES. sporabola (mycol.) The trajectory of a forcibly-discharged basidiospore. sporadin The gametocyte form of a gregarine. sporangiole Syn. SPORANGIOLUM. sporangiolum (sporangiole) (mycol.) A SPORANGIUM-like structure containing a single spore or a small number of spores; it characteristically lacks a columella. Some fungi form both sporangiola and sporangia (see e.g. Choanephoraceae in MUCORALES). The sporangiolum may be an evolutionary intermediate between the sporangium and the CONIDIUM. sporangiomycin See THIOSTREPTON. sporangiophore A modified or undifferentiated, simple or branched hypha which bears at least one SPORANGIUM or SPORANGIOLUM. In some fungi (e.g. Pilaira, Pilobolus) the sporangiophores are positively phototropic. sporangiospore (mycol.) A thin-walled, motile or non-motile spore formed in a SPORANGIUM or in a SPORANGIOLUM; such spores are characteristic of the lower fungi. (cf. CONIDIUM.) sporangium (1) (mycol.) In some lower fungi: a sac-like structure whose contents are converted into motile or non-motile spores (sporangiospores). (cf. MEROSPORANGIUM; SPORANGIOLUM; ZOOSPORANGIUM.) Sporangia are often globose or elongated, and may occur e.g. singly and terminally on a sporangiophore, in clusters on branched sporangiophores, or (e.g. in Albugo) in 729

spore coat sporoactinomycetes A category within the order ACTINOMYCETALES which includes spore-forming organisms that are characterized by a morphology more complex than that of the NOCARDIOFORM ACTINOMYCETES. Sporobolomyces A genus of fungi (see SPOROBOLOMYCETACEAE) which form spheroidal, ovoid or elongate budding yeast cells; some species can form pseudomycelium and true mycelium. The cell walls lack xylose, and growth on malt agar is pink, red or orange due to the presence of carotenoid pigments (cf. BULLERA). Ballistospores are formed on hyphal and yeast cells; they are typically bilaterally symmetrical (e.g. reniform or sickle-shaped) and develop obliquely at the tips of branched or unbranched sterigmata. Metabolism is strictly respiratory. NO3 − is assimilated by S. holsaticus, S. puniceus (formerly Candida punicea), S. roseus and S. salmonicolor, but not by S. albo-rubescens, S. gracilis or S. shibatanus. Species may be anamorphs of SPORIDIOBOLUS spp; they have been isolated e.g. from plant material, from beer (S. roseus), etc. [Book ref. 100, pp. 911–920.] Sporobolomycetaceae A family of anamorphic fungi (see BLASTOMYCETES) which are characterized by the formation of BALLISTOSPORES. The organisms, which have basidiomycetous affinities, form budding yeast cells; some can form pseudomycelium and/or true mycelium. The family includes BULLERA and SPOROBOLOMYCES. (See also MIRROR YEASTS.) sporocarp Syn. FRUITING BODY. Sporochnus See PHAEOPHYTA. sporocladium See KICKXELLALES. sporocyst (1) In most coccidia: a sac, formed within an oocyst, containing one or more (often 2, 4 or 8) sporozoites; there may be one or more sporocysts per oocyst. Sporocysts may be ovoid, spherical or elongated, and those of some species have a STIEDA BODY. (See also EIMERIORINA and SPORULATION.) (2) See MONOCYSTIS. Sporocytophaga A genus of GLIDING BACTERIA of the CYTOPHAGALES. The cells are pigmented rods, up to ca. 8 µm long, from which resting cells (microcysts) develop; the microcyst is a spherical, desiccation-resistant structure which has a thick capsule. The organisms are chemoorganotrophic; growth occurs aerobically on cellulose (see CELLULASES), cellobiose, or glucose (mannose is used by some strains). Growth is inhibited by high concentrations of organic nitrogen or of sugars. sporodochium A pad- or cushion-like fungal STROMA which bears a surface layer of conidiophores. Sporodochia are formed e.g. by species of Fusarium and Nectria. sporogony (1) The division of a zygote (= sporont ) into a number of haploid cells (sporozoites). (2) The (mitotic) division of a cell (sporont) into a number of spores or sporozoites. (3) A process which involves the formation and fusion of gametes and the division of the zygote to form spores or sporozoites. Sporolactobacillus A genus of Gram-positive, chemoorganotrophic, microaerophilic, catalase-negative, ENDOSPORE-forming bacteria which occur e.g. in soil. Cells: flagellated rods, ca. 1 × 3–5 µm. Lactic acid is formed, anaerogenically, from e.g. glucose and other sugars and from sugar alcohols. Type species: S. inulinus. Sporomusa A genus of Gram-negative, anaerobic, ENDOSPOREforming bacteria isolated e.g. from river-mud, soil, waste water etc. Cells: mainly banana-shaped, motile (with up to 15 lateral flagella). The organisms can use e.g. N-methyl compounds (e.g. betaine, sarcosine), primary alcohols, hydroxy fatty acids, and 2,3-butanediol as substrates, acetate being the characteristic product of metabolism; H2 and CO2 are converted to acetate.

spore coat See ENDOSPORE (sense 1 (a)). spore print (mycol.) A deposit of spores formed when the cap of a mature agaric is left, gills-down, on a piece of plain white paper; it is useful e.g. for determining spore colour. spore stains See e.g. ENDOSPORE STAINS. spore strip A strip of filter paper, foil etc on which a suspension of endospores (e.g. those of Bacillus stearothermophilus) has been allowed to dry; it is used e.g. for monitoring the performance of an AUTOCLAVE. [Commercial spore strip performance: AEM (1982) 44 12–18.] sporic meiosis MEIOSIS in a life cycle characterized by an ALTERNATION OF GENERATIONS. Sporichthya A genus of bacteria (order ACTINOMYCETALES, wall type I) which occur e.g. in soil. The organisms form an aerial mycelium consisting of sparingly-branched hyphae (0.5–1.2 µm in diameter, up to ca. 25 µm in length) which are anchored to the medium by holdfasts; no substrate mycelium is formed. Aerial hypae divide into coccoid and rod-shaped forms which, in the presence of water, give rise to motile (flagellated) propagules. Growth occurs at room temperatures and at 37° C. Type species: S. polymorpha. [Book ref. 73, pp. 101–102.] sporicide Any chemical agent which inactivates spores (particularly bacterial ENDOSPORES) irreversibly. sporidesmins Cyclic depsipeptide MYCOTOXINS produced by Pithomyces chartarum. Sporidesmins can cause a mycotoxicosis, ‘facial eczema’, in sheep or cattle grazing pastures contaminated with P. chartarum; facial eczema occurs in parts of Australasia, Africa and the USA. Symptoms, which are strongly dose-dependent, include e.g. anorexia, diarrhoea, dehydration, photosensitivity, jaundice, and inflamed oedematous swellings on the lips, face and vulva; death may occur. Thiabendazole has been used to control the fungus in pastures. Sporidesmin and sporidesmin E inhibit the growth of certain bacteria (e.g. Bacillus subtilis) and are extremely toxic (at 2 (cf. MICROCOCCUS). Cells: spherical, ca. 1 µm diam., occuring in characteristic clusters (the name Staphylococcus derives from the Greek for ‘bunch of grapes’). Non-motile. Orange/yellow CAROTENOID pigments occur in S. aureus and in strains of some other species. A CAPSULE may be present. (Capsulation can e.g. interfere

with phage typing, prevent the clumping factor reaction (in the COAGULASE TEST), and affect the morphology of the colony.) Most species appear to contain only a- and b-type CYTOCHROMES (c-type cytochromes occur in S. sciuri ) [Book ref. 44, p 399]. Staphylococci occur as commensals/parasites and pathogens in man and other animals. Diseases caused by species of Staphylococcus in man and animals include e.g. ARTHRITIS, BLACK POX, BOIL, BRONCHITIS, BUMBLEFOOT, CARBUNCLE, CYSTITIS, ENDOCARDITIS, FOOD POISONING, IMPETIGO, JOINT-ILL, KERATOCONJUNCTIVITIS, MENINGITIS, OSTEOMYELITIS, PNEUMONIA, SCALDED SKIN SYNDROME and TOXIC SHOCK SYNDROME. (See also EAR MICROFLORA, GENITOURINARY TRACT FLORA, RESPIRATORY TRACT MICROFLORA, SKIN MICROFLORA, VAGINA MICROFLORA.) GC%: ca. 30–39. Type species: S. aureus. Classification of the staphylococci. Staphylococci are divided into COAGULASE-positive and coagulase-negative strains. Strains of S. aureus and S. intermedius are coagulase-positive, as are some strains of the animal pathogen S. hyicus subsp hyicus; most species of Staphylococcus are coagulase-negative. In terms of pathogenic potential, S. aureus is considered to be the most important species; however, other species, including a number of coagulase-negative staphylococci (CNS), are also associated with disease, often as opportunist pathogens. Species include: S. albus. See S. epidermidis. S. aureus. A major pathogen of man and other animals. The cells, ca. 1 µm in diam., are often pigmented (see STAPHYLOXANTHIN), particularly in freshly isolated strains. The cell wall usually contains ribitol teichoic acids, and most strains form PROTEIN A; the PEPTIDOGLYCAN contains little or no L-serine. The cell wall lipoteichoic acid is a virulence factor: it acts as an adhesin which binds to fibronectin (a glycoprotein component of e.g. epithelial cells). Protein adhesins of S. aureus bind to mammalian targets such as collagen and fibronectin [TIM (1998) 6 484–488]. (See also SORTASE.) The expression of virulence factors by S. aureus is controlled by various mechanisms which involve e.g. the AGR LOCUS. The expression of certain virulence factors, including exotoxin, appears to involve a TWO-COMPONENT REGULATORY SYSTEM that responds to levels of environmental oxygen [JB (2001) 183 1113–1123]. In general, the expression of virulence factors in S. aureus depends on the growth phase and/or on conditions of growth. Regulation of exotoxins and wall-associated proteins (e.g. PROTEIN A) is complex [FEMS Reviews (2004) 28 183–200]. The organism forms a thermostable DEOXYRIBONUCLEASE, and produces both free coagulase and clumping factor (see COAGULASE and COAGULASE TEST). [Evaluation of the STAPHYLOSLIDE and other agglutination tests: JCM (1985) 21 726–729.] All strains coagulate e.g. human and rabbit plasma. Glucose is usually fermented to DL-lactic acid, and lactose metabolism involves the tagatose 6-phosphate pathway (see Appendix III(a)). Mannitol is utilized aerobically and anaerobically, and maltose is utilized aerobically. VP +ve. (See also HYALURONATE LYASE and PHOSPHATASE.) S. aureus is characteristically sensitive to NOVOBIOCIN (MIC 75° C. Cells: cocci, ca. 1 µm diam. T. celer is polarly flagellate. GC%: ca. 40–60%. [Strains of Thermococcus from sites in the Pacific Ocean: FEMS Ecol. (2001) 36 51–60.] thermocycler (thermal cycler) An instrument used in certain nucleic-acid-amplification techniques (LCR and PCR) for automatically making the cyclical changes in temperature. Such instruments can simultaneously process a number of reaction mixtures and can usually be programmed for any of a range of time/temperature protocols. The way in which reaction mixtures are heated and cooled is based on one of two methods. In the Peltier system, each reaction mixture is processed in a thin-walled tube which fits snugly in a hole in a metal block; temperature cycling involves heating and cooling the block according to the particular protocol. Cycling times are affected by the rate at which the block can be heated and cooled; in one commercial instrument, heating can occur at a rate of up to 3° C/second while the maximum rate of cooling is ∼2° C/second. In these (open-tube) methods the problem of evaporation (loss of sample) is tackled in two ways. One approach involves the use of an oil overlay. Another solution is to use a heated lid cycler in which a temperature of up to 120° C is maintained over the sample tubes. Alternatively, the sample may be sealed into a capillary glass tube which is heated and cooled by means of a forced air current; in the LightCycler (Roche), the air temperature around each tube can be changed at a rate of 20° C/second, permitting rapid cycling. Some instruments (including the LightCycler) incorporate a system for detecting and/or quantifying the products of amplification. Thermodiscus A genus of prokaryotes of the order THERMOPROTEALES. Cells: disc-shaped, ca. 0.3–3.0 µm diameter, ca. 0.2 µm thick. thermoduric (thermotolerant) Refers to an organism which can survive temperature–time combinations that are normally lethal for many or most vegetative microorganisms. In dairy microbiology the term refers to those organisms which survive PASTEURIZATION (e.g., many strains of Microbacterium can survive 70–80° C/15 minutes). (See also THERMOPHILE.) Thermofilum A genus of chemolithoheterotrophic prokaryotes (order THERMOPROTEALES) which occur in Icelandic solfataras; the organisms metabolize e.g. peptides. Cells: rods or filaments, ca. 0.2 × 5–100 µm. T. pendens is non-flagellated. GC% ca. 57. 770

Thiobacillus positive charge and is usually supplied commercially as thiamine chloride hydrochloride (‘thiamine hydrochloride’). The coenzyme form is thiamine pyrophosphate (TPP, cocarboxylase). TPP functions in decarboxylation reactions (e.g. pyruvate → acetaldehyde); in oxidative decarboxylations – e.g. (in conjunction with LIPOIC ACID) of pyruvate and 2-oxoglutarate [see Appendix II(a)]; in a-ketol formation – e.g. acetoin formation [Appendices III(c) and III(f)]; in transketolase and phosphoketolase reactions [Appendices I(b) and III(b), respectively]; etc.

A genus of thermophilic prokaryotes (order found e.g. in Icelandic solfataras. Cells: rods or filaments, ca. 0.5 × 1–80 µm. Chemolithoautotrophic and/or chemolithoheterotrophic, according to species; heterotrophs use e.g. ethanol, formate, glucose, methanol, sucrose. Energy is obtained by SULPHUR RESPIRATION. Species include T. neutrophilus (obligate autotroph) and T. tenax (facultative autotroph). GC%: ca. 55–56. thermospermine See POLYAMINES. thermotaxis A TAXIS in which the stimulus is a temperature gradient. thermotherapy (plant virol.) See PLANT VIRUSES. Thermothrix A genus of thermophilic bacteria. T. thiopara is a facultatively anaerobic, rod-shaped or filamentous organism which occurs in hot springs (45–75° C); it is facultatively chemolithoautotrophic, electron donors including e.g. sulphide and elemental sulphur. [Ecology and metabolism: AAM (1986) 31 233–270.] Thermotoga See BACTERIA (taxonomy). Thermotogales See BACTERIA (taxonomy). thermotolerant Syn. THERMODURIC. Thermus A genus (incertae sedis) of aerobic, chemoorganotrophic, thermophilic, Gram-negative bacteria which occur e.g. in hot springs. Cells: non-motile rods, 0.5–0.8 × 5.0–10.0 µm, or filaments, which typically contain yellow, orange or red carotenoid pigments and novel POLYAMINES. The cell ultrastructure resembles that of other Gram-negative bacteria, but the ‘outer wall’ (external to the peptidoglycan layer) seems to be more substantial than the typical outer membrane of Gramnegative cells; the peptidoglycan lacks DAP, contains ornithine, and has a high proportion of glycine and glucosamine. Most strains give rise to ‘rotund bodies’: membrane-enclosed spherical aggregates of cells (average: 14 cells per aggregate), ca. 10–20 µm in diameter; the limiting membrane of a rotund body is formed by fusion of the outer walls of adjacent cells at the periphery of the body, the inward-facing surface of these cells lacking an outer wall. Metabolism is respiratory (oxidative), with O2 as terminal electron acceptor. Carbon sources include e.g. sugars and organic acids; nitrogen sources: e.g. NH4 + , amino acids. Optimum growth temperature: ca. 66–75° C; optimum pH: ca. 7.0. Oxidase +ve. Catalase +ve GC%: ca. 61–71. Type species: T. aquaticus. [Book ref. 22, pp. 333–337.] [Proposed species – T. ruber (revised name): IJSB (1984) 34 498–499.] theront In the polymorphic life cycles of certain protozoa: a cell which ‘searches for’ or ‘hunts’ a new host organism or a source of food; see e.g. ICHTHYOPHTHIRIUS. q See TEMPERATURE COEFFICIENT. q (theta) replication Syn. CAIRNS’ MECHANISM. THF TetrahydroFOLIC ACID. thiabendazole 2-(4′ -Thiazolyl)-benzimidazole. Originally used as an anti-helminthic agent, thiabendazole is now regarded as an efficient fungicide and is used e.g. to protect against seedborne smuts and bunts of cereals, and to prevent rots of stored fruit and vegetables. Thiabendazole has been widely used as the principal agent for the protection of stored citrus fruit against Penicillium digitatum and P. italicum; however, thiabendazoleresistant strains of these and other citrus rot fungi have emerged [Book ref. 121, pp. 149–162]. (See also BENZIMIDAZOLES; GANGRENE (sense 2); SPORIDESMINS.) thiacetazone See THIOSEMICARBAZONES. thiamine (thiamin; vitamin B1 ; aneurin) A water-soluble VITAMIN: 3-(2-methyl-4-amino-5-pyrimidinylmethyl)-5-(b-hydroxyethyl)-4-methylthiazole (see figure); the molecule carries a net Thermoproteus

THERMOPROTEALES)

NH2 N H3C

S CH2

N

N+ CH3

CH2

CH2OH

THIAMINE

Microorganisms which require exogenous thiamine (or one or both of the pyrimidine and thiazole precursors) include e.g. Euglena spp, certain fungi (e.g. Phycomyces blakesleeanus, Phytophthora spp, Trichophyton spp, many yeasts), some bacteria (e.g. Lactobacillus spp, Leuconostoc spp, Staphylococcus aureus), and various protozoa (e.g. Acanthamoeba castellanii, Crithidia fasciculata, Tetrahymena spp). Thielaviopsis See HYPHOMYCETES; see also FOOTROT (sense 2). thienamycin An antibiotic produced by Streptomyces cattleya and by S. penemifaciens; it is a CARBAPENEM (see b-LACTAM ANTIBIOTICS for structure) in which R′ = CH3 .CHOH and R′′ = NH2 .(CH2 )2 .S. Thienamycin binds to the PENICILLIN-BINDING PROTEINS of Escherichia coli (preferentially to PBP-2); it is highly active against Gram-positive and Gram-negative bacteria (including species of Pseudomonas) and is resistant to many b-LACTAMASES, but is chemically unstable. Many naturally occurring and semi-synthetic derivatives of thienamycin have been isolated; the N-formimidoyl derivative (imipenem; MK-0787) is less unstable than thienamycin, is resistant to many b-lactamases, has a similar level of activity against most bacteria, and is more active against Pseudomonas spp. [Imipenem (review): AIM (1985) 103 552–560.] Thi´ery staining A procedure for detecting polysaccharides by electron microscopy. thigmotaxis A TAXIS in which the stimulus is ‘touch’ (physical contact); an organism may move towards the contact (positive thigmotaxis) or away from it (negative thigmotaxis). thimerosal Syn. THIOMERSAL. thin-layer chromatography See CHROMATOGRAPHY. Thiobacillus A genus of Gram-negative, obligately or facultatively chemolithoautotrophic (or mixotrophic) bacteria which occur e.g. in soil, marine muds, mine drainage and hot springs. The cells are typically polarly flagellated rods, ca. 0.5 × 1.0–3.0 µm. Most species obtain energy by oxidizing sulphur and/or reduced sulphur compounds (sulphide, sulphite and thiosulphate); in at least some cases c-type cytochromes are involved. GC%: ca. 50–68. Type species: T. thioparus. Thiobacillus A2. See T. versutus (below). T. delicatus. Non-motile. Facultative anaerobe. Capable of nitrate respiration. Electron donors: e.g. sulphide, thiosulphate. Optimum temperature: 30–35° C. Optimum pH: 5.5–6.0. [IJSB (1984) 34 139–144.] 771

Thiocapsa T. denitrificans. Electron donors: e.g. sulphide and thiosulphate. Under aerobic conditions oxygen is the electron acceptor; anaerobically, nitrate, nitrite or nitrous oxide can function as electron acceptor, and is reduced to nitrogen. Optimum pH: 6–8. T. ferrooxidans. Aerobic; growth also occurs anaerobically with ferric ions as electron acceptor for the oxidation of reduced sulphur compounds. Electron donors include sulphur, thiosulphate, sulphide and ferrous ions. Capable of NITROGEN FIXATION. Optimum growth temperature: ca. 20° C. Growth occurs within the approximate pH range 1.4–6.0. (See also LEACHING.) [Molecular genetics of T. ferrooxidans: MR (1994) 58 39–55.] T. thiooxidans. Electron donors include e.g. thiosulphate and (particularly) elemental sulphur. Optimum pH: ca. 2–4; growth occurs within the approximate range 0.5–6.0. Can cause RUBBER SPOILAGE. (See also LEACHING.) T. thioparus. Motile rods. Electron donors include sulphide and thiosulphate; some strains can use thiocyanate (CNS− ). A sulphur-containing pellicle may be formed on thiosulphatecontaining liquid media. Nitrate is reduced to nitrite during anaerobic growth. Optimum growth temperature: ca. 28° C. Optimum pH: ca. 6–8; growth ceases below ca. pH 4.5. T. versutus (formerly Thiobacillus A2). A species capable of chemolithoautotrophic or mixotrophic growth. Oxidation of organic substrates (but not inorganic sulphur compounds) can be coupled to the reduction of nitrate. Other species include T. intermedius and T. perometabolis [IJSB (1984) 34 139–144], T. acidophilus, T. neapolitanus, T. novellus and T. organoparus. [Media and culture: Book ref. 45, pp. 1023–1036.] Thiocapsa A genus of photosynthetic bacteria (family CHROMATIACEAE). The cells are non-motile cocci; in addition to various carotenoids, T. roseopersicina (1.2–3.0 µm) contains Bchl a, and T. pfennigii (ca. 1.5 µm) contains Bchl b – cell suspensions typically being reddish and orange-brown, respectively. In T. pfennigii the pigments occur in tubular intracytoplasmic membrane systems. Gas vacuoles are absent. T. roseopersicina is moderately tolerant of organic pollution, and may give rise to reddish blooms in sewage lagoons; it is capable of chemoorganotrophic growth under microaerobic conditions in the dark. thioctic acid Syn. LIPOIC ACID. Thiocystis See CHROMATIACEAE. Thiodictyon See CHROMATIACEAE. thioglycollate broth See e.g. BREWER’S THIOGLYCOLLATE MEDIUM. thiol-activated cytolysins (SH-activated cytolysins) A class of cytolysins, formed by certain bacteria, which are active only in the reduced state, and which can be (reversibly) activated by thiols; the cytolytic activity of these toxins is confined to those cells (including e.g. erythrocytes) whose cytoplasmic membrane contains cholesterol. Thiol-activated cytolysins are formed by species of the (Gram-positive) bacteria Bacillus, Clostridium, Listeria and Streptococcus. (A thiol-activated cytolysin was reported to be formed by the (Gram-negative) species Klebsiella pneumoniae [CJM (1985) 31 297–300].) The thiol-activated cytolysins are proteins of ∼47–60 kDa; they are optimally active at similar values of pH and temperature, they cross-react serologically, and their haemolytic activity is irreversibly lost in the presence of cholesterol or stereochemically related sterols. The thiol-activated cytolysins are pore-forming agents. They bind reversibly, in a temperature-independent manner, to cholesterol-containing membranes, and oligomerize to form (typically) ring-shaped formations (pores in the membrane) of

up to ∼40 nm in diameter. Oligomerization is temperaturedependent, activity being reduced at low temperatures. Studies with animal models have indicated that at least some of the toxins (e.g. pneumolysin) can contribute to virulence. The thiol-activated cytolysins include: alveolysin (Bacillus alvei ) bifermentolysin (Clostridium bifermentans) botulinolysin (C. botulinum) cereolysin (B. cereus) chauveolysin (d-toxin of C. chauvoei ) histolyticolysin (e-toxin of C. histolyticum) ivanolysin (Listeria ivanovii ) laterosporolysin (B. laterosporus) listeriolysin (L. monocytogenes) oedematolysin (d-toxin of C. novyi ) perfringolysin (q-toxin of C. perfringens) pneumolysin (Streptococcus pneumoniae) seeligerolysin (L. seeligeri ) septicolysin (d-toxin of C. septicum) sordelliolysin (C. sordelli ) STREPTOLYSIN O (q.v.) tetanolysin (C. tetani ) thuringiolysin (B. thuringiensis) [Thiol-activated cytolysins: RMM (1996) 7 221–229.] thiol protease See PROTEASES. thiomersal (merthiolate; thimerosal) Sodium ethylmercurithiosalicylate, C2 H5 .Hg.S.C6 H4 .COONa. An antibacterial and antifungal agent used as a preservative e.g. in biological laboratory reagents; it is effective in low concentrations (e.g. 0.01–0.02%). Thiomicrospira A genus of bacteria which occur e.g. in estuarine muds and in the vicinity of HYDROTHERMAL VENTS. Cells: curved or spiral rods; many strains are motile by means of a single polar flagellum. The organisms resemble THIOBACILLUS in general physiology. T. denitrificans and T. pelophila are both obligate chemolithotrophs. [Culture: Book ref. 45, pp. 1023–1036; T. crunogena, an obligately chemolithoautotrophic species from a hydrothermal vent: IJSB (1985) 35 422–424.] thionin (Lauth’s violet) A blue–purple dye structurally related to METHYLENE BLUE. (See also BRUCELLA.) Thiopedia See CHROMATIACEAE and COENOBIUM. thiopeptin A peptide antibiotic related to THIOSTREPTON; it is active against e.g. Streptococcus bovis. Thiopeptin inhibits experimentally-induced lactic ACIDOSIS in ruminants. thiophanate-methyl (1,2-bis(3-methoxycarbonyl-2-thioureido) benzene) An agricultural antifungal agent (see BENZIMIDAZOLES) which is effective e.g. against Rhizoctonia solani infections in seedlings, Pyricularia oryzae in rice, eyespot and Rhynchosporium infection in cereals, and black spot of roses; it also has some effect in controlling clubroot in crucifers. thiophene-2-carboxylic acid hydrazide test Syn. T2H TEST. a-thiophosphoryl dATP See SDA. Thioploca A genus of GLIDING BACTERIA (see CYTOPHAGALES) which occur e.g. in sulphide-containing muds (freshwater to marine). The organisms occur as sheathed fascicles, each fascicle (macroscopic in some species) consisting of a longitudinally arranged bundle of filaments; individual filaments (ca. 1–10 µm wide; wider in marine species) can glide in the sheath and emerge from it. In at least some species metabolism involves oxidation of sulphide. Sulphur is deposited intracellularly. Type species: T. schmidlei. Other species: e.g. T. ingrica from lake sediments [IJSB (1984) 34 344–345], T. araucae, T. chileae (marine benthic species) [IJSB (1984) 34 414–418]. 772

three-for-one model Strains from a HYDROTHERMAL VENT have vacuoles that seem not to be involved in the accumulation of nitrate for use in anoxic conditions [AEM (2004) 70 7487–7496]. thioredoxin A heat-stable 109-amino-acid protein which occurs ubiquitously in cells; in Escherichia coli it is encoded by the trxA gene. Thioredoxin functions as a hydrogen donor e.g. for the reduction of ribonucleotides by ribonucleotide reductase (see nucleotide), in assimilatory sulphate reduction, in the reduction of thiol groups in proteins, etc; the active site of the oxidized form of thioredoxin contains a disulphide bridge between two cysteine residues, and this disulphide bridge can be reduced by the enzyme thioredoxin reductase, using NADPH as hydrogen donor. Thioredoxin also functions as an essential component of BACTERIOPHAGE T7-specific DNA polymerase, and is required for filamentous phage assembly (see INOVIRUS). Thioredoxin can be released from E. coli cells by osmotic shock, and may be located at the ADHESION SITES in the cell envelope. Thiorhodaceae See CHROMATIACEAE. Thiosarcina See CHROMATIACEAE. thiosemicarbazones Derivatives of thiosemicarbazone (R2 C= N.NH.CS.NH2 ) – e.g. thiacetazone: 4-acetamidobenzaldehyde thiosemicarbazone – have been utilized as chemotherapeutic agents against tuberculosis. The earlier drugs have been largely superseded by less toxic drugs, but 2-acetylpyridine thiosemicarbazones were synthesized for potential use in antiparasite (e.g. antimalarial), antibacterial and antineoplastic therapy; they apparently function by inhibiting ribonucleoside diphosphate reductase. Some of these thiosemicarbazones also have antiviral activity, inactivating the ribonucleoside diphosphate reductase of e.g. herpes simplex virus type 1 in a time-dependent manner [JGV (1986) 67 1625–1632]. (See also ISATIN-b-THIOSEMICARBAZONE.) Thiospira A genus of Gram-negative, helical, polarly flagellated bacteria which occur in freshwater and marine H2 S-containing habitats; the cells typically contain globules of sulphur. Thiospirillum A genus of photosynthetic bacteria (family CHROMATIACEAE). The cells are spiral, ca. 10–100 µm long by up to 4 µm wide, and motile by lophotrichous flagella; in addition to various carotenoids, they contain Bchl a – cell suspensions being typically orange-brown. All strains are strict anaerobes and require sulphide and vitamin B12 . thiostrepton A sulphur-containing peptide antibiotic, produced by Streptomyces azureus, which is active against Gram-positive bacteria and certain members of the Archaea (methanogens); it binds strongly to the 50S ribosomal subunit and inhibits protein synthesis. Antibiotics which appear to be structurally and functionally related include siomycin, sporangiomycin and THIOPEPTIN. thiosulphate A salt of thiosulphuric acid; the thiosulphate ion is S2 O3 2− . Thiosulphate can be used as a substrate for lithotrophic metabolism e.g. by Thiobacillus spp, and as an electron acceptor e.g. by SULPHATE-REDUCING BACTERIA; it is used as a source of sulphur in e.g. KLIGLER’S IRON AGAR. (See also RHODANESE.) thiosulphate–citrate–bile salts agar See TCBS AGAR. Thiothrix A genus of GLIDING BACTERIA (see CYTOPHAGALES); species occur e.g. attached to surfaces in sulphide-containing freshwater and marine habitats, particularly in flowing water, where dissolved oxygen levels are ca. 10% of the saturation value. The organisms are sheathed, non-gliding filaments which form gliding gonidia from the unattached end of the filament; filaments adhere to the substratum or form rosettes. Metabolism appears to be mixotrophic: in those strains examined, small amounts of simple carbon compounds are required, and energy

seems to be derived from the oxidation of sulphide or thiosulphate; sulphur is deposited intracellularly. One strain of Thiothrix has been found to contain carboxysome-like structures, suggesting that it may be autotrophic. [Review: ARM (1983) 37 354–359.] thiourea derivatives (as antimicrobial agents) Antimicrobial derivatives of thiourea, (NH2 )2 CS, include e.g. diphenylthiourea, (C6 H5 NH)2 CS, which has been used as an antimycobacterial agent, and the THIOSEMICARBAZONES. Thiovulum A genus of bacteria (Proteobacteria) found e.g. in marine habitats characterized by the simultaneous presence of sulphide and oxygen; the organisms obtain energy by oxidizing sulphide/sulphur, and typically form a whitish layer at the interface of sulphidogenic sediments and oxygenated water. Cells of the sole species, T. majus, are spherical, with a diameter reported to range from 5 to 25 µm; the (flagellate) organisms can reach speeds of ∼600 µm/second [Microbiology (1994) 140 3109–3116]. thiram (TMTD) TetramethylTHIURAM DISULPHIDE: (CH3 )2 .N.CS. S.S.CS.N.(CH3 )2 ; an ANTIFUNGAL AGENT which is also active against (mainly) Gram-positive bacteria. (cf. DMDC.) Thiram has been used as an antiseptic in the topical treatment of dermatophyte infections, and as an agricultural antifungal agent (e.g. as a seed dressing, and for the control of apple scab, Botrytis fruit rots, etc). Thiram (being insoluble in water) is used in aqueous suspensions. −35 sequence See PROMOTER. thistle mottle virus See CAULIMOVIRUSES. thiuram disulphides These compounds (R2 .N.CS.S.S.CS.N.R2 ) are formed by the mild oxidation of DITHIOCARBAMATES. See e.g. METIRAM and THIRAM. Thogoto virus An unclassified virus (see ORTHOMYXOVIRIDAE) which has been isolated from ticks and mammals; it has been implicated in a severe human disease (optic neuritis, meningoencephalitis) in Africa. Thoma chamber See COUNTING CHAMBER. thraustochytrids A category of eukaryotic organisms which are generally classified together with the LABYRINTHULAS (q.v.). (The thraustochytrids were formerly included within the Oomycetes – either as a family, Thraustochytriaceae, of the Saprolegniales, or as a distinct order, Thraustochytriales.) The organisms are widely distributed in marine and esturaine waters, living – apparently mainly as saprotrophs – on algae, plants, organic detritus, etc. The vegetative stage consists of a rounded or oval, somewhat amoeboid cell from which arise ectoplasmic filaments that branch and anastomose to form a rhizoid-like ectoplasmic net. The net is produced from sagenogenetosomes (sagenogens, ‘bothrosomes’) which are essentially similar to those of labyrinthulas; it appears to function in adhesion and nutrition (which is osmotrophic) and to some extent in motility, but the cell does not move into the net (cf. LABYRINTHULAS). The cell body serves as a sporangium which, in most species, gives rise to laterally biflagellate zoospores resembling those of LABYRINTHULAS (although apparently lacking an eyespot). Genera include Aplanochytrium (which produces aplanospores instead of zoospores), Japonochytrium, Labyrinthuloides, Schizochytrium and Thraustochytrium. Thraustochytrium See THRAUSTOCHYTRIDS. three-component regulatory system See BACTERIOCINS. three-for-one model (3-for-1 model) A model which describes the mode in which newly synthesized PEPTIDOGLYCAN (q.v.) is incorporated in the sacculus of a growing cell [Microbiology (1996) 142 1911–1918]. 773

three-micron DNA plasmid

long axis of the cell

(a)

(b)

(c) THREE-FOR-ONE MODEL: incorporation of newly synthesized peptidoglycan in the sacculus of a growing cell of Escherichia coli (simplified outline, diagrammatic). In PEPTIDOGLYCAN (q.v.), the glycan backbone chains are perpendicular to the long axis of the cell; the diagram shows an end-on view of backbone chains (open circles) joined by peptide bridges (straight lines). (a) A peptidoglycan monolayer; the monolayer is a stress-bearing structure and is under considerable tension. The chain in the centre ( ) – a ‘docking’ chain – is to be replaced by three chains (hence 3-for-1). (b) A triplet of three linked chains is located below (i.e. on the cytoplasmic side of) the peptidoglycan monolayer, with the flanking chains of the triplet covalently bound either side of the docking chain; in this particular plane, a stem peptide from each flanking chain has bound to the e-amino group of a dimeric peptide bridge to form a trimeric bridge (see legend to figure in entry PEPTIDOGLYCAN). (c) The docking chain has been removed by enzymic action, and – because of the tension in the monolayer – the incoming triplet of chains has taken up its position in the sacculus; note that this contributes to cell elongation. The model assumes that the central chain in the incoming triplet will, when incorporated in the sacculus, function as a new docking chain; for this reason, the dimeric bridge to each flanking chain is assumed to have a free e-amino group located in the stem peptide of the flanking chain. For cell length to double during the cell cycle, the model assumes that (i) docking and non-docking chains alternate in the sacculus, and (ii) only those docking chains which are present at the start of the new cell cycle will be replaced by an incoming triplet; that is, ‘new’ docking chains inserted during the current cell cycle will not be replaced until the next cell cycle. For this purpose, the growth mechanism must be able to distinguish ‘old’ from ‘new’ docking chains. This is possible because newly synthesized peptidoglycan is linked to the sacculus solely by tetra-tetra peptide bridges; it is therefore postulated that ‘new’ chains (identified by their tetra-tetra links) are not recognized as docking chains, but that, at the start of each new cell cycle, all tetra-tetra links will have been changed enzymically (by an LD-carboxypeptidase) to tetra-tri links, and that this allows recognition of the functional docking chains. Reproduced from Bacteria, 5th edition, Figure 3.1, page 42, Paul Singleton (1999) copyright John Wiley & Sons Ltd, UK (ISBN 0471–98880–4) with permission from the publisher.

An outline of the model is shown in the diagram. It is postulated that co-ordination of the synthetic and lytic aspects of the process involves enzymes that include PENICILLIN-BINDING PROTEINS and ‘lytic transglycosylases’ (enzymes that degrade a glycan strand processively). three-micron DNA plasmid (3µ plasmid; also 3µm plasmid) A cccDNA plasmid, of unknown biological role, found e.g. in strains of Saccharomyces cerevisiae and other yeasts; 3µ plasmids appear to be excised portions of chromosomal DNA – each corresponding to a unit of the host cell’s repetitive sequence of rRNA genes. [ARM (1983) 37 266.] (See also TWO-MICRON DNA PLASMID.) three-site model (of translation) See PROTEIN SYNTHESIS. threitol A 4-carbon POLYOL. D-Threitol occurs in certain fungi, e.g. Armillaria mellea. L-threonine biosynthesis See Appendix IV(d). threshold cycle (in quantitative PCR) See TAQMAN PROBES. -thrix A suffix signifying a hair or thread. thrombin See FIBRIN. thrombocytes Syn. PLATELETS. Thrombocytozoons ranarum An intracellular parasite of certain frogs (e.g. Rana septentrionalis, the mink frog) which occurs

exclusively in the thrombocytes of its host; T. ranarum is apparently a Gram-type-positive prokaryote. [J. Parasitol. (1984) 70 454–456.] thrombolite See STROMATOLITES. thrush See CANDIDIASIS. thujaplicins Isopropyltropolones, fungitoxic compounds formed by the Western Red Cedar (Thuja plicata); they appear to be responsible for the high resistance to fungal attack of timber from T. plicata. (See also TIMBER PRESERVATION.) thuringiensin (b-exotoxin) An exotoxin produced by Bacillus thuringiensis; it is apparently a specific inhibitor of DNAdependent RNA polymerase, acting as an ATP analogue. Thuringiensin is toxic to a wide range of insects and to some vertebrates; strains of B. thuringiensis used commercially for biological control (see DELTA-ENDOTOXIN) are therefore usually not thuringiensin-producers. thuringiolysin 0 See THIOL-ACTIVATED CYTOLYSINS. thylakoids Flattened, membranous vesicles which occur in the cytoplasm of nearly all CYANOBACTERIA (cf. GLOEOBACTER) and in the CHLOROPLASTS of ALGAE and higher plants; thylakoid 774

timber spoilage membranes contain the CHLOROPHYLLS and electron carriers etc involved in PHOTOSYNTHESIS. In cyanobacteria, thylakoids typically occur near, and parallel to, the cell envelope, but seem to be structurally distinct from the cytoplasmic membrane; unlike the thylakoids in higher plants and some algae, those in cyanobacteria are not stacked (cf. PROCHLOROPHYTES). (See also PHYCOBILIPROTEINS.) In at least some cyanobacteria, thylakoid membranes are the sites of respiratory (as well as photosynthetic) electron transport; during photosynthetic or respiratory activity protons are pumped into the thylakoid vesicles – generating a proton motive force (see CHEMIOSMOSIS) across the thylakoid membrane [Book ref. 75, pp. 199–218]. Algal chloroplasts may contain individual (unassociated) thylakoids (in the Rhodophyta); longitudinally-adjacent pairs of thylakoids (in the cryptophytes); bands of three thylakoids (in the chrysophytes, diatoms, dinoflagellates, euglenoid flagellates, and members of the Phaeophyta, Prymnesiophyceae and Xanthophyceae); or bands of 2–6 thylakoids (Chlorophyta). A stack of ca. four or more thylakoids is termed a granum. thylaxoviruses Viruses of the ONCOVIRINAE. thymic aplasia (congenital) Syn. DIGEORGE SYNDROME. thymidine See NUCLEOSIDE and Appendix V(b). (See also double thymidine blockade in SYNCHRONOUS CULTURE.) thymidine kinase (TK; ATP:thymidine 5′ -phosphotransferase; EC 2.7.1.21) An enzyme which catalyses the phosphorylation of thymidine to thymidine 5′ -monophosphate; it is an important enzyme in the pyrimidine salvage pathway. TKs occur in various bacteria [JGM (1985) 131 3091–3098] and in eukaryotic cells (in the cytoplasm and mitochondria), and are encoded by many DNA viruses [review: MS (1985) 2 369–375]. (See also e.g. ACYCLOVIR and HYBRIDOMA.) thymine dimer See ULTRAVIOLET RADIATION. thymocyte An immature T cell undergoing development in the thymus gland. thymol See PHENOLS. thymol blue A PH INDICATOR. Acid range: pH 1.2–2.8 (red to yellow); pKa1 1.5. Alkaline range: pH 8.0–9.6 (yellow to blue); pKa2 8.9. thymolphthalein A PH INDICATOR: pH 9.3–10.5 (colourless to blue); pKa 9.9. thymus-dependent antigen (TD antigen; T-dependent antigen) Any antigen (e.g. most soluble proteins) which can trigger ANTIBODY FORMATION in antigen-specific B LYMPHOCYTES only with the help of T LYMPHOCYTES. (TD antigens do not elicit antibody in congenitally athymic individuals.) thymus-independent antigen (TI antigen; T-independent antigen) Any antigen which can trigger ANTIBODY FORMATION in antigenspecific B LYMPHOCYTES without help from T LYMPHOCYTES. TI antigens include e.g. lipopolysaccharides, polymerized flagellin, dextrans and levans. (See also POLYCLONAL ACTIVATOR.) TI antigen THYMUS-INDEPENDENT ANTIGEN. Ti plasmid See CROWN GALL. tiamulin A semisynthetic antibiotic which inhibits PROTEIN SYNTHESIS in bacteria but which has little or no effect against archaeans. It apparently interacts with the 50S subunit of the ribosome, inhibiting the peptidyltransferase reaction. ticarcillin See PENICILLINS. tick-borne encephalitis virus See FLAVIVIRIDAE. Tilletia A genus of plant-parasitic fungi (order USTILAGINALES) which typically attack the ovaries of the host plant, though the leaves may also be parasitized; Tilletia spp are the causal agents of e.g. COMMON BUNT and dwarf bunt.

In a typical life cycle, a teliospore germinates to give rise to an elongated, aseptate or uniseptate structure bearing an apical tuft of eight or more thread-like basidiospores (sometimes called ‘primary sporidia’ or ‘primary conidia’); in e.g. T. caries (which exhibits HETEROTHALLISM) the basidiospores on a given structure are of two different mating types. While still attached, the basidiospores conjugate in pairs, giving rise to H-shaped forms within which plasmogamy occurs; subsequently, each (detached) H-shaped binucleate form, or mycelium derived from it, gives rise to binucleate ballistoconidia (sometimes called ‘secondary sporidia’ or ‘secondary conidia’). The conidia germinate to form dikaryotic hyphae which initiate infection of a fresh host and subsequently give rise to teliospores. Tilletiaceae See USTILAGINALES. tilmicosin A MACROLIDE ANTIBIOTIC which has been used e.g. against Mycoplasma bovis in the treatment of CALF PNEUMONIA; in vitro tests on field isolates of M. bovis indicate that significant levels of resistance have developed against tilmicosin [VR (2000) 146 745–747]. Tilopteris See PHAEOPHYTA. tilorone (2,7-bis-[2-(diethylamino)ethoxyl]-9-fluorenone) An antiviral, antitumour agent which seems to (a) induce INTERFERON synthesis, and (b) interfere directly with virus expression by functioning as an INTERCALATING AGENT (f ca. 13° ) with a preference for AT-rich regions of dsDNA. Tilsit cheese See CHEESE-MAKING. Tilt See PROPICONAZOLE. timber decay See TIMBER SPOILAGE and TREE DISEASES. timber preservation The seasoning (i.e. drying) of timber renders it less susceptible to fungal attack (see TIMBER SPOILAGE), and may facilitate penetration by chemical preservatives; once dried, timber can be preserved by e.g. preventing the access of air and moisture by the use of sealants or paint films (see also PAINT SPOILAGE). In some cases (e.g. elm wood) decay can be inhibited by waterlogging which limits the supply of oxygen to potential spoilage fungi. Decay of timber may also be prevented or delayed by the use of PRESERVATIVES – e.g. CREOSOTE, sodium fluoride, pentachlorophenol, borates (alone or with QACs), copper naphthenate, and tributyl tin oxide (alone or with QACs). Most of these substances are inherently fungitoxic, but tributyl tin oxide (TBTO) inhibits fungal attack by binding strongly to cellulose, rendering it insusceptible to fungal CELLULASES; wood treated with TBTO may still be susceptible to lignin-utilizing WHITE ROT fungi unless TBTO is used in conjunction with e.g. a phenolic preservative to protect the lignin. The control of SOFT ROT can be achieved only by the use of preservatives which penetrate into the cell walls of the wood. Preservatives may be applied either as surface coatings or by the use of specialized procedures (see e.g. BETHELL PROCESS; BOUCHERIE PROCESS; SAUG–KAPPE PROCESS). Aqueous preservatives may be retained in treated timbers e.g. by the formation of insoluble precipitates; the insolubility of some preservatives prevents leaching under damp or wet conditions. (Certain types of wood contain natural fungitoxic substances – e.g. PINOSYLVIN in pine, TANNINS in oak, THUJAPLICINS in Western Red Cedar.) (See also HETEROBASIDION.) Decay of chemically treated timber may occur e.g. through splitting – which permits fungal penetration through a treated zone. Rhizomorphs may enable a fungus to cross treated (or nonnutrient) zones (see e.g. DRY ROT), while some fungi can detoxify copper preservatives by converting them to copper oxalate. timber spoilage Microbial spoilage of timber is caused primarily by fungi – particularly basidiomycetes – and involves decay 775

timber staining tinsel flagellum See FLAGELLUM (b). tintinnid See TINTINNINA. Tintinnidium See TINTINNINA. Tintinnina (‘tintinnids’) A suborder of ciliate protozoa (order OLIGOTRICHIDA); most species are marine pelagic organisms, but some occur in freshwater habitats. Cells: cylindrical, conical or vase-shaped, typically one hundred to several hundred micrometres in length; all are loricate and highly contractile. Somatic ciliature is reduced, but oral ciliature is conspicuous and includes a closed ring of cilia around the apical oral region. A perilemma is commonly or always present, and in some cases the lorica is covered by small inorganic particles. Genera include e.g. Codonella, Salpingella, Tintinnidium, Tintinnopsis, and Tintinnus. [Grazing, respiration, excretion and growth rates of tintinnids: Limn. Ocean. (1985) 30 1268–1282.] Tintinnopsis See TINTINNINA. Tintinnus See TINTINNINA. tioconazole An AZOLE ANTIFUNGAL AGENT. [Review of antimicrobial activity and therapeutic use in superficial mycoses: Drugs (1986) 31 29–51.] TIP (1) THERMAL INACTIVATION POINT. (2) Tumour-inducing principle: the Ti plasmid responsible for CROWN GALL formation. Tipula iridescent virus See IRIDOVIRUS. tir gene See PATHOGENICITY ISLAND. tirandamycin An antibiotic which appears to be structurally and functionally similar to STREPTOLYDIGIN. Tissierella A proposed genus of bacteria which includes organisms currently classified as Bacteroides praeacutus (proposed new name: T. praeacuta) [IJSB (1986) 36 461–463]. tissue culture (1) The in vitro culture (growth) or maintenance of isolated mammalian (or other) tissues or organs, or of populations of individual cells obtained by disruption of such tissues. Those procedures which involve populations of individual cells are also referred to as cell culture; the following account refers specifically to cell culture. Cell cultures (TISSUE CULTURE sense 2) are widely used e.g. for the culture of viruses, and for studies in cancer research, immunology, toxicology etc; they are also used to culture certain bacteria (e.g. species of Chlamydia and Rickettsia). Cell cultures are prepared and handled with an ASPETIC TECHNIQUE. Culture vessels include LEIGHTON TUBES, medical flats, roller bottles (see ROLLER CULTURE), Roux flasks, test-tubes etc; vessels may be made of (neutral-pH) glass (e.g. borosilicate or flint glass) or of certain plastics (e.g. polystyrene). Media. A growth medium permits cellular growth and division; it consists essentially of a BALANCED SALT SOLUTION supplemented with e.g. glucose and/or peptone, various amino acids and vitamins, a pH indicator (e.g. PHENOL RED), a buffer system (often bicarbonate or HEPES), antibiotic(s), and (usually) 5–10% calf serum. (Serum-less media are also used.) Antibiotics are included to prevent the development of microbial contaminants which may be present; however, the continual suppression of contaminants during SERIAL PASSAGE is undesirable, and periodic subcultures should be made in antibiotic-free media in order to detect contaminants. Common bacterial contaminants include species of Acholeplasma and Mycoplasma (PCR-based detection e.g. with Mycoplasma Plus PCR Primer Set from Stratagene). Common growth media include various modifications of EAGLE’S MEDIUM – e.g. basal medium Eagle (BME), and minimal essential medium (MEM) – and medium 199. A maintenance medium is used to preserve the viability and properties of a population of cells while restricting to a minimum their growth and division; growth media containing lower levels of serum (e.g. 1%) are often used as maintenance media.

(see e.g. BROWN ROT, DRY ROT, POCKET ROT, SOFT ROT, WET and WHITE ROT) and/or staining (see TIMBER STAINING). Commonly, only wood having a moisture content greater than ca. 20% is susceptible to fungal attack (cf. DRY ROT); the moisture content is calculated as the weight of water in a sample of timber divided by the dry weight of that sample. In fallen or freshly felled timber the sapwood is particularly vulnerable to SAP-STAIN and early decay by any of a range of fungi; thus e.g. fallen birch branches rapidly succumb to a brown cubical rot (caused by e.g. Piptoporus betulinus) or to a soft white fibrous rot (caused e.g. by Heterobasidion annosum – see HETEROBASIDION). Timber may also support a surface growth of non-cellulolytic, non-lignolytic ascomycetes and deuteromycetes (cf. SOFT ROT (1)); such growth generally causes little or no damage to the timber. Fungi of importance in the decay of domestic and industrial timbers include e.g. Serpula lacrymans (see DRY ROT) and Coniophora puteana (see WET ROT); Lentinus lepideus is moderately resistant to creosote and can cause a brown rot in e.g. railway sleepers. (See also PAPER SPOILAGE; TIMBER PRESERVATION; TREE DISEASES.) timber staining (by fungi) Various wood-infecting fungi cause discoloration in felled timber and in standing trees; some infections are superficial, but in others the fungus grows into the timber or is carried in by wood-boring beetles. Superficial staining can be caused by a range of fungi (e.g. species of Alternaria, Fusarium, Penicillium) and typically does not affect the strength or value of the timber; deep staining may weaken the timber (see e.g. BROWN OAK). Staining may be due to the production of a fungal pigment or to an optical effect (see BLUESTAIN). (See also GREEN OAK; TIMBER PRESERVATION.) Timentin A composite antibiotic consisting of ticarcillin (see PENICILLINS) and CLAVULANIC ACID. [Clinical evaluation: Am. J. Med. (1985) 79 Supplement 5B 1–196; laboratory and clinical perspective: JAC (1986) 17 Supplement C 1–244.] (cf. AUGMENTIN.) timothy-grass bacillus Mycobacterium phlei. tin (as an antimicrobial agent) Tin is a HEAVY METAL which, in elemental or compound form, can exert antimicrobial activity. The presence of metallic tin has been reported to inhibit growth and toxin production by Clostridium botulinum in food contained in tin-plate cans [cited in Book ref. 35, p. 282]. (If the inside of a can is significantly de-tinned – e.g. by CURING salts, or by certain acidic fruits – the underlying steel may rapidly corrode and give rise to a HYDROGEN SWELL.) Organotins (i.e. tin-containing organic compounds) are typically more active than inorganic compounds of tin – trialkyltins (e.g. TBTO) being among the most effective. (See also FENTIN.) Trisubstituted organotins exhibit microbistatic activity at low concentrations – apparently by inhibiting ATP synthesis; at high concentrations they can be microbicidal, possibly by disrupting the cytoplasmic membrane. tinangaja disease A disease of coconut palms which occurs on the island of Guam; it is apparently caused by the COCONUT CADANG-CADANG VIROID. tincture of iodine See IODINE (a). tinder fungus Fomes fomentarius. tinea See RINGWORM. (See also e.g. FAVUS; PITYRIASIS NIGRA; PITYRIASIS VERSICOLOR.) tinidazole See NITROIMIDAZOLES. Tinopal AN A FLUORESCENT BRIGHTENER used e.g. as a selective antibacterial agent; in e.g. Escherichia coli it apparently inhibits RNA polymerase [JGM (1984) 130 1999–2005]. [Use for distinguishing phytopathogenic from saprotrophic Pseudomonas spp: JAB (1985) 58 283–292.] ROT,

776

TMA titer See TITRE. titration (mol. biol.) Concentration-dependent interaction between a regulatory molecule and other molecule(s) or specific nucleotide sequence(s) by means of which the level of activity of the regulatory molecule is controlled. (See e.g. F PLASMID (replication).) titre (titer) (serol., virol.) A numerical expression for the ‘concentration’ of specific antibodies, antigens, virions etc in a given sample. If the titre of antibodies or antigens is determined by an END-POINT TITRATION, the titre is equal, numerically, to the dilution factor of the highest dilution of sample giving a positive serological reaction. For example, if the end-point reaction mixture consisted of a 1/200 dilution of serum (antibody) and an equal volume of antigen, the titre of antibody can be given as 200 (‘initial serum dilution’) or 400 (‘final serum dilution’); these titres may, alternatively, be quoted as 1/200 and 1/400, respectively. Virus titres may be determined e.g. by the PLAQUE ASSAY method (see also END-POINT DILUTION ASSAY). TK THYMIDINE KINASE. TLC Thin-layer CHROMATOGRAPHY. Tm (Tm ) See THERMAL MELTING PROFILE. TMA Trimethylamine (see e.g. FISH SPOILAGE). TMA (transcription-mediated amplification) A method used for the isothermal amplification of RNA target sequences; the principle of TMA is the same as that of NASBA (q.v.) – one practical difference being that, in the commercial applications of TMA, use is made of the RNase H activity of reverse transcriptase, so that only two enzymes are used. Commercial TMA- and NASBA-based tests differ also in the way in which amplified target sequences are detected. In TMA-based tests, the targets are detected by a so-called hybridization protection assay (HPA). HPA involves the use of DNA probes labelled with acridinium ester. After allowing time for probe–target hybridization, an added reagent hydrolyses the acridinium ester label on all unbound probes – the label on bound probes being protected as a consequence of its location within the probe–target duplex; subsequent addition of other reagents elicits CHEMILUMINESCENCE from the bound probes – emitted light being measured by a luminometer in relative light units (RLUs). Commercial applications of TMA include several diagnostic tests – one of which, the amplified Mycobacterium tuberculosis direct test (AMTDT; Gen-Probe, San Diego, USA), was approved by the U.S. Food & Drug Administration (FDA) for detection of Mycobacterium tuberculosis in (smear-positive) respiratory specimens (e.g. sputa). A new-format ‘enhanced’ AMTDT, which uses a larger volume of sample, was approved by the FDA in 1998. A TMA-based test for Chlamydia trachomatis in urogenital specimens was approved by the FDA in 1996; the principle of this test (AMP CT) is identical to that of the AMTDT. [Evaluation of AMP CT for the detection of Chlamydia trachomatis in a high-risk population of women: JCM (1997) 35 676–678. Evaluation of AMTDT for non-respiratory specimens: JCM (1997) 35 307–310. Comparison of original and ‘enhanced’ versions of AMTDT for respiratory and non-respiratory specimens: JCM (1998) 36 684–689. Evaluation of ‘enhanced’ AMTDT for rapid diagnosis of pulmonary tuberculosis in a high-risk prison population: JCM (1999) 37 1419–1425. False-positive results with AMTDT in patients with Mycobacterium avium and M. kansasii infections: JCM (1999) 37 175–178.]

In monolayer culture a population of cells is incubated in a shallow layer of growth medium until the cells form a more or less confluent layer, one cell thick, on the inner surface of the culture vessel; macroscopically, the monolayer appears as a translucent film. The initial cell suspension may be derived from fresh tissue (see PRIMARY CULTURE) or from an ESTABLISHED CELL LINE. Preparation of a monolayer culture from fresh tissue. Selected tissue is cut into small pieces and washed several times with prewarmed (30–37° C) phosphate-buffered saline (PBS). The tissue is then subjected to trypsinization, i.e., digested in PBS containing trypsin (see PROTEASES) (0.05–0.1% w/v) – the whole being kept at 30–37° C and stirred mechanically for 20–30 min. (Trypsin weakens the intercellular bonds; excessive trypsinization can damage cells.) The turbid supernatant (containing damaged cells) is discarded, and the tissue fragments are again digested in fresh PBS–trypsin. The supernatant, containing single cells and small aggregates, is centrifuged (ca. 150–200 g/5 min) and the pellet of cells is resuspended in fresh growth medium. The concentration of viable cells is determined (see COUNTING CHAMBER and VITAL STAINING) and is adjusted (by diluting with growth medium) to ca. 105 cells/ml. A small volume of the suspension is then incubated (37° C for mammalian cells) for several days, or a week or more, until a monolayer develops on the inner surface of the culture vessel; for flat-surfaced culture vessels (e.g. medical flats, Roux flasks) ca. 15–20 ml of cell suspension is required for an area of 100 cm2 . (Test-tubes or bottles of circular cross-section are used for ROLLER CULTURE.) When cultured, animal cells generally become either spindleshaped (‘fibroblast-like’) or polygonal (‘epithelioid’). For SERIAL PASSAGE, the cells are first stripped, i.e. detached from the surface on which they have been grown: the monolayer is subjected for 1–2 min to a stripping agent – e.g. PBS containing VERSENE (ca. 0.02–0.05%) and ca. 0.1% trypsin; the stripping agent is decanted, and the detached, disaggregated cells are washed and resuspended in fresh growth medium, and can be used to prepare fresh cultures. Cells, in ampoules, can be preserved for long periods e.g. by FREEZING. Transformation. After a certain number of serial passages, cells may die out or may develop into an ESTABLISHED CELL LINE. In the latter case the cells undergo certain alterations (usually termed transformation) such that they exhibit some or all of the properties characteristic of tumour cells: an apparent capacity for unlimited in vitro growth and division; the ability to grow in soft agar; the development of new surface antigens; the ability to form tumours when injected into animals; an increase in the rate of nutrient uptake; a loss of contact inhibition (i.e. inhibition of movement and cell division due to contact with neighbouring cells). (Loss of contact inhibition in a monolayer culture permits the development of multilayer colonies from the clones of transformed cells.) These changes may also be brought about by certain viruses, e.g. SV40 and Rous sarcoma virus. The characteristics of cultured cells may be monitored e.g. by serological means or by examining the KARYOTYPE of the (COLCHICINE-treated) cells. (2) Any population of cells involved in tissue culture (sense 1). (See also HYBRIDOMA and SYNCHRONOUS CULTURE.) tissue cyst (of coccidia) See e.g. TOXOPLASMOSIS. tissue-destructive factor See LEGIONELLOSIS. tissue factor (TF) See DISSEMINATED INTRAVASCULAR COAGULATION. tissue factor pathway inhibitor (TFPI) See DISSEMINATED INTRAVASCULAR COAGULATION. 777

TMAO [Isothermal nucleic-acid-amplification methods (TMA, NASBA, SDA): Book ref. 221, pp 126–151.] TMAO Trimethylamine-N-oxide (see e.g. FISH SPOILAGE). TMEV THEILER’S MURINE ENCEPHALOMYELITIS VIRUS. TMPD Tetramethyl-p-phenylenediamine: a reagent which can e.g. reduce cytochrome oxidase (see ELECTRON TRANSPORT CHAIN); oxidized TMPD can be reduced by ascorbic acid. (See also KOVACS’ OXIDASE REAGENT.) TMS Tetramethylsilane (see NUCLEAR MAGNETIC RESONANCE). TMTD See THIRAM. TMV TOBACCO MOSAIC VIRUS. Tn1 See Tn3. Tn2 See Tn3. Tn3 A 4957-bp class II TRANSPOSON which has identical 38-bp terminal inverted repeats and carries a gene (bla) for a TEMtype b-LACTAMASE; Tn3 occurs e.g. in plasmid R1drd-19. Tn3 insertion tends to occur preferentially at target sites in AT-rich regions of DNA, and results in a 5-bp duplication of target DNA. Two Tn3 genes (tnpA and tnpR) are necessary for transposition, which occurs by a two-stage mechanism via a COINTEGRATE intermediate. The tnpA gene specifies a transposase responsible (at least in part) for the formation of a cointegrate. The tnpR gene specifies a resolvase which can catalyse resolution of the cointegrate by SITE-SPECIFIC RECOMBINATION involving a region – termed IRS (internal resolution site) – between the tnpA and tnpR genes in each Tn3 copy. Tn3 resolvase acts specifically on a replicon containing two IRS regions in the same orientation, and cannot act on IRS regions in different replicons; the resolution reaction is therefore irreversible. [Model for Tn3 resolvase action: Cell (1985) 40 147–158.] (Tn3 cointegrate intermediates can also be resolved by general recombination involving the host recA system.) The tnpR resolvase also regulates the frequency of Tn3 transposition by acting as a repressor and preventing expression of both tnpA and tnpR genes. Many bacterial TRANSPOSABLE ELEMENTS are closely related to Tn3 : all have related short (35–40 bp) inverted repeats, all induce a 5-bp duplication in target DNA on insertion, all are transposed by a two-stage mechanism involving the formation and resolution of a cointegrate, and most show TRANSPOSITION IMMUNITY. Tn3-like elements include e.g. Tn1 and Tn2 (both ca. 5 kb, encoding TEM-like b-lactamase), Tn4 (encoding resistance to ampicillin, streptomycin and sulphonamides), Tn21 (q.v.), Tn501 (q.v.), Tn551 (5.3 kb, encoding resistance to erythromycin, derived from a Staphylococcus aureus plasmid), Tn1721 (q.v.), Tn2603 (22 kb, encoding an OXA-1 b-lactamase and resistance to streptomycin, sulphonamides and mercury – cf. Tn2410), and gd (= IS1000, a 5.8-kb INSERTION SEQUENCE which shares extensive DNA homology with Tn3 ). Tn3 and the Tn3like elements are sometimes collectively termed TnA. Two subgroups of ‘TnA’ elements are recognized e.g. on the basis of whether the tnpA and tnpR genes are transcribed in opposite directions (as in Tn3 and gd) or in the same direction (as in Tn4, Tn21, Tn501, Tn1721, Tn2603 ). [Review of Tn3 and related transposons: Book ref. 20, pp. 223–260.] Tn4 See Tn3. Tn5 A 5818-bp composite TRANSPOSON containing three antibiotic-resistance genes, one of which encodes aminoglycoside 3′ -phosphotransferase (conferring resistance to kanamycin and other aminoglycoside antibiotics). The three, contiguous antibiotic-resistance genes are flanked by a pair of terminal inverted repeats: two IS50 insertion sequences (IS50 L

and IS50 R) that differ slightly from one another. Each IS50 sequence is flanked by a pair of 19-bp sequences referred to as the outer end (OE) and inner end (IE); the two OE sequences thus form the two ends of the transposon. IS50 R encodes two proteins: P1 (a cis-acting transposase, Tnp) and P2 (an inhibitor of the transposase, Inh) – P2 being encoded by the same reading frame as P1 but lacking the Nterminal 55 amino acids. (IS50 L encodes two corresponding proteins, P3 and P4; however, IS50 L contains an ochre codon so that P3 and P4 are non-functional proteins.) Tnp can catalyse transposition of (i) the entire transposon (Tn5 ) or (ii) IS50 ; transposition of Tn5 involves the two OE sites, whereas transposition of IS50 involves one OE site and one IE site. Tnp is characterized by a low level of activity which is further down-regulated by Inh; the relative levels of Tnp and Inh influence the frequency of transposition. In vivo, host factors tend to favour transposition from the OE sites (in preference to the IE sites). Other regulatory factors in vivo include dam methylation (see DAM GENE) which negatively affects the function of the P1 promoter (and also results e.g. in coupling transposition to DNA replication). [Tn5 (review): ARM (1993) 47 945–963.] Early studies suggested that transposition of Tn5 may involve a cut-and-paste (rather than a replicative) mechanism (see TRANSPOSABLE ELEMENT) [CSHSQB (1984) 49 215–226], but subsequent work suggested the involvement of cointegrates (i.e. a replicative mechanism) [JMB (1986) 191 75–84]. However, more recent evidence favours a cut-and-paste model [JBC (1998) 273 7367–7374]. The latter study [JBC (1998) 273 7367–7374] demonstrated that transposition could be achieved in an in vitro system consisting of: (i) transposase, (ii) DNA flanked by OE sequences, and (iii) target DNA. Such in vitro transposition is optimized by a ‘hyperactive’ form of transposase transcribed from IS50 R containing three mutations – one of which blocks transcription of the inhibitor (Inh) while another enhances the binding of transposase to OE sequences. Tn7 A TRANSPOSON which can insert into the chromosome of Escherichia coli with a high degree of target specificity; the target site is designated attTn7. Insertion of Tn7 involves several Tn7-encoded proteins: TnsA, TnsB, TnsC and TnsD; TnsA and TnsB jointly provide transposase activity. Initially, TnsD binds to attTn7 in a sequence-specific way, and such binding distorts the 5′ end of the binding site; it has been suggested that this distortion of DNA acts as a signal for the recruitment of TnsC to the site [EMBO (2001) 20 924–932]. A second, distinct pathway of transposition of Tn7 involves the transposon-encoded TnsA, TnsB, TnsC and TnsE; TnsE, which binds DNA in a structure-dependent way, promotes insertion of Tn7 into (i) certain plasmids, and (ii) the chromosome of E. coli at sites proximal to double-stranded breaks in DNA and also at locations where DNA replication terminates [GD (2001) 15 737–747]. Tn9 A 2638-bp composite TRANSPOSON which includes terminal, directly repeated IS1 elements and a gene (cat) for resistance to CHLORAMPHENICOL (cat encodes chloramphenicol acetyltransferase – an enzyme which also inactivates fusidic acid). Tn9 apparently transposes by a replicative process involving cointegrate formation, recA function being necessary for cointegrate resolution [JMB (1986) 191 75–84]. (cf. Tn3 and Tn5.) Tn9 occurs e.g. in the R plasmid pSM14 (= R14), a plasmid which also contains Tn10. Tn9-derived chloramphenicol resistance from Gram-negative bacteria can be cloned in, but not 778

TNF phenotypically expressed in, Bacillus subtilis [PNAS (1982) 79 5886–5890]. (See also IS1.) Tn10 A 9.3-kb composite TRANSPOSON which carries a gene for tetracycline resistance; Tn10 occurs e.g. in the transmissible plasmid R100 (= R222). The mechanism of Tn10 transposition is distinct from that of Tn3 (q.v.); it apparently involves a nonreplicative ‘cut-and-paste’ mechanism in which excision of the transposon from the donor molecule (by double-stranded breaks at each end) is followed by insertion of the transposon into the new target site. The remainder of the donor molecule is probably lost (‘donor-suicide’ model). [Genetic evidence for non-replicative Tn10 transposition: Cell (1986) 45 801–815.] The two ends of Tn10 are IS elements (IS10, 1.4 kb) in opposite orientation; the two IS10 elements are similar but not identical, and are designated IS10-Right (IS10-R) and IS10Left (IS10-L). IS10-R encodes at least one protein (transposase) which acts at the ends of Tn10 and is necessary for its transposition; the transposase is apparently preferentially cisacting, possibly migrating along the DNA molecule rather than being freely diffusible in the cell cytoplasm. IS10-R can promote normal levels of transposition (e.g. ca. 10−7 transpositions/TE/bacterial generation) even when IS10-L is inactive; however, IS10-L is functionally defective and can provide only ca. 1–10% of the transpositional activity of IS10-R. Insertion of Tn10 into a new target site – presumably recognized by the IS10-R transposase – results in the duplication of a 9-bp target sequence. The preferred (‘hot-spot’) target site for Tn10 contains a symmetrical 6-bp sequence within the 9-bp sequence (NGCTNAGCN) duplicated during insertion; insertion can also occur, less efficiently, at many other sites, with concomitant duplication of a different 9-bp sequence. (See also DAM GENE and MULTICOPY INHIBITION.) Tn21 A 19.3-kb Tn3-like transposon (see Tn3) present e.g. in plasmid R100 from Shigella flexneri ; it encodes resistance to sulphonamides, streptomycin and mercuric ions. Tn21 transposition is regulated by a modulator protein encoded by a gene (tnpM) located upstream of the Tn21 IRS. The tnpA, tnpR and tnpM genes are all transcribed in the same direction (cf. Tn3). The Tn21 modulator apparently enhances Tn21 transposition and suppresses cointegrate resolution by Tn21 resolvase. A sequence homologous to the Tn21 tnpM gene has been observed in an analogous site in Tn501. [Cell (1985) 42 629–638.] Tn501 An 8.2-kb Tn3-like transposon (see Tn3) from Pseudomonas spp (plasmid pUS1); it encodes resistance to mercury. The frequency of transposition and efficiency of cointegrate resolution are both substantially increased in the presence of low levels of mercury, suggesting that the tnpA and tnpR genes can be transcribed from the same promoter as the inducible gene for mercury resistance. Tn501 may encode a modulator protein similar to that of Tn21 (q.v.). Tn501 provides ‘hot-spots’ for Tn3 insertion. Tn551 See Tn3. Tn554 A site-specific, repressor-controlled TRANSPOSON from Staphylococcus aureus; it carries (inducible) genes for resistance to erythromycin and spectinomycin. Tn916 See CONJUGATIVE TRANSPOSITION. Tn925 See CONJUGATIVE TRANSPOSITION. Tn951 A defective transposon of the Tn3 group (see Tn3) which encodes genes for lactose metabolism (lacZ and lacY); its ends are perfect inverted repeats (40 bp), but it apparently lacks genes for its transposition – transposition requiring Tn3-encoded transposase and resolvase. (cf. IS101.) Tn951 contains an IS1 sequence [MGG (1980) 178 367–374].

Tn1000 Syn. gd (see Tn3). Tn1207.1 See MACROLIDE ANTIBIOTICS. Tn1545 See CONJUGATIVE TRANSPOSITION. Tn1681 A TRANSPOSON which carries a gene for the heat-stable enterotoxin STa of enterotoxigenic Escherichia coli (see ETEC); Tn1681 contains two copies of IS1 in inverted orientation. Tn1721 An 11.4-kb Tn3-like transposon (see Tn3) encoding resistance to tetracycline. In the presence of tetracycline the resistance gene is duplicated many times, resulting in increased levels of tetracycline resistance. Tn2410 An 18.5-kb (probably Tn3-like) TRANSPOSON derived from plasmid R1767 from Salmonella typhimurium; it carries genes encoding an OXA-2 b-LACTAMASE and resistance to sulphonamides and mercury [JGM (1983) 129 2951–2957]. Tn2603 See Tn3. Tn3701 See CONJUGATIVE TRANSPOSITION. Tn5253 See CONJUGATIVE TRANSPOSITION. Tn5397 A conjugative transposon (see CONJUGATIVE TRANSPOSITION) which is found e.g. in Clostridium difficile (and which is transferable to e.g. Bacillus subtilis); it encodes resistance to tetracycline. Although related to Tn916, Tn5397 encodes a dual-function protein, TndX, that mediates both insertion and excision (in contrast to the products of the int and xis genes of Tn916 ). Tn5397 contains a group II intron which has been shown to undergo splicing in vivo [JB (2001) 183 1296–1299]. TnA See Tn3. tna operon An OPERON which includes the structural gene (tnaA) for TRYPTOPHANASE; tnaA is separated from the tna promoter by a long LEADER (tnaL) which contains several rho-dependent terminators [JB (1986) 166 217–223] (see TRANSCRIPTION) and a sequence (tnaC) encoding a 24-amino-acid leader peptide. The operon is subject to CATABOLITE REPRESSION and is inducible by tryptophan; translation of tnaC apparently plays an essential role in operon expression [JB (1986) 167 383–386]. In the absence of tryptophan, rho-dependent transcription termination occurs in the tnaL region, preventing expression of tnaA; however, in the presence of tryptophan, termination is prevented (see ANTITERMINATION), allowing tnaA gene expression. (cf. OPERON (attenuator control).) TNase Thermonuclease (see DEOXYRIBONUCLEASE). TNF Tumour necrosis factor: a pro-inflammatory cytokine (see CYTOKINES) synthesized by many types of cell on appropriate stimulation. The two forms of TNF, TNF-a and TNF-b, are both encoded by three-intron, single-copy genes. TNF-a (formerly ‘cachectin’) is produced e.g. by activated macrophages, by the Th1 subset of T lymphocytes, and by endothelial cells and leukocytes stimulated by lipopolysaccharides (see also CD14). TNF-a appears to have a wide range of activities which include (i) induction of APOPTOSIS in target cells, (ii) cytolysis of certain types of tumour, (iii) regulation of proliferation and differentiation in lymphocytes, (iv) upregulation of CELL ADHESION MOLECULES (E-selectins, ICAM-1) on endothelial cells during INFLAMMATION, (v) promotion of ADCC activity in neutrophils, (vi) stimulation of monocytes and macrophages to synthesize e.g. TNF-a, IL-1 and IL-6, and (vii) induction of certain CHEMOKINES (e.g. IL-8). Injection of TNF into animals gives rise to a syndrome indistinguishable from ENDOTOXIC SHOCK. In vitro studies suggest that TNF-a may upregulate endothelial toxin receptors during EHEC infection and (thus) promote the vascular damage associated with HAEMOLYTIC URAEMIC SYNDROME 779

tnpA gene TMV infects tobacco (Nicotiana tabacum) and other plants. The common, ‘Vulgare’ or field strain (U1 strain) usually causes a systemic disease of tobacco in which leaves are distorted, blistered, and marked with a mosaic of light and dark green patches; intracellular crystalline arrays of virus particles are commonly visible by light microscopy. Other TMV strains may affect other plants (e.g. strain Cc affects legumes, TMV-L affects tomatoes). (See also PATHOGENESIS-RELATED PROTEINS.) TMV is transmitted mechanically; it may remain infective for a year or more in soil or dried leaf tissue. The virions may be inactivated e.g. at pH 8 or by formaldehyde, iodine, etc; TIP: ca. 95° C. Preparations of TMV may be obtained from plant tissues e.g. by (NH4 )2 SO4 precipitation followed by differential centrifugation. The TMV ssRNA genome is ca. 6400 nucleotides long [sequence: PNAS (1982) 79 5818–5822] and is capped at the ′ ′ 5′ end (sequence: m7 G5 ppp5 Gp) but is not polyadenylated. The genomic RNA can serve as mRNA for a protein of MWt ca. 130000 (130 K) and another, produced by readthrough, of MWt ca. 180000 (180 K); however, it cannot function as messenger for the synthesis of e.g. coat protein. Other genes are expressed during infection by the formation of monocistronic, 3′ coterminal SUBGENOMIC MRNAS, including one (LMC) encoding the 17.5 K coat protein and another (I2 ) encoding a 30 K protein. (Other putative subgenomic mRNAs may be artefacts generated during electrophoresis [Book ref. 80, pp. 69–72].) The 30 K protein has been detected in infected protoplasts [Virol. (1984) 132 71–78]; it may be involved in the cell-to-cell transport of the virus in an infected plant. The functions of the two large proteins are unknown. Several dsRNA molecules – including dsRNAs corresponding to the genomic, I2 and LMC RNAs – have been detected in plant tissues infected with TMV; these are presumably intermediates in genome replication and/or mRNA synthesis – processes which appear to occur by different mechanisms [Book ref. 80, pp. 84–87]. TMV assembly apparently occurs in the plant cell cytoplasm, although it has been suggested that some TMV assembly may occur in chloroplasts since transcripts of ctDNA have been detected in purified TMV virions [Book ref. 80, pp. 73–79]. Initiation of TMV assembly occurs by interaction between ringshaped aggregates (‘discs’) of coat protein (each disc consisting of two layers of 17 subunits) and a unique internal nucleation site in the RNA: a hairpin region ca. 900 nucleotides from the 3′ end in the common strain of TMV. (Any RNA – including e.g. subgenomic RNAs – containing this site may be packaged into virions.) The discs apparently assume a helical form on interaction with the RNA, and assembly (elongation) then proceeds in both directions (but much more rapidly in the 3′ -to5′ direction) from the nucleation site. [Review of structure and assembly: JGV (1984) 65 253–279.] tobacco necrosis virus (TNV) A PLANT VIRUS which can infect a range of angiosperms; transmission occurs via Olpidium spp and can occur mechanically under experimental conditions. Symptoms of TNV infection range from severe necrosis (e.g. in Augusta disease of tulips) to local necrotic leaf lesions (e.g. in tobacco seedlings). Virion: icosahedral, ca. 28 nm diam., containing one polypeptide species (MWt ca. 22600); genome: a single molecule of linear positive-sense ssRNA (MWt ca. 1.3–1.6 × 106 ) with the 5′ -terminal sequence: ppApGpU. . . . TNV-infected plant cells may also contain a SATELLITE VIRUS: an icosahedral, ssRNA-containing virus [structure: JMB (1982) 159 93–108] which is completely dependent on the presence of

[TIM (1998) 6 228–233]. (See also DISSEMINATED INTRAVASCULAR COAGULATION and other cytokine-associated conditions listed under CYTOKINES.) In some individuals, susceptibility to a severe form of MALARIA has been found to correlate with a variant form of the TNF-a promoter [Nature (1994) 371 508–510], and an increased susceptibility to endotoxic shock appears to correlate with enhanced synthesis of TNF [JAMA (1999) 282 561–568]. The apparent link between levels of TNF and pathogenesis has suggested that benefit may be obtained, in certain cases, from the use of ligands that sequester TNF and prevent its binding to specific cell-surface receptors; such anti-TNF ligands include etanercept and the monoclonal antibody infliximab. TNF-a exists in both soluble (secreted) and membraneassociated forms, both forms being active. TNF-b (also called lymphotoxin a) is produced by activated lymphocytes, and is characteristic of the Th1 subset of T cells. TNF-b resembles TNF-a in its activities – many of which coincide with the activities of INTERLEUKIN-1; unlike IL-1, however, TNF can trigger apoptosis in a target cell. The cell-surface receptors of tumour necrosis factor are designated p55 (= CD120a) and p75 (= CD120b) and they occur on a wide range of cells. Each type of receptor can apparently serve as a binding site for both forms of TNF; however, the two receptors may have distinct roles in TNF activity, and p75 may have a subordinate role. Following endotoxaemia, the peripheral circulation contains raised levels of soluble (cell-free) TNF receptors; this may be a protective mechanism which down-regulates the effects of TNF on host cells. The binding of TNF to its receptor may give rise to various effects ranging from stimulation to apoptosis – according to the particular signalling pathway which is activated within the target cell. Currently, these pathways (and the factors which influence the choice of pathway) are incompletely understood, but apoptosis seems to involve part of the cytoplasmic side of the TNF receptor – a region called the ‘death domain’. Following TNF–receptor binding, the death domain appears to associate with certain cytoplasmic factors – including TRADD (TNF receptor-associated death domain protein) and a serine threonine kinase called RIP (receptor interacting protein); RIP may activate caspase(s) such as IL-1b-converting enzyme (ICE) (leading to APOPTOSIS) or it may phosphorylate (and inactivate) the inhibitor IkB, thus activating the nuclear transcription factor NF-kB. tnpA gene See Tn3. TnphoA See TRANSPOSON MUTAGENESIS. tnpM gene See Tn21. tnpR gene See Tn3. toadstool Any umbrella-shaped basidiocarp, but particularly one which is inedible or poisonous. tobacco diseases For diseases of the tobacco plant see e.g. GRANVILLE WILT, PERONOSPORA (blue mould), POTATO VIRUS Y (e.g. veinal necrosis), TOBACCO MOSAIC VIRUS, TOBACCO NECROSIS VIRUS and WILDFIRE DISEASE. tobacco etch virus See POTYVIRUSES. tobacco leafcurl virus See GEMINIVIRUSES. tobacco mosaic virus (TMV) The type member of the TOBAMOVIRUSES. The TMV virion is a tubular filament (ca. 300 × 20 nm, central hole approx. 2 nm diam., S20 w ca. 194); it comprises coat protein subunits (MWt ca. 17500) arranged in a single right-handed helix with the ssRNA intercalated between the turns of the helix (ca. three nucleotides per protein subunit). 780

TOL plasmid TNV for its replication. The satellite can be transmitted by the same mechanisms as TNV, and may influence the nature of the symptoms in the infected plant. TNV (A strain) is the type member of a taxonomic group (the tobacco necrosis virus group); a possible member of this group is cucumber necrosis virus. tobacco necrotic dwarf virus See LUTEOVIRUSES. tobacco rattle virus See TOBRAVIRUSES. tobacco ringspot virus See NEPOVIRUSES. tobacco streak virus See ILARVIRUSES. tobacco vein distorting virus See LUTEOVIRUSES. tobacco vein mottling virus See POTYVIRUSES. tobacco veinal necrosis disease See POTATO VIRUS Y. tobacco yellow dwarf virus See GEMINIVIRUSES. tobacco yellow net virus See LUTEOVIRUSES. tobamoviruses A group of PLANT VIRUSES in which the virion is a rigid filament consisting of one molecule of linear, positivesense ssRNA associated with a single type of coat polypeptide. Type member: TOBACCO MOSAIC VIRUS; other members: e.g. cucumber green mottle mosaic virus, cucumber 4 virus, tomato mosaic virus. A group of morphologically similar viruses which are transmitted by members of the Plasmodiophoromycetes (Polymyxa, Spongospora) – including e.g. beet necrotic yellow vein virus, peanut clump virus, potato mop top virus, soilborne wheat mosaic virus – were tentatively included in the tobamoviruses, but see SOIL-BORNE WHEAT MOSAIC VIRUS. tobramycin 3′ -DeoxyKANAMYCIN B. tobraviruses (tobacco rattle virus group) A group of bipartite ssRNA-containing PLANT VIRUSES which have a wide host range (including monocots and dicots) and which are transmitted primarily by nematodes (Paratrichodorus and Trichodorus spp) but also via seeds and (sometimes) mechanically; the viruses persist in, but do not replicate in, the nematode vector. Type member: tobacco rattle virus (TRV) (PRN isolate); other member: pea early-browning virus. Possible member: peanut clamp virus. Symptoms of tobravirus infection typically include necrosis; TRV can cause e.g. SPRAING in potatoes. Virion: tubular, consisting of a helix (pitch 2.5 nm) of proteincoated linear positive-sense ssRNA; two types of particle occur: one (L particle) is ca. 180–215 nm long and contains RNA1 (MWt ca. 2.4 × 106 ), the other (S particle) is 46–114 nm long (depending on isolate) and contains RNA2 (MWt ca. 0.6–1.4 × 106 ). RNA1 can be replicated in plant cells in the absence of RNA2, and L particles (but not S particles) can alone cause lesions in the host plant; however, both L and S particles are necessary for the formation of progency virions (RNA2 encodes the coat protein). Todd–Hewitt broth A medium used for the culture of certain Streptococcus spp. It contains an infusion of fat-free beef heart, peptone, glucose, sodium chloride, and a buffer system (sodium bicarbonate and disodium hydrogen phosphate); pH: 7.8. Todd unit (TU) A unit used to express the antibody titre in an ANTISTREPTOLYSIN O TEST; it has been defined as the minimum amount of serum which can neutralize 2.5 minimum haemolytic doses of a standard preparation of streptolysin O. tofu An intermediate in SUFU production. Tofu may itself be used as a food. Togaviridae A family of enveloped ssRNA-containing VIRUSes, most of which can infect a wide range of vertebrates; most members also infect arthropods which act as VECTORS (cf. ARBOVIRUSES). The family includes a number of important pathogens of man and animals, some of which can be transmitted transplacentally and can cause abortion or abnormalities in the

infected fetus. Arthropod vectors (which remain infected for life) are apparently unharmed. The Togaviridae contains four genera (members of a genus being serologically related to each other but unrelated to those of other genera): ALPHAVIRUS, ARTERIVIRUS, PESTIVIRUS and RUBIVIRUS; possible members of the family include LACTATE DEHYDROGENASE VIRUS and carrot mottle virus. [Taxonomy: Intervirol. (1985) 24 125–139.] (cf. FLAVIVIRIDAE.) The togavirus virion is spherical (ca. 50–70 nm diam.) and consists of a nucleocapsid (ca. 28–35 nm diam.) – which is icosahedral in at least some species – surrounded by a lipoprotein envelope. The nucleocapsid is composed of a single type of core protein (C protein) associated with the RNA genome. The envelope bears surface projections (spikes) composed of two major glycoproteins, E1 and E2; in Semliki Forest virus a third glycoprotein, E3, is associated with the spikes, but in other alphaviruses E3 is released into the culture fluid in infected cell cultures. The nature of the glycosylation of these proteins is variable, depending at least in part on the nature of the host cell. The envelope glycoproteins are responsible for haemagglutinating activity and for virus infectivity. [Structure of alphaviruses: see e.g. Cell (2001) 105 5–8.] The virus genome consists of a single molecule of linear positive-sense ssRNA (MWt ca. 4 × 106 ); in those viruses which have been investigated, the RNA is capped and polyadenylated. In alphaviruses, at least, the gene sequence is 5′ nsP1–nsP2–nsP3–nsP4–C–E3–E2–E1-3′ , where nsP1–nsP4 are non-structural proteins (apparently RNA-dependent RNA polymerase components). [Nucleotide sequence of Sindbis virus: Virol. (1984) 133 92–110.] Togavirus replication occurs in the host cell cytoplasm; the process has been studied chiefly in the alphaviruses Semliki Forest virus and Sindbis virus. In these viruses, the nonstructural proteins are synthesized directly from the (42S) genome-length (+)-strand RNA, while structural proteins are translated from capped and polyadenylated 26S subgenomic RNA which is initiated internally on a full-length (−)-strand template. (Rubella virus employs a similar strategy, producing 40S genome-length and 24S subgenomic RNAs [JV (1984) 49 403–408].) Translation is initiated at a single site, and the proteins are generally cleaved from the nascent polyprotein during translation. The synthesis of each type of viral RNA (full-length (−)-strand, full-length (+)-strand, and subgenomic) is apparently regulated independently; 26S RNA is produced in excess of 42S RNA, and genomic RNA is rapidly encapsidated, so that a large excess of structural over non-structural proteins is achieved. Virus maturation involves budding through the plasma membrane or through intracytoplasmic membranes. [Overview of the replication cycle: Book ref. 148, pp. 1021–1032.] Many alphaviruses induce rapid and dramatic CPE in vertebrate cells (cf. RUBIVIRUS); host cell RNA and protein synthesis is rapidly arrested, and the cells eventually lyse. Some alphaviruses can establish persistent infections in vertebrate cells. [Effects of alphavirus infection on vertebrate cells: Book ref. 150, pp. 465–499.] Invertebrate cells are generally infected persistently with no apparent adverse effects. togaviruses Viruses of the TOGAVIRIDAE. Tokophrya See SUCTORIA. TOL plasmid An IncP-9 Pseudomonas PLASMID (ca. 117 kb) which encodes the capacity to metabolize toluene and xylene. (cf. CAM PLASMID; OCT PLASMID; SAL PLASMID.) [Degradative plasmids of Pseudomonas: Book ref. 198, pp. 295–323.] TOL encodes the enzymes of a two-stage catabolic pathway for the mineralization of toluene and xylene. Initially, these 781

TolA protein tomato top necrosis virus See NEPOVIRUSES. tomato yellow dwarf virus See GEMINIVIRUSES. tomato yellow leafcurl virus See GEMINIVIRUSES. tomato yellow mosaic virus See GEMINIVIRUSES. tomato yellow net virus See LUTEOVIRUSES. tomato yellow top virus See LUTEOVIRUSES. tomaymycin See ANTHRAMYCIN. tombusviruses (tomato bushy stunt virus group) A group of ssRNA-containing PLANT VIRUSES which can infect a wide range of angiosperms. Transmission occurs mechanically and possibly via the soil. Type member: tomato bushy stunt virus (TBSV); other members: e.g. artichoke mottled crinkle virus, carnation Italian ringspot virus, Cymbidium ringspot virus, and eggplant mottled crinkle virus. (Other ‘possible members’ – e.g. carnation mottle virus, saguaro cactus virus, and turnip crinkle virus – appear on the basis of subgenomic dsRNA analysis to have a different genome organization and may constitute a separate group [Book ref. 80, pp. 80–83].) [Serological relationships among tombusviruses: JGV (1986) 67 75–82.] Virion: icosahedral, 30 nm diam., containing one molecule of linear positive-sense ssRNA (MWt ca. 1.5 × 106 ). The capsid is composed primarily of 180 molecules of a major coat protein. Each coat protein molecule (386 amino acid residues) is folded into three distinct domains (P, S and R): the S domains form the tightly bonded icosahedral shell, the P domains form surface projections, and the (N-terminal) R domains apparently project inwards and may bind the genomic RNA; the P and S domains are linked via a flexible hinge region. [Virion structure: Book ref. 81, pp. 43–50.] Within infected plant cells, the virus particles occur in the cytoplasm and nucleus (often associated with the nucleolus), sometimes forming crystalline arrays; compact membranous inclusion bodies (‘multivesicular bodies’) occur in the cytoplasm. tomentose Downy; woolly. tomentum (lichenol.) A downy or felted mat of hyphae which occurs (usually) on the lower surface of the thallus in certain foliose lichens. tomite A typically small, motile, non-feeding stage in the life cycles of certain protozoa; it is generally formed, within a CYST, by the division of a cell called a tomont. In e.g. ICHTHYOPHTHIRIUS the tomite acts as a THERONT. In members of the Apostomatida the tomite itself eventually encysts at a site on a suitable host (becoming a phoront) and subsequently develops into a cell capable of feeding (a trophont) – which later develops into a tomont; in some apostomes a stage known as a protomite occurs between the tomont and tomite stages. tomont See TOMITE. TonA protein (FhuA protein) In Escherichia coli: an OUTER MEMBRANE protein encoded by the tonA gene; it acts as a receptor for e.g. colicin M and bacteriophages T1 and f80, and is involved in the uptake of albomycin and ferrichrome. TonB protein In e.g. Escherichia coli, a periplasmic protein that shuttles between the cytoplasmic membrane and outer membrane [Mol. Microbiol. (2003) 49 869–882], supplying energy (from pmf) to the outer membrane for the uptake of e.g. ferric iron–chelate complexes (see SIDEROPHORES); it is also involved e.g. in the uptake of VITAMIN B12 by BINDING PROTEINDEPENDENT TRANSPORT. The uptake of vitamin B12 across the outer membrane in E. coli is pmf-dependent [JB (1993) 175 3146–3150]; it appears that maximum activity of this (and other) TonB-dependent systems requires the products of exbB and exbD (proteins in the cytoplasmic membrane) which may stabilize TonB. ExbB and

substrates are oxidized to their respective carboxylic acids. Such oxidation involves enzymes encoded by the upper operon of the TOL plasmid; the Pu promoter of the upper operon is regulated by an enhancer-dependent sigma factor (s54 ; see SIGMA FACTOR) in association with the activator protein XylR. The meta operon of TOL encodes enzymes involved in aromatic ring fission and subsequent formation of pyruvate and acetaldehyde (which enter the TCA cycle). [Regulation of the upper and meta operons of the TOL plasmid: EMBO (2001) 20 1–11 (4–6).] In strains of Pseudomonas carrying the Tol plasmid, the availability of iron may be an important factor in the oxidative metabolism of toluene [AEM (2001) 67 3406–3412]. TolA protein See COLICINS. TolB protein See COLICINS. toleragen See IMMUNOLOGICAL TOLERANCE. tolerance (immunol.) See IMMUNOLOGICAL TOLERANCE. tolG gene See OMP. tolnaftate (2-naphthyl-N-methyl-N-(m-tolyl) thiocarbamate) An ANTIFUNGAL AGENT which is effective in the topical treatment of dermatophyte infections but which has little or no activity against most other fungi or bacteria. tolQ gene See TONB PROTEIN. TolQ protein See COLICINS. tolR gene See TONB PROTEIN. TolR protein See COLICINS. toluidine blue A blue metachromatic basic thiazine DYE used e.g. in ALBERT’S STAIN and for VITAL STAINING. Tolypocladium See HYPHOMYCETES; see also CYCLOSPORIN A. tolypomycins See ANSAMYCINS. Tolyposporium See USTILAGINALES. Tolypothrix See SCYTONEMA. tolZ gene See FTSH. tomatine A glycoalkaloid SAPONIN present in high concentrations in green tomatoes. It is toxic to many fungi; in mutant strains of Fusarium solani which are resistant to tomatine the cytoplasmic membrane has been found to have lower-than-normal levels of sterols. tomato apical stunt viroid See VIROID. tomato aspermy virus See CUCUMOVIRUSES. tomato black ring virus See NEPOVIRUSES. tomato bunchy top viroid See VIROID. tomato bushy stunt virus See TOMBUSVIRUSES. tomato golden mosaic virus See GEMINIVIRUSES. tomato mosaic virus See TOBAMOVIRUSES. tomato (Peru) mosaic virus See POTYVIRUSES. tomato planta macho viroid See VIROID. tomato ringspot virus See NEPOVIRUSES. tomato spotted wilt virus (TSWV) A PLANT VIRUS which appears to be unrelated to other known viruses, although it has some properties resembling those of bunyaviruses. Virion: spherical, enveloped, ca. 82 nm diam., containing 4 major and up to 3 minor proteins. Genome: ssRNA (one negative-sense and two AMBISENSE pieces). TSWV can infect a wide range of host plants. Infected cells contain granular cytoplasmic inclusion bodies. Immature virions are each surrounded by two lipoprotein membranes, but the mature virions each have a single envelope and occur in groups within membranous vesicles. Maturation resembles that of the BUNYAVIRIDAE. Transmission occurs (circulatively) via thrips (Thysanoptera); only the larval stage of the insect can acquire the virus from an infected plant, but once acquired the virus is retained by the insect for life. TSWV can also be transmitted mechanically under experimental conditions. 782

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ExbD seem to be replaceable, to some extent, by the products of tolQ and tolR. TonB is involved in the susceptibility of the cell to bacteriophage f80. It is also required for the uptake of group B colicins: colicins B, D, Ia, Ib, M, V, 5 and 10 [colicin import into Escherichia coli cells: JB (1998) 180 4993–5002]. (See also FEPA PROTEIN and TSX PROTEIN.) tonoplast The membrane which forms the boundary of an intracellular vacuole. tonsillitis Inflammation of the tonsils, commonly caused by Streptococcus pyogenes. (See also OTITIS MEDIA, QUINSY, RHEUMATIC FEVER.) Tontonia See OLIGOTRICHIDA. tooth diseases See DENTAL CARIES and PERIODONTITIS. top-fermenting yeast See BREWING. top necrosis (plant pathol.) Necrosis (death) of the terminal bud or of the entire top of a plant. topical (med., vet.) Local, i.e., restricted to a particular region of the body; not SYSTEMIC. topo I, topo II, etc. Syn. TOPOISOMERASE type I, topoisomerase type II, etc. topoisomer Topoisomers are molecules which differ from one another only in their topological properties. For example, a given dsDNA molecule may occur in a number of topologically distinct forms: linear, relaxed circular, or supercoiled circular (ds cccDNA molecules with different linking numbers, but otherwise identical, are topoisomers); interconversion of topoisomers necessitates strand breakage and/or joining. (See also DNA.) topoisomerase (DNA topoisomerase) Any enzyme which can convert one topological isomer of cccDNA to another; topoisomerases can e.g. alter the linking number (Lk) of a cccDNA molecule (see DNA) and (at least in vitro) can form and resolve knots and CATENANES – i.e. the reactions catalysed by a topoisomerase can be intermolecular or intramolecular. All such topological conversions involve transient breakage of either one or both strands of DNA. Type I (= type 1) topoisomerases (also called untwisting, relaxing or nick-closing enzymes, or swivelases) break only one strand of DNA; in a ds cccDNA molecule, the unbroken strand is passed through the break before re-sealing, thus changing the value of Lk by one for each such event. Type II (= type 2) topoisomerases break both strands of DNA in a ds cccDNA molecule; a (double-stranded) segment of DNA from elsewhere in the molecule is then passed through the break (without strand rotation) before re-sealing – each such event changing the value of Lk by two. Both types of enzyme are found in both prokaryotic and eukaryotic cells. Certain topoisomerases are the targets of QUINOLONE ANTIBIOTICS (q.v.). An example of a type I topoisomerase is the ! (omega) protein of Escherichia coli (E. coli topoisomerase I, or ‘topo I’); in vitro, this enzyme can e.g. partially relax negatively (but not positively) supercoiled DNA, can introduce topological knots into ss cccDNA, and can convert complementary ss cccDNA circles into completely base-paired ds cccDNA. The primary in vivo role of topo I appears to be the relaxation of negative supercoiling; topo I is necessary e.g. for chromosomal DNA REPLICATION. Topo III (encoded by gene topB ) is another type I topoisomerase in E. coli; like topo I, this enzyme can relax negative supercoiling (and e.g. form and resolve knots) in vitro, but its in vivo role has not been established. Type II topoisomerases include GYRASE, REVERSE GYRASE, bacteriophage T4 topoisomerase (gp39, 52, 60), and topoisomerase

II′ ,

(topo an enzyme from E. coli which contains gyrase subunit A and a part of gyrase subunit B). The T4 enzyme and topo II′ have been reported to relax positively or negatively supercoiled DNA. In vitro, type II topoisomerases can form and resolve catenanes and can also form and resolve knots. In a model for the mechanism of type II topoisomerases, binding of the enzyme initially introduces a sharp bend in the DNA, the enzyme adopting a specific orientation with respect to the bend and subsequently promoting unidirectional passage of the strands through the break [PNAS (2001) 98 3045–3049]. Topoisomerase IV is a type II enzyme encoded by genes parC and parE in E. coli. This enzyme can e.g. relax more fully those negatively supercoiled molecules of DNA which have been partially relaxed by topo I; topo IV appears to be responsible – solely – for decatenation and for the resolution of knots in E. coli [GD (2001) 15 748–761]. topological winding number See DNA. topotaxis A behavioural response in which a motile organism moves (directly or indirectly) towards or away from a directional stimulus. (cf. PHOBIC RESPONSE.) Torbal jar See MCINTOSH AND FILDES’ ANAEROBIC JAR. TORCH diseases A group of diseases – comprising TOXOPLASMOSIS, RUBELLA, CYTOMEGALIC INCLUSION DISEASE, and HERPES SIMPLEX – each of which can cause abortion, stillbirth, severe neonatal disease, and sometimes fetal tissue damage with consequent developmental abnormalities. toroidal DNA See DNA TOROID. Toroviridae A family of enveloped RNA viruses proposed to include the BERNE VIRUS and serologically related viruses: e.g. BREDA VIRUS and some human gastroenteritis viruses. torr See PASCAL. Torula A genus of fungi of the HYPHOMYCETES. T. herbarum is common e.g. on dead grasses – forming dark, velvety colonies, and dark conidia in chains. torula yeast A food yeast, Candida utilis (= Torulopsis utilis), grown e.g. on ethanol or sulphite liquor waste (see SINGLE-CELL PROTEIN); the yeast is pasteurized and dried before use. It is a rich source of protein and vitamins and is used medicinally and as a food additive. torularhodin See CAROTENOIDS. Torulaspora A genus of yeasts (family SACCHAROMYCETACEAE) in which the cells are globose or ellipsoidal; vegetative reproduction occurs by multilateral budding. Pseudomycelium is not formed. Vegetative cells are predominantly haploid (cf. SACCHAROMYCES). Ascus formation is preceded by conjugation – usually between a cell and its bud, but sometimes between independent cells; asci are persistent. Ascospores: globose or ellipsoidal, smooth- or rough-surfaced, 1–4 per ascus. Glucose and certain other sugars are fermented vigorously; NO3 − is not assimilated. Species: T. delbrueckii (anamorph: Candida colliculosa), T. globosa (formerly e.g. Saccharomyces kloeckerianus), and T. pretoriensis (formerly e.g. Saccharomyces pretoriensis); strains have been isolated from fruit juice, wines, fermenting cucumber brines, soil, faeces, etc. [Book ref. 100, pp. 434–439.] Torulopsis A genus of yeasts (class HYPHOMYCETES), now generally included within the genus CANDIDA [Book ref. 100, p. 841]. Hyphae and pseudohyphae are generally not formed. torulopsosis A MYCOSIS, now regarded as a form of CANDIDIASIS, caused by Candida glabrata (= Torulopsis glabrata). The disease (in man) is usually systemic, involving lungs, kidney, heart, CNS etc. torulosis Syn. CRYPTOCOCCOSIS. total cell count See COUNTING METHODS. 783

Totiviridae Totiviridae See MYCOVIRUS. touchdown PCR Repetition of a given PCR assay with a stepwise decrease in annealing temperature in each run; the object is to find the lowest annealing temperature (for the given assay) which will permit normal primer binding but avoid the problem of mispriming (i.e. binding of primers to inappropriate sequences). (The procedure thus seeks a level of stringency which promotes maximum specificity of primer binding.) [Examples of use: NAR (1991) 19 4008; JCM (1999) 37 1274–1279.] tower fermenter See FERMENTER. toxaemia (toxemia) The condition in which TOXINS are present in the blood. (cf. PYAEMIA; SEPTICAEMIA.) toxemia Syn. TOXAEMIA. toxic Poisonous; harmful. (cf. TOXIN.) toxic epidermal necrolysis (TEN) A syndrome characterized by erythema followed by separation of the outer epidermis from the basal layer of the skin; it may be caused by ETproducing staphylococci (staphylococcal TEN – see SCALDED SKIN SYNDROME) or by a hypersensitivity reaction to certain drugs (allergic TEN). toxic food poisoning See FOOD POISONING. toxic shock syndrome (TSS) A severe, often fatal, illness characterized by fever, vomiting, diarrhoea and hypotension; late symptom: a sunburn-like rash with peeling of the skin, especially on palms and soles. In menstruating women, TSS is associated with the use of vaginal tampons. In children, TSS may follow burns or scalds etc.; encephalitic symptoms may occur in very young children in whom cytokines may cross the blood–brain barrier. TSS is caused by certain of the toxins that are classified as SUPERANTIGENS: the B and C enterotoxins of Staphylococcus aureus, the toxic shock syndrome toxin 1 (TSST-1) of S. aureus (known earlier as enterotoxin F, pyrogenic exotoxin C and toxic shock toxin), and the superantigen A of Streptococcus pyogenes. The gene that encodes TSST-1 occurs on a mobile PATHOGENICITY ISLAND – possibly accounting for the spread of toxigenicity in S. aureus [Mol. Microbiol. (1998) 29 527–543]. Bacteraemia is uncommon in staphylococcal TSS, common in streptococcal TSS. In the acute phase of staphylococcal TSS there is a higher proportion of e.g. Vb2 T cells, and raised levels of e.g. IL-2, IL-4, TNF-a, TNF-b and IFN-g. [Multiplex PCR for detection of the genes of S. aureus enterotoxins B and C, and TSST-1: JMM (1998) 47 335–340. Multiplex PCR for detection of genes for S. aureus enterotoxins, exfoliative toxins, toxic shock syndrome toxin 1 and methicillin resistance: JCM (2000) 38 1032–1035.] toxic shock syndrome toxin 1 (TSST-1) See TOXIC SHOCK SYNDROME AND SUPERANTIGEN. toxicoinfection See infant BOTULISM. toxicosis Any human or animal disease caused by poisoning (see e.g. MYCOTOXICOSIS). toxicyst A type of tubular EXTRUSOME which occurs in many carnivorous ciliates (e.g. Actinobolina, Didinium, Dileptus); on activation, the tubular structure everts, penetrates the prey, and apparently introduces toxin(s) and proteolytic enzymes. toxigenic (toxinogenic) Refers to an organism which can produce one or more TOXINS. toxin In a microbiological context: any of various microbial products or components which, at low concentrations, can act in a specific way on cells or tissues in a higher (multicellular) organism and cause local and/or systemic damage, or death – such an agent (alone, or with other toxin(s) and/or virulence factor(s)) being responsible, directly or indirectly, for at least some aspect

of pathogenesis. In many cases there is insufficient information on the role of a given agent in pathogenesis to decide whether or not it conforms to the above definition. In some cases the known activity of a toxin is sufficient to account for all the observed features of pathogenesis in a given disease. For example, the zinc-endopeptidase activity of tetanus toxin, which blocks neuroexocytosis (see TETANOSPASMIN), adequately explains why inhibitory neurotransmitter is not released into the synaptic cleft. In other cases, the activity of a toxin depends on one or more additional virulence factors. For example, toxigenic strains of Bacillus anthracis can cause ANTHRAX only if the cells have an antiphagocytic capsule. Again, the virulence of ETEC depends on plasmid-encoded fimbriae with which the bacteria adhere to the epithelium of the small intestine. While tetanus toxin is involved directly in the mechanism of pathogenesis, the pathogenic role of some toxins is due partly or solely to their ability to behave as MODULINS – e.g. the B and C enterotoxins and TSST-1 of Staphylococcus aureus (see TOXIC SHOCK SYNDROME and SUPERANTIGEN). Many types of bacterial toxin can induce cytokines, the exotoxins being particularly potent inducers. Not all toxic microbial substances are called ‘toxins’. For example, generally not regarded as toxins are those products (e.g. lactic acid, hydrogen sulphide) which are significantly toxic to animals or plants only when present in relatively high concentrations (cf. ACIDOSIS sense 1 and SUFFOCATION DISEASE) – or which have an essentially physical role in causing or enhancing disease (e.g. alginate in CYSTIC FIBROSIS). Also traditionally excluded from the category ‘toxin’ are those microbial products which, at low concentrations, are toxic to other microorganisms (e.g. ANTIBIOTICS, BACTERIOCINS). The definition of a toxin may be based on criteria which differ in different disciplines. Thus, medical and veterinary workers may accept as toxins: (i) certain microbial enzymes which act as AGGRESSINS; (ii) substances toxic to cells in vitro but whose role in causing or exacerbating disease under natural conditions is unknown; (iii) substances produced at a site remote from the ‘target’ organism (see e.g. BOTULISM and paralytic SHELLFISH POISONING). Plant pathologists may not accept that enzymes can be toxins, and may not accept as toxins substances in categories (ii) and (iii) [discussion: Book ref. 58. pp 139–140]. A given toxin may be categorized according to the nature of the organism producing it (e.g. mycotoxin, phycotoxin), the nature of the organism affected by it (e.g. ichthyotoxin), the type of cell or tissue affected (e.g. ENTEROTOXIN, HAEMOLYSIN sense 2, hepatotoxin, LEUCOCIDIN, NEUROTOXIN) etc. (See also ENDOTOXIN and EXOTOXIN.) However, such categories are sometimes imprecise and may be misleading: e.g. an ‘ichthyotoxin’ may be toxic to organisms other than fish, and terms such as ‘hepatotoxin’ and ‘enterotoxin’ may be applied to toxins which can affect other types of cell and tissue. For algal toxins see: PHYCOTOXIN. For fungal toxins see: MYCOTOXIN. For protozoal toxins see amoebic DYSENTERY. For bacterial toxins see: ANTHRAX TOXIN, BOTULINUM TOXIN, CHOLERA TOXIN, DELTA-ENDOTOXIN, DIPHTHERIA TOXIN, EPIDERMOLYTIC TOXIN, EXOTOXIN A, PERTUSSIS TOXIN, PHYTOTOXIN, RTX TOXINS, SHIGA TOXIN, TETANOSPASMIN. (See also HAEMOLYSIN (sense 2), HYALURONATE LYASE, LEUCOCIDIN, THIOL-ACTIVATED CYTOLYSINS.) [Bacterial protein toxins: Book ref. 206.] toxin co-regulated pili (TCP) See CHOLERA, BACTERIOPHAGE CTX8 and PATHOGENICITY ISLAND. 784

Trachelophyllum toxinogenic Syn. TOXIGENIC. toxoid A TOXIN which has been modified (e.g. by treatment with formalin) so as to destroy its toxicity without affecting its specific immunogenicity. Thus, antibody formed against a toxoid can inactivate the corresponding toxin; toxoids are therefore useful in VACCINES. toxoneme A MICRONEME in Toxoplasma. Toxoplasma A genus of parasitic, facultatively heteroxenous protozoa (suborder EIMERIORINA); the organisms have been classified by some authors [AP (1982) 20 403–406] in the genus ISOSPORA. T. gondii (= I. gondii ) is an intracellular parasite and the causal agent of TOXOPLASMOSIS (q.v. for life cycle; see also PHAGOCYTOSIS); the sporozoites of T. gondii are uninucleate, banana-shaped, motile cells ca. 5–8 × 1–2 µm, but smaller, stumpy or ovoid cells occur within cysts. In the INTERMEDIATE HOST (birds, non-felines, man) only asexual reproduction occurs; in the FINAL HOST (members of the cat family) reproduction occurs asexually in extra-intestinal tissues as well as sexually in the intestinal tissues. T. gondii forms disporic, tetrazoic oocysts (10–15 µm) which undergo SPORULATION outside the (feline) host. Once sporulated, oocysts remain infective in soil for e.g. 1–2 years; they can be rendered uninfective e.g. by heating to 90° C for 30 sec [AP (1982) 20 310]. Toxoplasma dye test (Sabin–Feldman dye test) A serological test used to detect and quantify antibodies to Toxoplasma gondii. The patient’s serum is heated (56° C/30 min) and a range of dilutions is prepared. To each dilution is added (i) live laboratory-cultured cells of T. gondii, and (ii) normal serum containing a known amount of ‘accessory factor’ – i.e., COMPLEMENT [JID (1980) 141 366–369]; each test dilution is then incubated. In the presence of antibodies (positive test) the cells are damaged and are unable to take up an indicator dye (alkaline methylene blue); this is determined by microscopy. In the absence of antibodies the (undamaged) cells take up the dye. Toxoplasmea A class of parasitic protozoa (subphylum SPOROZOA); organisms of this class (e.g. Sarcocystis, Toxoplasma), together with those of the TELOSPOREA and PIROPLASMEA, have been incorporated in the class SPOROZOASIDA. toxoplasmosis An acute or chronic disease of man and other animals (e.g. cat, goat, pig, sheep) caused by Toxoplasma gondii (see TOXOPLASMA). In man, infection occurs by ingestion of sporulated oocysts (present e.g. in infected cat faeces) or of ‘tissue cysts’ in raw or insufficiently cooked infected meats. Infection may be asymptomatic, there may be mild lymphadenopathy, or the disease may be generalized with e.g. hepatitis, pneumonia, myalgia, meningoencephalitis etc; latent infection may persist for years. In the acute phase of the disease the parasite multiplies endodyogenously in cells of various tissues (including e.g. macrophages), forming pseudocysts; a pseudocyst (= group stage) is the remains of a host cell packed with rapidly dividing cells (endozoites, tachyzoites) of the parasite. (See also PHAGOCYTOSIS.) If the host survives, the disease enters the chronic phase in which the parasite localizes in certain tissues (e.g. brain, eye, skeletal muscles, heart), forming tissue cysts; a tissue cyst (also called a pseudocyst or meront) is a structure (ca. 50–100 µm) containing cells of the parasite (cystozoites, bradyzoites) which are undergoing slow endodyogenous division. Toxoplasmosis may be transmitted transplacentally; the congenital disease often involves lesions in the brain and/or eyes and may lead to blindness, mental retardation, or death (cf. TORCH DISEASES). Lab. diagnosis: e.g. (i) inoculation of material from lesions into mice and examination of smears or sections post mortem; (ii) serological tests – e.g. a CFT and the TOXOPLASMA DYE TEST; (iii) an indirect immunofluorescence test (or

an ELISA-based test) for antibodies. A PCR-based assay for T. gondii (in HIV-positive patients) was reported to have a specificity of 100% but poor sensitivity (only 25%); it was nevertheless suggested that this assay may find use in differentiating between cerebral toxoplasmosis and clinically similar disease [JCM (1997) 35 2639–2641]. Chemotherapy: e.g. PYRIMETHAMINE with sulphonamides. In the cat infection with T. gondii may occur on ingestion of mature oocysts (from other cats) or tissue cysts (in avian or mammalian prey); T. gondii develops in both extra-intestinal and intestinal tissues. In the intestine the parasite multiplies by endodyogeny, endopolygeny and schizogony and forms macrogametes and biflagellate microgametes. Macrogametes are fertilized in situ, and the zygote develops into an oocyst which is shed, unsporulated, in the faeces. Adult cats are usually symptomless; kittens may respond with diarrhoea and death or with anorexia and wasting. Congenital toxoplasmosis occurs e.g. in goats and sheep, and is one cause of abortion in sheep. [AP (1982) 20 296–332.] Toxothrix A genus of colourless GLIDING BACTERIA which occur e.g. in cold, iron-containing springs; the trichomes give rise to bundles of thin, iron-oxide-containing inanimate filaments. [Habitat and culture: Book ref. 45, pp. 409–411.] ToxR, ToxS, ToxT See BACTERIOPHAGE CTX8. TPA 12-O-tetradecanoylphorbol-13-acetate. (See also ZEBRA.) TPB− Tetraphenylborate: see CHEMIOSMOSIS. TPHA test Treponema pallidum haemagglutination test. A TREPONEMAL TEST, involving passive haemagglutination, in which an absorbed serum (cf. FTA-ABS TEST) is tested for its ability to agglutinate tanned erythrocytes sensitized with antigens from the Nichol’s strain of Treponema pallidum. In primary SYPHILIS the TPHA test is less sensitive than the FTA-ABS test, but these tests have similar sensitivities in other stages of the disease. TPI test (Treponema pallidum immobilization test) A TREPONEMAL TEST previously used extensively as a confirmatory test in the diagnosis of SYPHILIS; the antibodies detected by the test are specific to Treponema pallidum and some other Treponema spp. Essentially, the test depends on the immobilization of living (motile) cells of T. pallidum in the presence of specific antibodies and COMPLEMENT. To the serum under test is added a standardized suspension of T. pallidum and a volume of fresh guinea-pig serum as a source of complement; the whole is incubated anaerobically for 18 hours at 37° C and examined microscopically. In a positive reaction a specified proportion of treponemes is immobilized. TPMP+ Triphenylmethylphosphonium: see CHEMIOSMOSIS. TPN Triphosphopyridine nucleotide (NADP): see NAD. TPP THIAMINE pyrophosphate. tra gene See TRANSFER OPERON and F PLASMID. tra operon See TRANSFER OPERON. traA gene See F PLASMID. tracheal antimicrobial peptide See DEFENSINS. tracheal cytotoxin In WHOOPING COUGH: a toxin (apparently a fragment of PEPTIDOGLYCAN from the pathogen) which kills epithelial cells to which the pathogen is adherent. Trachelomonas A genus of EUGLENOID FLAGELLATES in which the cells closely resemble those of EUGLENA except that each is enclosed within a yellowish to reddish-brown, round or ovoid LORICA composed mainly of ferric hydroxide and manganese oxides; the lorica is ornamented with spines in some species. The emergent flagellum protrudes through the lorica, and the organisms are free-swimming. Trachelophyllum A genus of carnivorous ciliates (subclass GYMNOSTOMATIA) which occur e.g. in some SEWAGE TREATMENT 785

Tracheloraphis plants. Cells: elongated, with uniform body ciliature and a cytostome at the end of the narrower anterior region. Tracheloraphis See KARYORELICTID GYMNOSTOMES. Trachelostyla See HYPOTRICHIDA. Trachipleistophora See MICROSPORIDIOSIS. trachoma A potentially blinding disease of the eye which, in nature, affects only man; the causal agent is Chlamydia trachomatis (see CHLAMYDIA). Infection occurs contaminatively. Initially there is a follicular CONJUNCTIVITIS affecting particularly the margin of each upper eyelid (tarsal conjunctivae) – but also affecting the inner surfaces of the eyelids (palpebral conjunctive) and the (bulbar) conjunctiva on the anterior surface of the eyeball. Discharging follicles, containing accumulations of macrophages, polymorphs and lymphocytes, develop within the conjunctival tissues, the latter subsequently becoming scarred. The contraction of scarred tissues leads to inturned eyelids. The consequent abrasion of the cornea by the eyelashes causes ulceration, scarring and impairment/loss of vision. A thin fibrovascular membrane (pannus) develops on the surface of the cornea. Lymphoid follicles may develop at the cornea–sclera junction; on healing, these leave characteristic depressions (Herbert’s pits). The mechanism of pathogenesis is not understood; it has been suggested that it may involve cell-mediated HYPERSENSITIVITY. Chemotherapeutic agents commonly used include e.g. TETRACYCLINES. Laboratory diagnosis typically involves the examination of specimens by e.g. IMMUNOFLUORESCENCE or enzyme immunoassay techniques. [Book ref. 193, pp. 135–170.] Trachyspora See UREDINIOMYCETES. trachytectum Syn. EXOSPORIUM (sense 2). tractellum A (eukaryotic) FLAGELLUM which ‘pulls’ the cell forwards. TRADD See TNF. traffic ATPase (1) Syn. ABC TRANSPORTER. (2) Syn. BINDING PROTEIN-DEPENDENT TRANSPORT SYSTEM. Trager duck spleen necrosis virus See AVIAN RETICULOENDOTHELIOSIS VIRUSES. traI gene See F PLASMID. trailer (mol. biol.) See MRNA. traJ gene See F PLASMID. traM gene See F PLASMID. trama The sterile (i.e., non-generative) inner tissue of a LAMELLA or DISSEPIMENT or of the ‘teeth’ of members of the Hydnaceae. (See also BILATERAL TRAMA.) Trametes A genus of lignicolous fungi of the APHYLLOPHORALES (family Polyporaceae) which form basidiocarps in which the hymenophore is porous. T. pini is parasitic on certain trees. For T. versicolor see CORIOLUS. (See also XYLANASES.) trans-acting See CIS-DOMINANCE. trans complementation See CIS–TRANS TEST. transaldolase See Appendix I(b) and RMP PATHWAY. transaminases (of Escherichia coli ) See AMMONIA ASSIMILATION. transcapsidation See PHENOTYPIC MIXING. transcipient A cell which has received DNA from another cell. transconjugant See CONJUGATION (1b) and CONJUGATIVE TRANSPOSITION. transcriptase An RNA POLYMERASE involved in TRANSCRIPTION. (cf. RNA-DEPENDENT RNA POLYMERASE.) transcription The synthesis of an RNA strand in a process in which ribonucleoside 5′ -triphosphates (rNTPs) base-pair sequentially with nucleotides in a template strand and are polymerized in the 5′ -to-3′ direction (with elimination of PPi) by an RNA POLYMERASE; the template strand is DNA in cells and DNA viruses,

RNA in e.g. RNA viruses (see RNA-DEPENDENT RNA POLYMERASE). (cf. REVERSE TRANSCRIPTASE.) (Until recently it has been observed that only one of the two strands of DNA in a gene acts as template in transcription. Interestingly, it has been reported that a certain gene in the fruitfly (Drosophila) contains protein-encoding information in both strands – RNAs synthesized on both template strands being subsequently joined to form a single molecule of mRNA [Nature (2001) 409 1000].) In e.g. Escherichia coli (and other bacteria) initiation of transcription begins when the RNA POLYMERASE (RPase) holoenzyme binds to a PROMOTER. The polymerase core enzyme itself has a high affinity for dsDNA and can bind at (apparently) any site to form a stable, ‘closed’ enzyme–DNA complex in which the DNA strands are not unwound. Interaction of a SIGMA FACTOR with the core enzyme confers on it specificity for a particular class of PROMOTER while greatly reducing its affinity for other DNA sequences. The holoenzyme binds very tightly to its corresponding promoter; initially a ‘closed’ complex is formed, but this is subsequently converted to an ‘open’ complex in which a short region of the DNA bound by the enzyme becomes unwound. The first rNTP can then pair with a base on one of the DNA strands (the start point or start site). A few nucleotides are then incorporated, each being added to the 3′ -OH of the preceding nucleotide; the s factor then dissociates. (The first nucleotide retains its 5′ -triphosphate group.) [Polymerase–promoter interactions: JB (1998) 180 3019–3025.] Elongation is carried out by the RPase core enzyme (possibly in association with the product of the nusA gene, a protein which can bind to the core enzyme but not to the holoenzyme); the polymerase moves along the dsDNA, locally unwinding the strands to expose the ssDNA template, ‘supervising’ the correct base-pairing between incoming rNTPs and the template, and linking the nucleotides in the 5′ -to-3′ direction (antiparallel to the template) with elimination of pyrophosphate. In this way, a transient RNA–DNA hybrid duplex is formed in the region of the enzyme–DNA complex; as the enzyme proceeds, the RNA peels away from the template and the DNA duplex is restored. [Role of RNA polymerase in elongation: JB (1998) 180 3265–3275.] In some cases, transcription of genes or operons occurs divergently (in opposite directions) from closely spaced promoters. This causes an increase in the level of negative supercoiling in the region between polymerases (negative supercoiling being generated behind each advancing polymerase). Such localized accumulation of negative superhelicity may affect the expression of genes/operons [Mol. Microbiol. (2001) 39 1109–1115]. Elongation continues until a specific termination signal (terminator, t) is reached. Terminators in bacteria vary in efficiency and in mechanism of action; secondary structure in the transcript itself appears to be important in effecting termination. In a rho-independent (‘simple’) terminator the RNA transcript of the termination region contains a GC-rich PALINDROMIC SEQUENCE (which can form a stem-and-loop structure) continuous with a run of consecutive uridine (rU) residues at the 3′ end. The stemand-loop structure causes the RPase to pause at the oligo-rU region, and the sequence of rU·dA base pairs (which is relatively unstable) may facilitate the release of the transcript and/or dissociation of the transcription complex. In a rho-dependent (‘complex’) terminator, the transcript may contain a stem-andloop structure (which is not particularly GC-rich), but there is generally no oligo-rU sequence or any other apparent consensus sequence. In this case termination requires the participation of 786

transduction a protein, the rho (r) factor ; the r factor is apparently active in hexameric form, has RNA-dependent NTPase activity (which is necessary for termination), and apparently interacts directly with the RNA transcript. The precise mode of action of r is unknown; it has been proposed that there is a r recognition site in the RNA, and that termination occurs at a relatively fixed distance downstream of this recognition site [Book ref. 188, pp. 155–178]. The NusA protein also appears to play some role in termination. [Review of transcription termination: Book ref. 60, pp. 123–161.] The initial product of transcription (the primary transcript) may undergo extensive processing and/or modification to give the mature RNA product: see e.g. entries for mRNA, rRNA and tRNA. Initiation and termination of transcription are important control points for gene expression: see e.g. ANTITERMINATION, CATABOLITE REPRESSION, OPERON. (See also POLAR MUTATION.) transcription antitermination In certain Gram-positive bacteria (e.g. Bacillus subtilis): a control mechanism in which genes whose products are involved in the synthesis of amino acids (and in linking amino acids to tRNAs) are switched on when limiting amounts of those amino acids give rise to uncharged tRNAs. It appears that an uncharged tRNA interacts with the leader region of the gene’s mRNA, causing reversal of a transcription terminator structure (formed when the cell has adequate amounts of the amino acid) to an antiterminator structure, thus enabling synthesis of the amino acid. [tRNAdirected transcription antitermination: Mol. Microbiol. (1994) 13 381–387.] transcription initiation factors See RNA POLYMERASE. transcription-mediated amplification See TMA. transcriptional coupling Coupling between closely spaced promoters which results from divergent transcription from the promoters and the consequent transcription-dependent increase in negative superhelicity in the region between the active RNA polymerases; such local accumulation of negative superhelicity may activate or repress a promoter, or it may have little or no effect, depending on the intrinsic properties of the given promoter. [Possible role of transcriptional coupling in the ilv regulon of Escherichia coli: Mol. Microbiol. (2001) 39 1109–1115.] transcytosis In certain Opa+ strains of Neisseria: translocation through a layer of (mammalian) epithelial cells without disruption of the eukaryotic cell–cell junctions; transcytosis involves an initial phase in which the bacteria bind to specific receptors on the host cells and are then engulfed by the host cells [TIM (1998) 6 489–495]. (See also PARACYTOSIS.) transductant See TRANSDUCTION. transduction The virus-mediated transfer of host DNA (chromosomal or plasmid) from one host cell (the donor ) to another (the recipient). Transduction was first observed in bacteriophage/bacterium systems, but has since also been found to be mediated by certain viruses infecting eukaryotic cells (see RETROVIRIDAE). The account below concerns only phage/bacterium systems. Essentially, when a phage replicates in a (donor) cell, a few progeny virions encapsidate pieces of host DNA instead of – or in addition to – phage DNA; these virions can adsorb to a new host cell and introduce their DNA in the usual way. There are two basic types of phage-mediated transduction. (a) Generalized transduction: any of a wide range of donor genes may be transduced, and the transducing phage particles contain only donor DNA. In some systems any of the host genes has a more or less equal chance of being transduced, but in

other systems some genes are transferred at higher frequencies than others. For example, in the BACTERIOPHAGE P22/Salmonella system, certain regions of the host chromosome resemble the P22 pac site, and packaging of chromosomal DNA may be initiated at and proceed from these sites [MGG (1982) 187 516–518]; thus, the probability of a given gene being transduced depends on its distance from a pac-like site. (Certain ‘highfrequency transduction’ (HT) mutants of P22 have been shown to be defective in pac recognition [JMB (1982) 154 551–563].) The fate of the transduced DNA in the recipient cell (now called a transductant) depends on various factors. If the DNA is a complete replicon (e.g. a plasmid) it may be stably inherited by the transductant. If the DNA is a fragment of a chromosome or plasmid, it may undergo one of three possible fates. (i) It may be completely degraded by the recipient cell’s RESTRICTION ENDONUCLEASE system. (ii) It may undergo RECOMBINATION with a homologous region of the recipient’s chromosome (or plasmid), so that at least some of the genes it carries can be stably inherited (complete transduction). (iii) It may persist in the cell in a stable but non-replicating form (abortive transduction). (The transduced DNA in an abortive transductant may exist as a circular DNA–protein complex [Virol. (1980) 106 30–40].) Any donor genes present (and linked to promoters) may be expressed, and (if they are dominant alleles) the transductant may express the donor phenotype in respect of these genes. However, when an abortive transductant divides, only one of the daughter cells will receive the donor fragment; the other may nevertheless receive sufficient donorgene products to permit expression of the donor phenotype for one or a few generations. Such abortive transduction is normally manifest by the formation of minute (often microscopic) colonies on medium selective for transductants; only one cell in the colony actually contains donor DNA. The transduction of one particular donor gene is a rare event (e.g. 10−7 –10−5 , depending e.g. on phage). If two or more genes are transduced together (cotransduction) they are assumed to occur on the same fragment of DNA and are thus closely linked in the donor; generalized transduction has thus been used in the detailed mapping of donor chromosomes, distances between markers being estimated by determining their contransduction frequencies. (b) Specialized (restricted ) transduction is mediated only by temperate phages which integrate into the host chromosome (see LYSOGENY); only bacterial genes immediately adjacent to the prophage can be transduced, and the transduced DNA is covalently linked to some or all of the phage genes. For example, when a population of Escherichia coli cells lysogenized by BACTERIOPHAGE l is induced, a small proportion of the progeny virions may carry either gal or bio host genes – often at the expense of certain phage genes at the opposite end of the prophage (virion component genes in gal-containing particles, control genes in bio-containing particles); such virions (specialized transducing particles, STPs) arise as a result of rare aberrant excision events in which recombination occurs between sites other than the hybrid att sites (attR and attL). (A lysate from an induced lysogen will normally contain a heterogeneous population of STPs resulting from different aberrant excision events in different cells.) An STP can infect a recipient cell and introduce its DNA into the cell; however, if it lacks phage genes essential for replication (i.e., if it is defective) it will require the presence of a (non-defective) helper phage in order to produce progeny STPs. (cf. RETROVIRIDAE.) A lysate obtained by induction of a lysogen contains only a small (and mixed) population of STPs (e.g. one STP per 106 787

transductional shortening wild-type particles); consequently, when the lysate is used to infect a culture of recipient cells only a few of the cells will be infected by an STP. Such lysates are therefore termed lowfrequency transducing (LFT) lysates. If e.g. a gal − recipient culture is infected with an LFT lysate derived from a gal + donor population, a few recipients will become gal − /lgal + (merodiploid heterogenotes). In some of these cells homologous recombination may occur between the gal − and gal + regions to result in a stable, non-lysogenic gal + transductant (‘replacement transduction’). Alternatively, the DNA of the STP may integrate, intact, into the host chromosome by homologous recombination, producing a lysogenic heterogenote (‘addition transduction’). (Owing to the manner of its formation, an STP will normally contain a hybrid attR or attL site instead of the usual attP, and so integrates at attB only with low efficiency.) However, since non-transducing (wild-type) phage particles are present in great excess in an LFT lysate, at high multiplicities of infection a recipient is likely to be simultaneously infected with both wild-type and transducing phages. In this case both phage genomes can integrate into the recipient’s chromosome to form a double lysogen; this probably occurs by normal site-specific integration of the wild-type genome, followed by homologous recombination between it and the defective phage genome. If the double lysogen is subsequently induced, both phages will replicate (the wild-type phage supplying the missing functions of the defective STP); the resulting lysate may thus contain approximately equal numbers of l and lgal + particles. Furthermore, the population of STPs will be homogeneous, unlike that in an LFT lysate. Such a lysate can be used to infect another population of cells, and the gal + genes will be transduced with high frequency; the lysate is thus termed a highfrequency transducing (HFT) lysate. Rarely, the genome of a wild-type l integrates at sites other than attB in the host chromosome, and STPs from such lysogens will carry genes other than gal or bio. (See also MINI-MU.) transductional shortening The phenomenon observed in the TRANSDUCTION of a large plasmid: the transduced plasmid is smaller than the original donor plasmid, probably because the phage particles encapsidate deletion mutants of the plasmid (which arise spontaneously at low frequencies). transfection Originally, the introduction of viral nucleic acid into an intracellular environment and the subsequent formation of normal virions. Currently, the term is used for any in vitro procedure in which nucleic acid is introduced into cells in order to modify those cells genetically or to carry out intracellular experimentation. Transfection is also used to refer to the introduction of proteins or peptides into cells. transfer DNA synthesis Syn. DCDS: see CONJUGATION (1b)(i). transfer operon (tra operon) In a CONJUGATIVE PLASMID: an OPERON containing those genes which specify functions necessary for CONJUGATION (sense 1b). (cf. SEX FACTOR sense 2.) In some conjugative plasmids (see e.g. F PLASMID) the genes of the transfer operon encode e.g. PILI, certain proteins involved in DNA mobilization, and proteins involved in SURFACE EXCLUSION. Some conjugative plasmids (e.g. the F plasmid) are DEREPRESSED for conjugal transfer, but many or most are repressed. (See also FINOP SYSTEM.) transfer RNA See TRNA. transferases ENZYMES (EC class 2) which catalyse the transfer of a group from one molecule to another. Subclasses are recognized and numbered according to the nature of the group transferred

(e.g., subclass 1: one-carbon groups such as methyl, formyl, hydroxymethyl). transferosome See CONJUGATION (1b)(i). transferrin A SIDEROPHILIN which occurs in vertebrate plasma; its main function is to transport iron into cells. The iron–transferrin complex binds to a cell-surface receptor and is internalized via a coated vesicle (see PINOCYTOSIS); the iron is subsequently released, within the cell, and may be stored as an iron– FERRITIN complex. Although iron is tightly bound by transferrin it can be removed e.g. by certain bacteria or their products: see IRON. Interestingly, the intraerythrocytic stage of Plasmodium falciparum appears to obtain iron from iron–transferrin complexes by synthesizing transferrin receptors that become localized in the cell surface of the infected erythrocyte [Nature (1986) 324 388–391]. transformant A cell or organism which has undergone genetic TRANSFORMATION. transformation (1) (genetics) A process in which exogenous DNA is taken up by a (recipient) cell, sphaeroplast or protoplast, in which it may be incorporated into the chromosome (or e.g. into a plasmid) by homologous RECOMBINATION or converted into an autonomous replicon. The DNA (transforming or donor DNA) may be e.g. a fragment of chromosomal DNA from a related strain, a plasmid, or a viral genome (see TRANSFECTION). Transformation can occur under natural conditions in some bacteria (e.g. Bacillus, Haemophilus, Neisseria and Streptococcus spp), but in many bacteria (including e.g. Escherichia coli ) and in certain eukaryotic microorganisms it can occur only in cells ‘permeabilized’ to DNA by artificial methods. It has been suggested that transformation (among other mechanisms) may contribute to the spread of antibiotic resistance in certain pathogenic bacteria [Science (1994) 264 375–382]. Natural bacterial transformation systems. Cells which are able to take up DNA are said to display competence. Competence is apparently constitutive in some species – e.g. Neisseria gonorrhoeae (in which it is reported to occur only in fimbriated cells [JGM (1984) 130 3165–3173]). However, in other species competence is a transient phenomenon that is dependent on certain factors – such as nutritional status and/or the phase of growth (in batch cultures). In Haemophilus influenzae, for example, competence is induced by growth-inhibiting conditions; in this species it is promoted by high levels of intracellular cAMP (cyclic AMP). In both Bacillus subtilis and Streptococcus pneumoniae competence is affected e.g. by the population density of the bacteria – an example of QUORUM SENSING. For example, when B. subtilis grows to a high density of cells, a secreted pheromone (designated ComX) accumulates in the extracellular environment; at an appropriate concentration, ComX activates a TWO-COMPONENT REGULATORY SYSTEM which, in turn, leads to the activation of certain genes (including comS) whose function is needed for the establishment of competence. In S. pneumoniae, competence has also been associated with the transmembrane transport of calcium [JB (1994) 176 1992–1996]. [Competence in transformation: TIG (1996) 12 150–155.] To be effective in transformation, a fragment of chromosomal DNA must be double-stranded and larger than a certain minimum size – which depends on recipient. The DNA binds to the surface of a competent cell; initially binding is reversible and dependent on the concentration of the donor DNA, but subsequently a limited number of DNA molecules become irreversibly bound to specific cell-surface receptor sites. In S. pneumoniae and B. subtilis binding is non-specific with respect to the DNA, DNA from other species being bound 788

transfusion-transmitted infection may promote binding of DNA to the cell and increase the permeability of the cell envelope. In one scheme, calcium chloride solution (approx. 50 mM, 0.2 ml) containing 108 –109 washed, mid-log-phase cells of E. coli is chilled on ice, and a DNA suspension (10 µl) is added to give a final concentration of DNA of approx. 0.2 µg/ml; after further chilling at 0° C (15–30 minutes), the suspension is heat-shocked (42° C/1.5–2 minutes) and allowed to recover – e.g. returned to ice and then incubated in Luria–Bertani broth (1 ml) at 37° C for 1 hour. The acquisition of competence by E. coli in ice-cold solutions of calcium is associated with the presence of a high concentration of poly-b-hydroxybutyrate/calcium polyphosphate complexes in the cytoplasmic membrane. It has been suggested that these complexes may form transmembrane channels which facilitate DNA transport, and that divalent cations may act as links between DNA and phosphate at the mouth of such channels [JB (1995) 177 486–490]. Small, circular plasmids tend to transform more readily than do larger ones. In wild-type E. coli, linear dsDNA transforms poorly (if at all) as it is degraded by the RecBC enzyme; linear dsDNA can transform some recBC mutants which lack a functional enzyme. High-efficiency transformation of E. coli (and various other bacteria) with plasmids may be achieved by ELECTROPORATION. Protoplasts from Gram-positive bacteria can be induced to take up DNA by treatment with POLYETHYLENE GLYCOL (PEG); viable cells can then be regenerated from the transformed protoplasts (and from certain types of sphaeroplast). (See also PROTOPLAST FUSION.) PERMEAPLASTS have been used for the transformation of certain cyanobacteria. [DNA uptake by ‘Anacystis nidulans’: MGG (1986) 204 243–248.] In artificially competent cells, sphaeroplasts and protoplasts, DNA appears to be taken up intact. [Methods for bacterial transformation by plasmid DNA: Book ref. 177, pp. 61–95.] Certain fungi can be transformed artificially. In e.g. Saccharomyces cerevisiae, one method involves mixing sphaeroplasts (prepared e.g. with Zymolyase) with the DNA in the presence of Ca2+ , and then adding PEG; in another method, whole cells are treated with alkali metal ions (usually lithium ions) and PEG, a method which is simpler but less efficient. [Transformation in fungi: Book ref. 179, pp. 161–195 (yeast) and pp. 259–278 (Aspergillus); Book ref. 178, pp. 468–472 (Cephalosporium acremonium).] Certain unicellular green algae can also be transformed: e.g. Chlamydomonas reinhardtii has been transformed with yeast DNA [Nature (1982) 296 70–72]. (2) (of cells in tissue culture) See TISSUE CULTURE. (3) (of lymphocytes) See BLAST TRANSFORMATION. transforming DNA (‘transforming principle’) See TRANSFORMATION (1). transfusion-transmitted infection Any infectious disease which can be transmitted via a transfusion of blood or blood-related products. Transfusion-transmissible agents include certain bacteria (e.g. Treponema pallidum), protozoa (e.g. Plasmodium spp) and viruses (e.g. hepatitis viruses B and C, human immunodeficiency virus (HIV) and, more recently, TT VIRUS). (See also CREUTZFELDT–JAKOB DISEASE.) [Transfusion-associated hepatitis G virus infection: NEJM (1997) 336 747–754. Transfusion-transmitted malaria in the USA: NEJM (2001) 344 1973–1978.] Other risks from transfused blood (apart from infection) include the possible presence of pro-inflammatory cytokines

as readily as DNA from the same species. By contrast, in Haemophilus and Neisseria spp DNA binding is sequencespecific; H. influenzae takes up only dsDNA containing a ‘DNA uptake site’, a sequence (5′ -A–A–G–T–G–C–G–G–T–C–A3′ [Gene (1980) 11 311–318]) which occurs frequently in the genomes of H. influenzae and H. parainfluenzae but much less so in DNA from other organisms. In B. subtilis and S. pneumoniae the bound DNA is cleaved by an envelope-associated endonuclease. Subsequently, one strand of a fragment is internalized while its complement is degraded. It has been suggested that binding and uptake are achieved by a membrane-bound nuclease-containing protein complex, the nuclease processively degrading one strand of the DNA, thereby (possibly) driving the other through a pore in the membrane formed by other components of the complex. Within the recipient cell, the single-stranded fragment rapidly associates with cellular proteins to form a presynaptic eclipse complex ; this probably protects the DNA from degradation. Synapsis between the donor (chromosomal) DNA and a homologous region of the recipient’s chromosome rapidly ensues, and a single-stranded fragment of recipient DNA is effectively excised and replaced by the donor ssDNA to form a region of hybrid DNA; this could occur e.g. by invasion of the recipient duplex by the donor strand followed by ‘strand assimilation’ (cf. RECA PROTEIN). In Haemophilus influenzae and H. parainfluenzae a different type of uptake mechanism apparently occurs [PNAS (1982) 79 6350–6374], and dsDNA enters the recipient cell; however, recombination apparently still involves the pairing of a single donor strand with a complementary region of the resident DNA. Resolution of the heteroduplex region may occur by separation of the strands during a subsequent round of semiconservative DNA synthesis, yielding some progeny resembling the donor, others the recipient, with respect to markers in this region. Alternatively, one of the strands may be corrected by a MISMATCH REPAIR system (gene conversion: cf. RECOMBINATION) to yield a homoduplex and hence a single type of progeny. In S. pneumoniae (but not in B. subtilis) some singlesite mutations in the donor DNA are integrated into the recipient’s chromosome more efficiently than others; it seems that this organism encodes a mismatch repair system (hex genes) which has different affinities for different mismatched base pairs, eliminating low-efficiency (LE) markers more efficiently than high-efficiency (HE) markers. (In hex − mutants all single-site mutations are integrated with the same high efficiency.) [Hex system in S. pneumoniae: MR (1986) 50 133–165.] Plasmid DNA (ccc, ds) may also be taken up by competent cells; however, in natural systems transformation with plasmid monomers generally occurs only at very low frequencies, if at all, whereas plasmid oligomers (trimers or larger) can transform at high frequencies. Apparently the ccc dsDNA binds to the surface of a competent cell and undergoes cleavage and some degradation, and single strands enter the cell with the same polarity; if the plasmid is an oligomer, enough complementary ssDNA can eventually enter the cell to allow annealing and circularization and hence, with repair synthesis and ligation, regeneration of a plasmid monomer. Artificial transformation systems. Non-competent cells of e.g. Bacillus or Streptococcus, or cells of those bacteria (e.g. E. coli) which cannot undergo transformation under natural conditions, may be induced to take up transforming DNA by various procedures involving laboratory-induced competence. For example, treatment of E. coli and other Gram-negative bacteria with high (millimolar) concentrations of calcium chloride, often in association with heat shock, induces artificial competence; calcium ions 789

transgenesis translational enhancer See DOWNSTREAM BOX. translational feedback regulation See e.g. RIBOSOME (biogenesis). translational frame-shifting A control mechanism in which the expression of certain genes is regulated during the translocation stage of PROTEIN SYNTHESIS. In this process, a specific sequence of nucleotides in the transcript acts as a signal that causes the ribosome to ‘slip’ along the mRNA; such a movement usually involves a ‘+1 slip’ (i.e. a 1-nucleotide shift in the direction of translation) or a ‘−1 slip’ (a 1-nucleotide shift in the opposite direction). Such a shift necessarily affects all subsequent codons. [Review: Mol. Microbiol. (1994) 11 3–8.] translational operator See e.g. RIBOSOME. translesion synthesis See SOS SYSTEM. translocase Syn. translocon: see PROTEIN SECRETION (type II systems). translocation (1) See PROTEIN SYNTHESIS. (2) Passage of viable bacteria across the epithelial barrier from the gut lumen [review: BCG (2003) 17 397–425]. translocon See PROTEIN SECRETION. transmissible disease (1) Any disease which can be transmitted from one individual to another, or to a fetus, by any means, including experimental infection; ‘transmissible disease’ is therefore broader (more inclusive) than INFECTIOUS DISEASE. (2) Loosely, an infectious disease. transmissible gastroenteritis (in pigs) An acute, typically nonfebrile PIG DISEASE, characterized by diarrhoea and dehydration, which is often fatal in very young pigs; the causal agent is a coronavirus. The mode of transmission is uncertain. Incubation period: ca. 1–2 days. The virus replicates in distal regions of the villi, causing malabsorption and osmotically induced, typically yellowish-green diarrhoea. transmissible hypovirulence See HYPOVIRULENCE. transmissible mink encephalopathy A disease of mink which is probably a form of SCRAPIE; it appears to have arisen as a result of feeding farmed mink with scrapie-infected sheep meat. The disease can be transmitted experimentally to various other animals (but not to mice); in monkeys, infection results in a disease resembling experimental CREUTZFELDT–JAKOB DISEASE. transmissible spongiform encephalopathies (TSEs) Fatal diseases of the nervous system characterized by spongiform degeneration of the brain without inflammation or specific immune response; in each disease the causal agent is a PRION (q.v.). Unique features of TSEs include: (i) a novel mechanism of pathogenesis, (ii) manifestation in sporadic, inherited and transmitted forms, and (iii) (in contrast to e.g. Alzheimer’s disease) manifestation in a range of histopathological patterns. Human TSEs include CREUTZFELDT–JAKOB DISEASE, GERST¨ MANN–STRAUSSLER–SCHEINKER SYNDROME (GSS syndrome) and KURU (all previously referred to as ‘transmissible viral dementias’), and fatal familial insomnia (FFI; [NEJM (1992) 326 444–449]). FFI and GSS syndrome are both inherited diseases. TSEs acquired by infection include kuru and (apparently) nvCJD (as well as the iatrogenic forms transmitted via medical/surgical treatment). Where infection involves ingestion of prion-contaminated food, it is believed that conversion of PrP to the prion form occurs initially within tissues of the gastrointestinal tract, and that such conversion continues to occur progressively in the lymphatic and/or peripheral nervous systems until it reaches the central nervous system. [Book ref. 215.] The deposition of prions, in itself, may not be sufficient to cause neuropathy [Nature (1996) 379 339–343], suggesting that the development of disease may involve some kind of interaction between prions and the host’s tissues.

released from white blood cells during prolonged storage [e.g. Transfusion (1996) 36 960–965]. Avoidance of transfusion-transmitted infection is promoted e.g. by careful screening of donors and by appropriate tests on donated blood for specific infectious agents. Even so, infections still occur through transfusion. (Autologous blood transfusion involves re-infusion of the patient’s own blood taken prior to anticipated requirement; one risk is that contamination may occur during donation, storage or use.) For viral diseases, a major risk is that blood may be donated at a time when the donor has been recently infected with a given agent, is able to transmit that agent via blood, but has not yet become seropositive for the agent (i.e. the agent is still undetectable serologically). The period between initial infectivity and development of seropositivity (known as a diagnostic window ) varies from one virus to another but is generally of the order of weeks/months. (In this context it is noteworthy that, normally, donor blood can be stored for a maximum of 35 days in the UK and 42 days in the USA.) To reduce the risk from window-phase blood, PCR-based tests have been used to detect the nucleic acid of hepatitis B and C viruses and the HIV-1 virus [Lancet (1999) 353 359–363]; nevertheless, transmission of hepatitis C virus via a blood donation negative in nucleic-acid-amplification tests has been reported [Lancet (2000) 355 41–42]. Other risk factors associated with transfused blood include the possibility that tests for a given agent may be insufficiently sensitive or may not detect genetically variant forms of an infectious agent. Additionally, human (laboratory) error, though rare, is always a possibility. [Genome detection versus serology in blood screening for microbial agents: BCH (2000) 13 (4) chapter 8.] transgenesis Incorporation of alien DNA, heritably, into living organisms by in vitro methods. [Book ref. 204.] transhydrogenase Nicotinamide nucleotide transhydrogenase (EC 1.6.1.1): an enzyme which catalyses the (reversible) reduction of NADP+ by NADH. AB-transhydrogenases are membrane-bound enzymes which occur e.g. in some bacteria and in mammalian mitochondria; BB-transhydrogenases are soluble flavoprotein enzymes found only in certain bacteria. Transhydrogenation of NADP+ by AB-transhydrogenases appears to be regulated by pmf (see CHEMIOSMOSIS); transhydrogenation by BB-transhydrogenases is promoted e.g. by 2′ -AMP and Ca2+ . transition mutation A type of POINT MUTATION in which one purine nucleotide is replaced by another, or one pyrimidine nucleotide is replaced by another. (cf. TRANSVERSION MUTATION.) transition state (sporulation) See ENDOSPORE (sense 1). transketolase See e.g. CALVIN CYCLE and Appendix I(b). translation See PROTEIN SYNTHESIS. translational attenuation A control mechanism in which the expression of certain genes is regulated by inhibition of their translation under given conditions. For example, in certain Gram-positive bacteria the cat gene (encoding chloramphenicol acetyltransferase) is induced by CHLORAMPHENICOL but normally remains unexpressed in the absence of this antibiotic. In the absence of chloramphenicol, the cat gene is transcribed but not translated; this is because the ribosome-binding site of the coding sequence is inaccessible owing to an inhibitory secondary structure in the mRNA formed by base-pairing between certain ribonucleotides. The presence of chloramphenicol inhibits development of the secondary structure, thus relieving repression of translation. (This mechanism operates with levels of chloramphenicol below those which inhibit protein synthesis.) 790

transport systems Prions can be distinguished from the normal form of the protein by their ability to bind to plasminogen (a precursor of FIBRINOLYSIN), and this may be used as a basis for the development of a diagnostic test [Nature (2000) 408 479–483]. In animals, the TSEs include BOVINE SPONGIFORM ENCEPHALOPATHY (BSE; ‘mad cow disease’), chronic wasting disease of elk and mule-deer, SCRAPIE, and TRANSMISSIBLE MINK ENCEPHALOPATHY. Transmission of TSEs across species barriers has been demonstrated experimentally in a number of cases (e.g. sheep → mice; bovines → monkeys). transmissible viral dementias See TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES. transmission-blocking vaccine See e.g. PLASMODIUM. transmission factor (plant virol.) See NON-CIRCULATIVE TRANSMISSION. transovarial transmission Transmission of a parasite from a host (or vector) to its offspring via the egg. (See e.g. BLACKHEAD and PULLORUM DISEASE; cf. VERTICAL TRANSMISSION.) transpeptidation (in protein synthesis) See PROTEIN SYNTHESIS. transport medium Any medium used specifically for the transportation and/or temporary storage of material (e.g. swabs) from which the isolation of particular organism(s) is subsequently to be attempted. The purpose of such a medium is to maintain the viability and/or infectivity of the organism(s) during the delay between collection and culture of the specimen. An effective transport medium is necessary e.g. for anaerobes (which may be killed by short or prolonged exposure to oxygen), for delicate organisms (e.g. Neisseria gonorrhoeae), and for certain viruses. The commonly used transport media are nonnutrient media which include STUART’S TRANSPORT MEDIUM and its modifications, e.g. Cary–Blair transport medium and Amies transport medium – the latter incorporating charcoal. (Charcoalcontaining media obviate the need for collecting specimens on charcoal-impregnated swabs – the charcoal, in each case, serving to adsorb inhibitory substances in the medium and/or specimen.) Some transport media have been devised for particular organisms: see e.g. MONSUR TRANSPORT MEDIUM. For many types of virus, HANKS’ BSS supplemented with protein (e.g. 0.5–2.0% bovine albumin) may be an effective transport medium; in such a medium some viruses can be rapidly frozen and stored at ca. −70° C. transport systems Systems which permit the uptake or efflux of molecules or ions across membranes (e.g. ENERGY-TRANSDUCING MEMBRANES or the OUTER MEMBRANE in Gram-negative bacteria) – which are otherwise impermeable; the term ‘transport’ is used in a way which excludes transmembrane translocations concerned exclusively with energy conversion. Some transport systems are specific for a particular substrate (or a few substrates) while others may be used for a range of substrates. Transport systems involved in the acquisition of essential component(s) are of course vital for the survival/growth of an organism. Such systems include e.g. the various IRONuptake mechanisms in a range of organisms. Again, the inability of parasitic protozoa to synthesize their own purine nucleotides de novo means that these organisms must import pre-formed purines from their hosts; such uptake involves the operation of nucleoside transport systems which have been identified in various parasitic protozoa (including Leishmania donovani, Plasmodium falciparum, Toxoplasma gondii and Trypanosoma brucei) [see e.g. TIP (2001) 17 142–145]. Typically, transport requires energy (= active transport ). Energy-independent transport may involve simple diffusion – for

example, uptake of small molecules or certain types of ion through a PORIN – or FACILITATED DIFFUSION (see also glycerol facilitator in MIP CHANNEL). In some cases transport and energy conversion are linked: see e.g. END-PRODUCT EFFLUX. Energy-dependent transport may permit a cell or organelle to accumulate a substrate against a concentration gradient; this is necessary e.g. when a required molecule or ion occurs in low concentrations in the external environment. Such transport includes the following categories: (a) Group translocation. In this form of transport the transmembrane translocation of substrate is obligatorily linked with chemical modification of that substrate. Transport systems of this type are commonly used e.g. for the uptake of sugars by bacteria: see PTS. (b) ATP hydrolysis-dependent transport. The hydrolysis of ATP provides energy for various types of transport. For example, in Escherichia coli, ATP hydrolysis is needed for osmoregulatory uptake of potassium ions at a particular membrane ATPASE (potassium pump). (See also ION TRANSPORT (b) and (d); TWOCOMPONENT REGULATORY SYSTEM.) Uptake of IRON by the E. coli SIDEROPHORE enterochelin involves initial binding of the iron–enterochelin complex by the FEPA PROTEIN. FepA is energized via the TONB PROTEIN (q.v.), and the iron–siderophore complex, released from FepA, passes through a system of proteins in the cytoplasmic membrane – transfer of the complex to the cytoplasm depending on ATP hydrolysis at a specific ATPase (FepC protein) in the cytoplasmic membrane. ATP hydrolysis is also an essential feature of a large family of transport systems known as ABC TRANSPORTERS (q.v.) which include both importers and exporters. Certain types of bacterial PROTEIN SECRETION involve energy derived from ATP hydrolysis. (c) Pmf-dependent transport. Proton motive force (see CHEMIOSMOSIS) can be used, directly, for the transport of certain charged and uncharged species. Examples include the uptake of calcium ions by mitochondria (see ION TRANSPORT), and the proton–lactose symport system for lactose uptake in Escherichia coli. Such transport is inhibited by PROTON TRANSLOCATORS. The uptake of vitamin B12 across the outer membrane in E. coli is pmf-dependent [see JB (1993) 175 3146–3150]. As well as acting as a source of energy for transport, pmf can also regulate other transport systems. For example, by controlling the redox state of certain redox-sensitive membrane carrier proteins, pmf (as well as the redox potential of the environment) can control the transport of e.g. glucose by the PTS [AvL (1984) 50 545–555]. (d) Smf-dependent transport. See SODIUM MOTIVE FORCE and ION TRANSPORT. Transport in the control of metabolism. The transport of a given substrate may be the rate-limiting step in the metabolism of that substrate; hence, the transport process itself may constitute an important control mechanism. According to the particular system involved, transport may be dependent on e.g. the level of pmf, the availability of a given ion species (for ion–substrate symport) or (as in the PTS) the availability of ‘high-energy’ compounds. In some cases, transport is reported to require the operation of the electron transport chain, i.e. to depend on electron flow rather than on pmf [AvL (1984) 50 545–555]. Effect of transport on yield coefficient. Differences in the YIELD COEFFICIENT of a given organism grown on different substrates may be attributed, at least partly, to differences in the energy costs of substrate transport. For example, in E. coli the transport 791

transporter of lactose by proton–lactose symport has been calculated to cost ca. 0.5 ATP per molecule transported, while maltose transport via a binding protein-dependent mechanism has been calculated to cost ca. 1.0–1.2 ATP per molecule transported [JB (1985) 163 1237–1242]. Transport in other cell functions. The above account refers primarily to transport involved in metabolism, secretion and osmoregulation. Transport is also required for e.g. PTSdependent CHEMOTAXIS and for certain aspects of pathogenicity (see type III systems in PROTEIN SECRETION); it also appears to be involved in GLIDING MOTILITY in certain cyanobacteria [see e.g. JB (2000) 182 1191–1199 (1195–1196)]. transporter See PERMEASE. transposable element (TE; ‘jumping gene’) A discrete DNA segment, within a larger DNA replicon, which can (actually or effectively) translocate to another (target) site in the same replicon, to a target site in another replicon in the same cell, or (see CONJUGATIVE TRANSPOSITION) to a target site in another cell; such translocation (termed transposition) does not require extensive DNA sequence homology between the TE and its target site. The following account refers to ‘classical’ transposable elements, i.e. TEs other than conjugative transposons. TEs are normal components of e.g. chromosomes, plasmids and phage genomes. They are found in prokaryotes (see INSERTION SEQUENCE and TRANSPOSON) and in eukaryotes – including yeasts (see e.g. TY ELEMENT), protozoa, Drosophila and higher plants. (See also INTRON HOMING.) By convention, the presence of a TE in a given replicon is indicated by a double colon; for example, the presence of transposon Tn3 within a phage l genome is designated l::Tn3. Different TEs employ different mechanisms for transposition. In bacteria, some TEs transpose by a rec-independent ‘replicative’ process, while others employ a non-replicative (‘simple’) mechanism – terms illustrated in the figure. (See also entries for Tn10 and Tn5.) Some TEs can apparently employ different transposition mechanisms under different conditions: see e.g. BACTERIOPHAGE MU. In eukaryotes, certain TEs appear to transpose via an RNA intermediate: see TY ELEMENT. Transposition is normally a rare event, the actual frequency depending e.g. on the TE and on the physiological state of the cell (see e.g. entry for Tn501 ). Functions necessary for transposition are usually encoded by the TE itself, although certain host cell functions may also be required – for example, in Escherichia coli, GYRASE has been implicated in the transposition of e.g. Tn5 [Cell (1982) 30 9–18]. Most TEs have a reading frame for at least one protein (e.g. a TRANSPOSASE), and each TE includes terminal INVERTED REPEAT sequences which apparently permit recognition of the TE by its transposase. Target-site specificity is an intrinsic property of a TE. Some TEs (see entry for Tn7) are highly site-specific, while others appear to insert almost randomly; for example, Tn3 and IS1 show a preference for targets in (easily denaturable) AT-rich regions (cf. BACTERIOPHAGE MU), while IS5 inserts only at sites containing the sequence C(T/A)A(G/A). Nevertheless, even when insertion seems random, some kind of selective process is likely to be involved [ARB (1997) 66 437–474]. Studies on the transposition of IS903 into a large (55 kb) plasmid indicate that, while insertion can occur at many different sites, there are certain preferred regions into which IS903 will insert more than once on different occasions [JB (1998) 180 3039–3048].

Certain targets, termed ‘hot-spots’, are especially prone to insertion by particular TEs; for example, hot-spots for Tn3 insertion have been found to contain regions of homology with the Tn3 termini – although hot-spots for Tn10 insertion (see entry Tn10 ) bear no obvious relationship to the Tn10 termini. Insertion of a TE at a target site results in the formation of direct repeats flanking the inserted TE; this is illustrated in the figure – which shows a scheme for the insertion of a TE by both ‘simple’ and ‘replicative’ mechanisms. The length of the target duplication is usually specific for the TE involved – for example, 5 bp for Tn3 and 9 bp for Tn10 (cf. IS1 ). The transposition of some TEs (e.g. bacteriophage Mu, members of the Tn3 /gd family) is regulated by a trans-acting repressor (cf. Tn5 ); when a TE of this type enters a ‘naive’ host (i.e. a cell lacking a TE of the same type), transposition functions are expressed at a high level until repression of the TE has been established. (See also TRANSPOSITION IMMUNITY and MULTICOPY INHIBITION.) The transposition of e.g. Tn10 from a chromosomal location in Escherichia coli tends to be linked to the cell cycle; this is because Dam methylation inhibits transcription of the Tn10 transposase gene, and such inhibition is transiently relieved during chromosomal replication (immediately after the replication fork has passed the transposase gene but prior to Dam methylation of the gene). TEs may be more or less ‘host-specific’; for example, IS1 appears to be limited mainly to strains of Escherichia coli K12. [TEs in prokaryotes (review): ARB (1985) 54 863–896.] The consequences of insertion of a TE at a new site depend on the TE and on the nature of the target site etc. If the insertion site is in a structural gene, an insertion mutation will result. If insertion occurs in an OPERON, strong polar effects may occur because TEs carry transcriptional and/or translational stop signals which prevent expression of all genes downstream of the insertion site. Insertion of a TE may also activate an operon – for example, the TE may carry a functional promoter, or may insert into, and inactivate, a sequence involved in the negative control of the operon. Precise excision of a TE from a site of insertion (an event that occurs at low frequency) leads to reversion of the corresponding mutation; however, imprecise excision (e.g. with deletion of adjacent host DNA) can also occur. See also TRANSPOSON MUTAGENESIS. TEs can also mediate a wide range of DNA rearrangements, including deletions and inversions of adjacent host DNA, formation and resolution of COINTEGRATES, gene fusion and amplification etc. These processes may be mediated by the mechanisms responsible for transposition per se; however, in some cases they may occur by transposition of a TE to another site in the same (or a different) replicon followed by recAdependent recombination between the homologous sites thus created. (See also entries for individual TEs under ‘IS’ and ‘Tn’.) transposase An enzyme which is responsible for at least part of the process of transposition of a TRANSPOSABLE ELEMENT; a transposase (or a component of it) is usually encoded by the TE itself and is specific for that TE or for TEs with closely related terminal inverted repeats. (See e.g. Tn3 ; cf. IS101 and Tn951.) transposition See TRANSPOSABLE ELEMENT. transposition (conjugative) See CONJUGATIVE TRANSPOSITION. transposition immunity A phenomenon in which a replicon containing a copy of Tn3 (or a Tn3-related transposon) is immune to the insertion of a second copy of the same transposon; the frequency of transposition of the transposon to other replicons in the same cell is unaffected. In the case of Tn3 the immunity 792

donor

target

(a)

3′ 3′

(b)

(d)

(c)

(e)

TRANSPOSABLE ELEMENT: a (diagrammatic) scheme for a transposon undergoing ‘simple’ and ‘replicative’ transposition. (a) Two circular double-stranded DNA molecules. On the left, the donor molecule includes a transposon (dashed lines) – either side of which is an old ‘target’ site ( ); the donor’s target site was duplicated when the transposon was originally inserted into the donor molecule (see later). ) where the transposon will be inserted. On the right, the molecule which will receive the transposon has a single target site ( (b) An enzyme (a transposase – not shown) mediates at least the initial stages of transposition. A staggered break has been made at the target site. In the donor molecule, a nick has been made in each strand of the transposon (at opposite ends), and the free ends have been ligated to the target molecule, as shown. In ‘simple’ transposition (which occurs e.g. in transposon Tn10) the next (and final) stage is shown at (c). (c) The result of ‘simple’ transposition. DNA synthesis has occurred from each free 3′ end in the target molecule, using the (single-stranded) ). The remaining strand-ends of the transposon have been target site as template, to form the complementary strand of each target site ( nicked and ligated as shown. Note that the target molecule’s target site has been duplicated – compare with the donor molecule at (a). The rest of the donor molecule may be non-viable (‘donor suicide’). (d) ‘Replicative’ transposition (which occurs e.g. in Tn3) involves stages (b), (d) and (e). At (d), new DNA synthesis (from each 3′ end in the target molecule) has continued beyond the target site, using each strand of the transposon as template; that is, the transposon has been replicated. The end of each new strand has been ligated to a free strand-end in the donor molecule. The structure shown at (d) is called a cointegrate; the zigzag line represents newly synthesized DNA. Progress from stage (d) to stage (e) involves the activity of an enzyme called a resolvase (which is encoded by the transposon); this enzyme ‘resolves’ the cointegrate by promoting site-specific recombination between sites in the two copies of the transposon – forming the molecules shown at (e). (Continued on page 794.)

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transposon is highly specific: a copy of Tn3 in a replicon confers immunity to insertion of a second copy of Tn3 but not to insertion of a closely related transposon such as Tn501. Apparently, only the terminal 38 bp of Tn3 need be present in a replicon to confer immunity. (cf. MULTICOPY INHIBITION.) transposon (Tn) A TRANSPOSABLE ELEMENT (q.v.) which encodes not only those functions necessary for transposition but also functions that are unrelated to transposition – for example, resistance to antibiotics (see e.g. entries for Tn3, Tn5, Tn9, Tn10, Tn1721 ) or heavy metals (e.g. Tn501 ) or both (e.g. Tn2410 ), toxin production (e.g. ETEC heat-stable toxin: see Tn1681 ), and lactose metabolism (e.g. Tn951 ). (See also conjugative transposons in the entry CONJUGATIVE TRANSPOSITION.) Some transposons (referred to as class I, composite or compound transposons) consist of a sequence containing structural genes flanked on either side by an INSERTION SEQUENCE – the two insertion sequences forming identical or non-identical, direct or inverted repeats; one or both IS elements mediate transposition of the entire transposon (see e.g. Tn10 ) and may also be able to transpose independently of each other and of the rest of the transposon. Other transposons (class II, simple or complex transposons) consist of a sequence containing one or more structural genes flanked on either side by a short inverted repeat (see e.g. Tn3 ). The use of transposons in laboratory studies. Transposons are valuable research tools that have many uses in the research laboratory. Depending on requirements, transposons can be inserted into the genomes of living cells (see e.g. TRANSPOSON MUTAGENESIS and SIGNATURE-TAGGED MUTAGENESIS) or inserted into isolated DNA molecules in an in vitro system. The use of transposons has been facilitated e.g. by the development of a genetically modified form of a natural transposon, Tn5 (see TN5); this system can be used in the following approaches. Transposons can be inserted, at random sites, into a population of plasmids (or other molecules) simply by incubating together the target DNA (i.e. population of plasmids), copies of the transposon and the relevant transposase; incubation is carried out at 37° C for a few hours in the presence of Mg2+ . After incubation, the plasmids (most or all now containing a transposon inserted at a random location) are inserted into bacteria (e.g. Escherichia coli ) by TRANSFORMATION or ELECTROPORATION; most or all of the bacteria will receive a transposon. If the transposon includes an antibiotic-resistance gene, plating the (transformed) bacteria on a medium containing the given antibiotic will select for those cells which contain a transposon. If, after incubating the plate, several colonies are chosen, each colony will contain cloned copies of the plasmid containing the transposon at a given, unique location. How may such clones be used? If the plasmid is a large molecule, then each of a number of clones can be used for sequencing different parts of the molecule – using primers complementary to end-sequences in the transposon for bi-directional sequencing (see DNA SEQUENCING); as plasmids in different clones contain transposons in different (random) locations, sequencing can start from different sites around the molecule. In vitro insertion of transposons, described above, may also be used for modifying a plasmid. Thus, the randomly inserting transposons may, in one or a few plasmids, insert into (and

inactivate) a particular gene, causing a required ‘knock-out’; such a mutant may be subsequently selected for in the population of transformed bacteria. Transposons are also useful for carrying a specific gene into target cells; such a gene is inserted into the transposon. In vivo insertion of transposons may be carried out with the same (Tn5 -based) system: transposons, complexed with transposase in an Mg2+ -free environment, are electroporated into living cells and insert (randomly) into the genome. This procedure may be used e.g. to insert a specific gene (carried by the transposon) and/or to create an insertional mutation in the genome. transposon mutagenesis TRANSPOSON-mediated MUTAGENESIS. Various approaches involving transposon mutagenesis have been used e.g. for detecting/identifying potential virulence genes and/or gene products in pathogenic bacteria. One example is the detection of secreted and/or cell-surface-associated proteins – i.e. proteins which, because of their possible direct interaction with the host organism, are of interest as potential virulence-associated factors. To detect secreted/cell surface proteins, a population of the given pathogen is mutagenized with transposons that contain a promoter-less gene for alkaline phosphatase (phoA); these transposons (TnphoA) insert randomly into the genome in cells of the bacterial population – inserting into different genes in different cells; the cells are then plated so that each cell forms an individual colony. Colonies are tested with a substrate for alkaline phosphatase which, if cleaved by the enzyme, generates colour. This substrate can be cleaved only if alkaline phosphatase has been secreted by the cells or if it is associated with the cell surface; hence, any colony which gives a positive (colour) reaction with the enzyme’s substrate indicates a secreted or cell-surface phosphatase. Because phoA (in the transposons) is promoter-less and lacks a signal sequence (see SIGNAL HYPOTHESIS), production of an extracellular alkaline phosphatase by cells in a given colony indicates that, in these cells, TnphoA has inserted ‘in frame’ into the gene of a secreted or cell-surface protein, and that the signal sequence of the gene has enabled secretion of the phosphatase. The gene containing TnphoA is likely to have been inactivated by insertion of the transposon. If the gene is a virulence gene, the virulence of cells in the colony may be demonstrably reduced when the cells are tested in experimental animals; if so, the relevant (transposon-mutated) gene can be isolated, sequenced and characterized. A system for transposon-mediated mutagenesis in Haemophilus influenzae takes advantage of the specific uptake-signal sequence which facilitates import of DNA by TRANSFORMATION [AEM (1998) 64 4697–4702]. Transposon mutagenesis, using luxAB genes (see BIOLUMINESCENCE) as a reporter system, has been used to identify genes induced in the COLD-SHOCK RESPONSE in Sinorhizobium meliloti [AEM (2000) 66 401–405]. (See also SIGNATURE-TAGGED MUTAGENESIS.) trans-stadial transmission In a tick VECTOR (or, less commonly, an insect vector): the retention of infectious agents (e.g. viruses or bacteria) during the transition from larva to nymph, from nymph to adult, or throughout the entire period of transition from larva to adult. (See e.g. COWDRIA.)

TRANSPOSABLE ELEMENT (continued) (e) Donor and recipient molecules each contain a copy of the transposon; note that, in this model, each molecule contains parts of the original transposon (dashed lines) as well as newly synthesized DNA (zigzag lines). Adapted from Fig. 11.29, p. 336, in Molecular Biology of the Gene 4th edn by Watson et al. Copyright 1965, 1970, 1976, 1987 by James D. Watson. Reprinted by permission of Addison Wesley Longman, Inc.

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Treponema transverse binary fission See BINARY FISSION. transverse microtubules (ciliate protozool.) A ribbon of microtubules which arises at the left-hand anterior side of a kinetosome (near triplets 3–4(−5), GRAIN CONVENTION), extends upwards towards the pellicle, and then passes leftwards at right angles to the kineties, the wider face of the ribbon being parallel to the body surface. (See also RHABDOS.) transversion mutation A type of POINT MUTATION in which a purine nucleotide is replaced by a pyrimidine nucleotide, or vice versa. (cf. TRANSITION MUTATION.) traO locus See FINOP SYSTEM. Trapelia See LECIDEA. traS gene See F PLASMID and SURFACE EXCLUSION. traT gene See F PLASMID and SURFACE EXCLUSION. travellers’ diarrhoea DIARRHOEA in persons outside their normal environment. Enterotoxigenic strains of Escherichia coli (see ETEC) are common causal agents, but almost any FOOD POISONING organism may be responsible. traY gene See CONJUGATION (sense 1b). traZ gene See CONJUGATION (sense 1b). treadmilling See e.g. MICROTUBULES. Trebouxia A genus of unicellular, coccoid, non-motile green algae (division CHLOROPHYTA); species are common photobionts in LICHENS, but they also occur (sparsely) in the free-living state e.g. on wood, bark, etc. The cells are variable in shape and size (up to ca. 35 µm diam.), free-living forms being larger than those in lichen thalli; each cell contains a single large central chloroplast with at least one central pyrenoid. ‘Vegetative cell division’ does not occur (cf. PSEUDOTREBOUXIA). Asexual reproduction involves the formation of biflagellate wall-less zoopores – at least in cells growing in liquid media; in lichen thalli zoospore formation is usually (but not always [Lichenol. (1980) 12 173–187]) suppressed, asexual reproduction occurring by autospore formation. [Trebouxia species from lichens: Lichenol. (1981) 13 65–86.] Trebouxia has been placed – together with e.g. FRIEDMANNIA, MICROTHAMNION, PLEURASTRUM and PSEUDOTREBOUXIA – in an order, Pleurastrales, in the class Pleurastrophyceae (division Chlorophyta) [Book ref. 123, pp. 29–72]. (cf. TETRASELMIS.) tree diseases Decay of standing trees is generally due to fungal attack on the (dead) heartwood, the (living) sapwood being much less frequently attacked. Rotting of the heartwood generally does not affect the vital processes of the tree, but the tree eventually becomes structurally weakened and may be easily toppled in high winds. The fungi which attack heartwood (causing ‘heart rots’) normally gain access to it via wounds – e.g., damaged roots or broken branches. Important tree-rotting fungi include e.g. species of Armillaria, Ganoderma, Heterobasidion, Piptoporus, Polyporus and Trametes. (cf. TIMBER SPOILAGE; see also BROWN OAK; BROWN ROT; BUTT ROT and WHITE ROT.) Other tree diseases include e.g. APPLE CANKER, BEECH BARK DISEASE, BLEEDING CANKER, BLISTER RUST, CHESTNUT BLIGHT, DUTCH ELM DISEASE, FIREBLIGHT, JARRAH DIEBACK, OAK WILT, PITCH CANKER, SOOTY BARK, SNOW BLIGHT, WATERMARK DISEASE and WETWOOD. tree lungwort Lobaria pulmonaria. tree squirrel hepatitis B virus See HEPADNAVIRIDAE. trehalose (a,a-trehalose) A non-reducing disaccharide: a-Dglucopyranosyl-a-D-glucopyranoside. It occurs e.g. in the haemolymph of insects, in certain algae (particularly red algae), in a few plants (commercial source: Selaginella), in actinomycetes and certain other bacteria (see e.g. CORD FACTOR), and as the major storage disaccharide in many fungi

and yeasts and some lichens. Trehalose is hydrolysed by an a-glucosidase, trehalase, present in all trehalose-producing organisms. [Regulation of trehalose mobilization in fungi: MR (1984) 48 42–59.] Tremella See TREMELLALES. Tremellales An order of saprotrophic, lignicolous fungi (subclass PHRAGMOBASIDIOMYCETIDAE) which typically form gymnocarpous fruiting bodies in which the (usually) globose or clavate basidia each consist of a longitudinally septate metabasidium from which arise four elongated sterigmata. According to species, the basidiocarp may be e.g. crust-like, sheet-like and convoluted, or erect and stalked, it may be gelatinous (see JELLY FUNGI), waxy or leathery, and it may be e.g. orange, pink, brown or black. Genera include e.g. Aporpium, Exidia (E. glandulosa = ‘witches’ butter’), Phlogiotis, Pseudohydnum, Tremella. (See also TETRAGONIOMYCES.) tremorgenic Capable of inducing tremors. (See e.g. PENITREMS.) trench fever (Wolhynian fever) A louse-borne disease of man caused by Bartonella quintana (formerly called Rochalimaea quintana). The incubation period may be a few days or longer than a month. Symptoms include fever, severe muscular pain (particularly in the back and legs) and sometimes a maculopapular rash that occurs on the chest and abdomen; splenomegaly is common. Mortality rates are low, but complications (e.g. cardiac dysfunction) may occur, and relapses may occur in untreated patients. XENODIAGNOSIS has been used in the past, but diagnosis can now be achieved by culture and/or by complement-fixation tests and other serological approaches. The disease usually responds to chemotherapy with e.g. tetracyclines or chloramphenicol. trench mouth Syn. VINCENT’S ANGINA. Trentepohlia A genus of non-aquatic filamentous algae (division CHLOROPHYTA) which shares many features with e.g. CEPHALEUROS, PHYCOPELTIS and STOMATOCHROON [Book ref. 123, pp. 233–250]: the thallus is commonly heterotrichous (except in Phycopeltis), i.e., it is composed of more or less well-developed erect and prostrate systems of filaments; an orange-red pigment (‘haematochrome’) is stored in the cytoplasm; pyrenoids are absent; and zoospores and gametes are produced in specialized cells from which they are released via a single papillate exit pore. The flagella of the motile cells are characteristically bilaterally ‘keeled’ or ‘winged’. In Trentepohlia spp, the erect system of orange-red filaments is well-developed, the prostrate system weakly developed. Species grow on rocks, wood or bark, or as photobionts in certain lichens (see e.g. OPEGRAPHA and ROCCELLA). (See also ERYTHRITOL; PAINT SPOILAGE; RIBITOL.) Trepomonas See DIPLOMONADIDA. Treponema A genus of Gram-negative bacteria (family SPIROCHAETACEAE) which occur as parasites or pathogens in the mouth, intestinal tract, and genital regions in man and other animals; some species are obligate anaerobes, but others (including T. carateum and T. pallidum) are now generally considered to be microaerophiles. The cells are helical, 0.1–0.4 × 5–20 µm, and motile; they stain poorly by the Gram stain but satisfactorily with silver deposition methods (see e.g. FONTANA’S STAIN). T. pallidum, T. carateum and T. paraluiscuniculi have not been grown in cell-free media, and are propagated e.g. intratesticularly in rabbits (see also NICHOLS’ TREPONEME). The other (obligately anaerobic) species have been grown in complex media and have a fermentative metabolism; isolation procedures are based e.g. on insensitivity to rifampicin, or on the ability of the cells to migrate through a membrane filter (pore size 0.2 µm) into, and through, a suitable agar medium. GC%: 25–54. Type species: T. pallidum. [Book ref. 22, pp. 49–57.] 795

Treponema pallidum immobilization test T. bryantii. Occurs in the bovine RUMEN; cells ca. 0.3 µm in diameter. Cultivable in media containing e.g. isobutyrate, pyridoxal, folic acid, biotin, thiamine and niacinamide. GC%: ca. 36. T. carateum. The causal agent of PINTA. The cells are similar to those of T. pallidum (q.v.). T. denticola. Occurs in the mouth (particularly the tooth – gum margin) in man and primates; cell diameter