QUARTERLYMAGAZINE OFTHE SOCIETY FORGENERAL MICROBIOLOGY VOLUME2g AUGUST 2OO2

Eukaryoticmicrobes: something for everyone

Fungalpathogens -the devilis in the detail DNAdamage responses

Goinggreen:the evolution of photosyntheticeukaryotes

Newhope forthe neglected diseases

What'sfor dinner - howdo f ungichoose whatto eat? Survivalby cAM P insocial amoebae

Badgersand bovine TB SGMHeadqualtets MarlboroughHouse, Articles BasingstokeRoad, Spencers E_ukaryotic Wood,Reading RG7 1AG microbes: somethi ng for everyone Tel.01 I BgBB1800 ClivePrice 119 Fax01 189885656 -the emailmtoday@sgm,ac.uk Fungalpathogens devilis in the detail AlistairJ.P. Brown SGMWebsite 120 http://wwwsgm.ac.uk DNA damage responses :a combi nation of maintenance Editor andfire-fighting Fiona E. Benson &Antony M. Carr 123 DrMerielJones Goinggreen:the EditorialBoald evolutionof photosynthetic ProfessorDave Kelly eukaryotesSaulPurton 126 DrLynne Macaskie NewhopefortheneglecteddiseasesPaul McKean 129 ManagingEditor JanetHurst What'sfor dinner,what shall I choose?Mark X. Caddick 132 PrcductionEditor Survivalby cAM P insocial amoebae:an intersection lanAtherton betweeneukaryote and prokaryote signalling systems AssistantEditorand PaulineSchaap BookReviewManager 130 JaniceMeekings Equalopportunities inmicrobiology research careers? Gontributions LizSockett j4O Theseare always welcome and shouldbe addressed tothe Editor (c/o SGM Headquarters). CopyDates Regular Features Lastdates for receipt of copy atMarlborough House are: SocietyNews GeneralCopy MayCouncil Meeting 142 November2OO2issue 2 Seot, AnnualGeneralMeeting 142 Februarv2003issue 2 December Above: Trypanosoma FionaBenson and Tonv Carr StaffNews (CRC) 142 Adveftiiements brucer,the sleepin g sickness (pp,123-125)describe Grants 142 November2002issue 30 Sept. parasite, past February2003 issue6 January moving human howtheintegrity of genes PrizeLecturers 143 redblood cells.John Bavosi/ ismaintained, Advertisements SciencePhoto Library. Meetings 144 Allenquiries should be sentto: Thechloroplast isthe site Helen GoingPublic Sapsford,NWH Sales Ltd, Vol.29,Part3, of photosynthesisin plant TheArcadeChambers, BUGs- bad,ugly and goodJoy Perkins 146 TheArcade, Aldershot. August2OO2 andalgalcells, Saul Purton (pp, Hampshire,GUlllEE Inthis issue we celebrate explains 126- 128)how SchoolZone 147 Te|,01 252 357000 thisimportant organelle theformationof a newSGM Gradline Fax0 1252 357001 evolvedfrom a photosynthetic 148 [email protected] specialinterest group which bacterium. HotoffthePress aimsto supporlthe study of Remarkably, Subscriptions2(J()2 parasitic NON-MEMBERS eukaryotic certain protistsalso microbiology.lt plastids Reviews i b8 Mic ro bio I ogyTodayS50.0O willprovide aforum forthe have whichindicate (us$85.00) photosynthetic AddressBook jG2 discussionof the molecular; ancestors, MEMBERS cellular Thesemay be a possible SGMStaff All membersreceive Microbioloav andorganismal 16b biologyofeukaryotic targetforthe drugs which Today.lnadditionthey m aylake"' aredesperately needed in Comment anyofthe Society's journals. microbessuch as filamentous thefight against protozoan Confusionover bovine tuberculosis in badgers, OrdinarvMember fungi,yeasts, slime moulds, cattleand humans? MembershioSubscriotion protozoaand microalgae, diseases,as PaulMcKean 1G6 (in (pp, c.M i c ro 6 i o t o g y Told ay) asnew convener describes 129-1 31). Diary s42.00(us$72.00) ClivePrice 168 Microbiology/JGV/ lJSEM describeson p. 1 19. Thesocialamoeba isa (us$ s75.00 140.00) Comparedwith bacterial fascinatingorganism which Studentor Reti redMember pathogens,only afew fungi usesthe cAM.P sig nalling Other ltems MembershipSubscription systemio controlthe (inc.M i cro b i o I o gy Tod ay) causelife-threateni ng Letters 118 c20.00(us$35.00) infectionsin humans, As disseminationof its sporesr as Pauline Microbiology/ JGV Al Brownexplains, these Schaapexplains ProposedUK LifeSciences Federation Ron Fraser 184 s3700(us$70.00) onpp, 1 36-1 38. tJsEM s7 5.OO (US$ 1 40.00) mycosesare becoming more BookReview: prevalent,are harderto treat Und erg rad uate or School M em ber Equalopportunities are Encycl o ped i a of Envi ro n m e ntal Mi cro bi ol ogy 138 (inc. andare often diagnosed too impodantforpeople who MembershipSubscription SGM primary school competition M i crob i ology Today) I 10.00 late(pp, 120-122). One of takeacareer break, orwho 139 Corporate Member the reasonsfungi can exploit haved isabi lities. Ed ucation LifeScience Careers 2002 149 MembershipSubscription (inc. so manyniches is they can OfficerLiz Sockettlists some InternationalDevelopment Fu nd report M ic rob io I o gy Today)$500.00 metabolizeawide range of ofthe schemes now available lmprovingwaterqualityinChinaGwynJones The views expressedby compounds,Mark Caddick anddescribes new legislation 1D4 contributorsare not necessarilv exploreshow, given achoice, thatwillaffect all universities InternationalResearch Fellowship report those of the Society;nor can the (pp, claimsof advertisersbe theyselect what they eat 1a0-1 a1), Typin g Can d i d a p ar a pslosrb strai ns f rom neo n ates (pp.132-13a), RomaBatra guaranteed. Thesearticles appear in lbo O 2002 The Societvfor General TheDNAin everyliving additionto alltheregular BookReview: Microbiology;I SSNi 1464-0570 cellis constantly subjected featuresand reoorts of Encyc I o ped i a of Life Scie n ces 157 Desig n : G rap h i cs Inte rn ati on al to damagingevents. Sociefuactivities, f,l

Lettersto theEditor Bioremediation inspiration Reaction to anthrax rGomment, article - arewelcome and Dear Editor Professor Titbalt replies shouldbe emailed to 'putting The articleson microbesto work' in the May Dear Editor [email protected] MicrobiologyToday and particular in thosethat Dr Hambletonhas kindlycopied his letterof 1 March, focussedon bioremediationwere nice orsent to SGM HO, to see and gave concerninganthrax vaccine, to me (see Mav issueof somegood introductions parts SGM reservesthe to of the bioremediationMicrobiologyToday,p.62).1am pleasedthat Dr Hambleton world, However,they also gave righttoedit letters a somewhat roseate foundthis article enjoyable, With respectto hisspecific impressionof the importanceand potential need for micro- points: priortopublication. biologyand bioremediationin dealing with our historic oollution, 1, The data sheet providedwith older batchesof the 'When anthraxvaccine reads: Anthrax vaccine(Atum lf bioremediationis to grow in importanceit is vitalthat precipitatedAnthrax Antigens) is for the active immuniza- we understandthe extentof the problems that arefaced. tion of man against the various forms of anthrax, four Expressionsof the amountof land wherecontaminants are doses of O5 ml should be given intramuscularly.The three presentare alwaysimpressive, But much of this land dosesshould be given at intervalsof 3 weeks,followed bv may not need to be treated, Certainly,in the UK the a foufth dose at an interuatof Omonths. Reinforcing dosis legislationonly requires actionon landiontamination if it of 0'5 ml intramuscularlyshould be given annuallll, can be demonstratedthat the contaminantsmay, or do, The causesignificant harm or if theypollute a controlledwater. datasheet provided with the latestbatch of anthrax vaccine 'The Siteswhere this can be saidof a metalmav be few and that we havereceived at Dsil reads: primary (first) far between;rather it is normallyorganic contiminants that course of four single injectionsis followed by'a drivethe risksassociated with land contamination. bogsterdoge-given once a year. For each doseyour doctor willinject O5 ml of the vaccineinto a muscle.'ihe accom- Bewarealso of underestimatingchemical or engineeringpanyingtable shows: solutionson contaminatedsites since manv of the problems(and thus the costs)of implemeniingihese will Injection Whenwill the injectionbe giuen? (micro)biological alsoapply to active methods, Firstinjection (05 ml) Firstvisit JonathanLloyd is rightthat for bioremediationto prosper o ^-'|- -i- r' r Secondiniection (0,5m|) . J WeeKSaTler ilrst Injection ",-- there must be a true multidisciplinaryapproach. li is importantthen that microbiologistsunderstand not only Thirdinjection (0,5ml) 3weeks aftersecond injection theirown discipline,but alsothe regulatorycontext and Fourthinjection (0,5ml) 6monthsafterthird injection the otherdisciplines involved. The establishmentof the FIRSTFaraday Partnership for remediationplus the DTI Booster unceayear LINK Programmeon Bioremediation bothgive excellent The data sheet associatedwith the older batchesof vehiclesfor bioremediation to developin the UK.The latter vaccinedoes state that the vaccineis producedat CAMR needsgood proposals from microbiologistsand others. PortonDown, butthis informationis not providedwith the Lastly,the remediationof allcontamination is unaffordable,newdata sheets, Microbiology musttherefore play a keyrole in understand- 2, The UK anthraxvaccine is statedto contain'significant ingthe environmental cApacityfor naturalattenuation of but varyingamounts of contaminatingtethal faLtor and contaminants,This should providea hugedriver for the oedema factol (1). lf the amounts vary and are not betterunderstanding of fundamentalmicrobial ecology of controlled,then one cannotbe certainthat somebatches soiland the subsurfaceso that regulatorscan understand (orsome past batches) will not contain these antigens, 'mal The whenintervention is neededand when not text reads becausethe additionaltoxin 'may' components O DrAlvvyn Haft, Programme and Information impartside effects, M a n ager, Nationa I rou G n dwater a n d Conta m i nated 3. Nowherein this articledo I statethat pA is the only Land Centre, Environment Agency, protectiveantigen, merely that it is the activecomponeni Tel.0121711 5879;Fax0t2t 71t 5925 of the vaccine.We are activelysearching for additional vaccineantigens at DstlPorton Down. Of the articlescited whichidentifies additional antigens, Boiling two werepublished muds and scalding soils afterthis commentary was written, and neither of these - ProfessorJohn Postgatehas pointed out an inaccuracv articlesidentify any additional antigens theydo suggest 11my a.rticleprblished in the last issueof Microbiology thatadditionalvaccine antigens exist, The third (price?a/. Today(May 2002, p,64). The blacksmoker ecosysrems 2001) refersto protectionagainst anthrax toxin, not protection are not completelyindependent of solarenergy input; against anthrax. althoughthere is no sunlightin the abyssal depthi, down- O Professor Richard W Titbail, Dsil, porton Down, wellingoxygen, usedin the sulphuroxidation reactions, is Sal isbury Wiltsh ire, It K. photosyntheticallygenerated in surfacewaters. So isthere anyecosystem that is truly independent of solarenergy? 1. Brachman, P.S. & Friedlander,A.M. (1999).Anthrax. In Vaccines,3rd edn.Philadelphia:'W.B. Saunders. O Professor David Lloyd, Microbiotogy, Cardiff University, PO Box gt5, Gardiff CFIO gTL, atK Tel. 029 20874772;Fax 029 20e7/rg}s e m a i I I I oyd d @card iff.a c. u k

N/AUGW

the detail AlistairJ.PBrown

Compared Fungi are eukaryotes,and are more closely withbacterial relatedto humansthan bacteria.Some protein pathogens,a components of fungal and human cells For example, relativelysmall are even functionally interchangeable. human proteins with fundamental roles in the cell numberof fungal division cycle, stressfesponses, gene regulation, protein speciescause Iocalization, metabolism and in energy generation, can life-threatening functionally replace the corresponding proteins in the infectionsin budding yeast, Saccharomycescereuisiae. An important humans.However, consequenceof this is that it is harder to identify the thesefungal significant differences between fungal and human cells infectionsare that might make useful targets for antifungal therapies. becomingmore Relatively few antibiotics are available to fight fungal prevalent,theyare infections. These include azoles, polyenes, flucytosine hardertotreat, and echinocandins, which block ergosterol biosynthesis, permeability, block andthey are often interfere with fungal membrane nucleic acid biosynthesis and inhibit cell wall B-glucans, diagnosedtoo respectively. The celi wall is different in fungal and late, human cells, and hence fungal cell wall biogenesis is a major target for the development of new antifungal drugs.

S Fungalopportunists Microbial pathogens can be divided into those that cause disease in healthy individuals (primary pathogens), and those that only tend to do so in enfeebled hosts (opportunistic pathogens). Many of the maiot bacterial pathogens are primary pathogens. For example, Bacillus ant hraci s, E scheri ch i a coI i, Lis taia mnnlcyt0 genes, S a lmoneI I a typbimurium, Shigella flexneri and Yersinia pestis invade and colonize healthy individuals. In contrast, relatively few fungal species arc primary pathogens. They include Histoplasna capsulaturn, Corcidioidu inmitis, Para- coccidioidesbrasiliensis, B lvstomycesderntatitidis and the dermatophytes (i.e. those fungi that infect the skin). Other major fungal pathogens such as Candida species (r.g. C. albicans, C. glabrata, C' tropicalis, C. dubliniensis), Coccidioidesimrnitis grows in dry alkaline soils. The brasiliensis is not Asp erg i I I us furui gat us, P eni ci I I i um marn efei, P neumo cy s t i s environmental source of Paracoccidioid'es carinii, Rhizopus nryzae and Fusarium solani are clear, but it is known that most people in endemic TOPRIGHT: opportunistic pathogens. These fungi only tend to regions are exposed to the fungus before they rcach 2O Slg.t . Conidiaproducing the cause life-threatening systemic infections in patients years old. H istop lasna capsulatum, C occidioidesimntit is and infectivespores ofAspergillus with severely compromised immune systems. Crypto- probably Paracoccidioid.esbrasiliensLr infects people by the funigatus. cnccus neoformans can cause community-acquired inhalation ofdust containing high concentrations of this PHOTOEGUEHO, CNRI/ SCIENCEPHOTO LIBRARY infections, but mostly infects immunocompromised fungus. They colonize the lung, initially causing patients. Hence, this fungus appears to lie somewhere pulmonary infections, but then they can spread to other BOTTOMRISHT: between the extremes of opportunism and primary internal organs. Aspergillus furnigatils is also widespread S$6.R. White patches of pathogenicity. in the environment (Fig. 1). Again, its primary route of growingona Candidaalbicans Histoplasnta capsulatum infections are widespread infection is via inhalation into the lung where it can patrent'soesophagus. regions around the world, grow rapidly to form large boluses of fungal cells in the PHOTODAVID MMARTIN MD/ in tropical and temperate SCIENCEPHOIOLIBRARY whereas P aracoccidioidesbras i I iensls infections are limited immunocompromised patient. P neumocy s t i s carin i i also to Latin America. In the Americas, Coccidioidesimnitis infects via inhalation of spores,germination and invasion OPPOSIiEPAGE: infections are mostly restricted to hot, dusty climes. of lung tissue. This unusual fungus was originally $$9.$" Cryptococcusneofornans These geographical distributions appear to be related to classified as a protozoan parasite, until recently when protective formsathick pathogens DNA sequencing revealed an evolutionary relationship polysaccharidecoalin vivo. the environmental niches that these fungal yeasts. All of these fungal infections PHOTOALFRED PASIEKA/ occupy outwith their human hosts. Histoplasrna to ascomycetous SCIENCEPHOTOLIBRARY capsulatum grows in bat or bird droppings, whereas canprove fatal.

lE N$$SNSW$S$kSWTODAYVOLn / AUGO2 Candida albicansis the most common causeof systemic integrin-like protein and an Hwpl protein that acts as a fungal disease.This fungus is found in warm-blooded target for host transglutaminases that actually cross-link mammals, but a clear niche for Candida albicans has not fungal cells to host cells. Candida albicans also secreres been identified in the environmenr outside of irs hydrolytic enzymes that presumably damage host tissue mammalian host. This fungus exists as a commensal in and possibly provide nurrienrs for the fungus and most (healthy) individuals (Fig. 2), but when the promote fungal invasion. Large gene families of secreted delicate balance between the fungus and its host is aspartyl proteinases (SAPs) and lipases (LIPs) are 'superficial' disturbed, Candida a/bicans can cause regulated differentially during diseaseprogression in infections of the mouth and vagina (thrush). Most different host niches. This fungus has also learnt to adapt women suffer at least one episode of vaginal thrush to the neutral pH of the bloodstream and more acidic pH in their lifetimes, but these infections can become of the vagina. Canclida albicans virulence is attenuated recurrent in some unfortunate individuals. Oral if these pH responses are disrupted. Like Cryptlcnccus infections are common in new-born infants and in AIDS neoformans,Candida albicans exploits various srraregies patients. In patients with a severely compromised to evade host defences. For example, Candida albicans immune system, Candida a/bicans can enter the blood- releasescarbohydrates from its cell wall that modulate stream, become disseminated throughout the body host immune responses, and it also undergoes rapid and invade internal organs. Transplant patients on switching between different phenotypic forms. immunosuppressive drugs and cancer patients under- Virulence is affected ifeither ofthese events are blocked. going chemotherapy are most at risk. Many of these Cellular morphogenesis also plays an important role systemic Candida albicans infecrions are fatal. These in fungal virulence. Aspergillus furnigatus is a filamentous fungal infections are becoming more prevalent world- mould, which generares infective spores. Cocciclioides wide because the size of the immunocompromised immitis also grows in a filamenrous form in the patient population is rising. environment, but it switches to a specialized growth form upon contacr with the host. This fungus forms qSVirulence factors large spherules in the lung, each of which releases Bacterial pathogens appear to rely upon a small number hundreds of endospores into the host. Similarly, the of key factors for their virulence. Purified cholera and environmental and parasitic forms of Histoplasma tetanus toxins can themselves confer most of the effects capsulatum, Coccidioides immitis and Paracoccidioides of Vibrio cholerae and Clostridium tetani, respectively. brasiliensisgrow with different morphologies. These Also, the inactivation of toxin genes can attenuate fungi form mycelia in the environment, but grow in a bacterial virulence. In conrrast, knocking out gliotoxin yeast-like form inside their host. Paracoccidioides production does not render Aspergillus fatnigatus brasiliensis is particularly interesting, because the avirulent. Hence, fingal pathogens appeat to display transition to the yeast form is inhibited by oestradiol. more complex virulence traits. Many factors appear, This probably explains why women are about 50 times to promote fungal virulence, and the expression of lesslikely to sufferparacoccidioidomycosis than men. any single factor does not confer pathogenicity upon a Clearly, morphological transitions are important benign fungus. for the pathogenicity of these fungi. However, rhe Several factors contribute to Cryptococcusneoformans situation is less straightforward in Candida albicans. virulence. A thick polysaccharide capsule protects This fungus exists in yeast-like, pseudohyphal and this fungus from host immune defences (Fig. 3). The hyphal forms in aiuo. k coat inhibits phagocytosis and modulates immune is often assumed that responses.Melanin production protecrs Cryptococcus the hyphal growth form neoformansfrom attack by reactive oxygen species, enhancestissue invasion, thereby reducing the potency of leukocyte killing. whereas the yeast form Virulence might also be promoted by the secretion of promotes dissemination of mannitol into the cerebral spinal fluid. Also, mating fungal cells in the blood- type is clearly linked to Cryptococcusneoformans virulence, stream or between indi- becauseclinical isolates mostly have the MATagenotype. viduals. Although this The explanation for this seems to be that mating and assumption might pfove ro virulence factors are both regulated by the same signal be correct, it remains to be transduction pathway. confirmed experi mentally. Candida albicans also displays a battery of different The problem is that yeasr- virulence factors. This fungus expressesalargenumber of hypha morphogenesis is adhesinsthat help the fungus stick to host cells and gaina intimately linked with foothold in the eady stages of infection. These adhesins the expression of other include afamlly of agglutinin-like sequences(ALSs), an virulence factors, including Table L Examples of common virulence stmtegies in fungal and bacterial pathogens

Uirulencefactors Bacterialpathogens Fungalpathogens ffiToxins [holera,diphtheria, perlussis, tetanus, haemolysin AEergillusfumlgaFusgliotoxin,ribotoxins ffi Adhesion Fimbrialadhesins o{Haenophilus,Helicobacter, Escheilchia |;andidaagglulinin-like sequences species Afimbrialadhesins ofBordetella,Salmonella, Staphylococtus Candida albicanstransglutaminase targets(Hwp1) SOECIES ffi Invasion Myco plnn a, Y usi ni a, Sal na n el Ia, Jrlrgela speci es fl,istoplasmainuasion Candidaalbicanssecreted aspartylproteinases (SAPs) and lipases(LlPs) Morphogenesis inCandi da albicans, Paracoccidioides, Caccidio i d e s, H isto pI as m a ffiEvasion Streptococcal /Verssena capsules Cryptococcalcapsules lmmunomodulationbyMycoplasma, Estheri chia speties lmmunomodulationbyCandida albicans Pse udo m o n as, Streptococ cus c0 nt pleme rrtinactitlati 0n Candida albicansphenotypic switching Salnonella, Neisseria antigenic variation

Further reading adhesins and proteases. These virulence factors must be vaiety in the specific mechanisms by which microbes dissected individually before we can assesstheir true interact with their human host. However, despite the Borges-Walmsley,M.I., contributions to the pathogenic ity of Candida albicans. apparent complexity of fungal virulence attributes, Chen,D.,Shu,X.& \X/hat is clear is that the pathogenicity of this fungus many fungi and bacteria appear to adopt similar Walmsley,A.R. (2002). (Table 1). Both fungal and bacterial Theparhobiologyof is complex: it is not dependent upon any single infection strategies po ro,'s,'1' i / ) n) Jt s l,ra s i / i en.r i s. virulence trait. pathogens must be capable of adhesion, invasion and TrendsMicrahiol 10,80-81 . colonization. They must both be able to grow well at iiii of vi rulence 37 "C and they must evade the immunological defences Calderone,R.A.& Evolution proteases ofthe host. However, the devil is in the detail. Fonzi,W.A.(2001). Bacterial pathogens produce adhesins and Virulencefac tors of Candida as well as toxins. The genetic analysisof these traits has a/ bicans. Tren ds M it'robi ol 9, led to the major revelation that many arc organized O Alistair J. P. Brown rs Prolessor in Molecular 'pathogenicity 327-33t. within islands'. These genes are located and Cell Biology,Aberdeen FungalGroup, alongside genes lnstituteof MedicalScrences,University of Finlay, B.B. & Falkow, S. together in the bacterial chromosome, appantuses that Aberdeen,Aberdeen AB25 2ZD, UK. 0997).Commonthemes encoding the specialized secretoty in nricrobialpathogenicity target these virulence factors to the host. These patho- Tel.01224 555883; FaxOl224 555844 revisited.Min'obiol Mol Biol genicity islands may provide a means for the horizontal emai I al.b row n @abdn. ac. u k Rea6l,136-169. transfer ofvirulence genes amongst bacterial strains. Haynes,K. (2001).Virulence This is not the casein fingal pathogens. In general, in Can di da specres.'frencls fungal virulence genes are unlinked, and the regulatory Microbiol9 ,19I-J96 . mechanisms that control fungal pathogenicity must for the distribution of virulence genes around Kozel,T.R.(I995). account For Virulencefactors of the genome. There are some exceptions to this. Cry pt ococcus n eoforrnan s. Trenr/s example, tandem copies of SAP and ALS genes exist in Microhol3,295-299 . Candida albicans. Also, tandem copies of putative adhesin genes have arisen near the ends of Candida Odds,F.C.,Gow,N.A.R. virulence & Brown, A.J.P.(2001). glabrata chromosomes. The location of some Fungalvirulence studies genes close to telomeres might be no coincidence. comeofage. Genome Biol 2, Telomeric regions appear to evolve rapidly, allowing 1009.1-1009.4. the rapid amplification (or loss) of niche-specific genetic event might have VanBurik,J.-A..H. & functions. These types of Magee,P.T. (2001). Aspects been particularly important in the evolution of fungal of fungalpathogenesis in pathogens. humans.A nnu ReuM i crob i o/ >), l+)-t / z. ,:r',Invasion strategies Routes of infection and sites of colonization vary for different microbial pathogens. Hence, there is enormous

il IE r;frr.,::,i,i.rr.i:,f r,::i, .:,rai:i'':i' TODAYVOL29/AUG 02 DNAdamageresponses: a combination of maintenanceand fire-fighting FionaE. Benson &Antony M. Carr

All cells rely on DNA to transmit genetic put these right by copying from the undamaged strand. TheDNA in information and it is vital ro maintain Probably these routine maintenance operarions occur everyliving cell the integrity of this information. This is unseen, i.e. they are not monitored by the cell as a sign underlined isconstantly by the tact that in both prokaryores and that somerhing is wrong. However, induced DNA eukaryotes subiectedto around J 7o of the genes are devoted to damage, such as distortions in the double helix which encoding DNA repair and DNA damage response may result from exposufe to the ultraviolet component damagingevents, proteins. of sunlight, or DNA srrand breaks induced by ionizing FionaBenson and DNA itself is fragile and undergoes a host of radiation, require more complex repair pathways such TonyCarr describe interactions with endogenous molecules in the cell. as nucleoride excision repair (NER), homologous hg* the integrity It has been estimated that every cell in our body suffers recombination repair (HR) and non-homologous end oTgenes ts 10,000 DNA damaging evenrs every day. Add to this joining (NHEJ). These pathways can perhaps be maintained, the intrinsic infidelity of DNA replication and the considered as the emergency services, being recruited exogenous damage induced by exposure to sunlight to sort out problems that hopefully do not occur too and other genotoxic treatmenrs (smoking, X-rays, etc.) often and which, when they do occur, can have fatal and it is clear that DNA damage responsesare key to consequences.Certainly it seems that these pathways the survival of an unaltered genome. Preservation of are not silent, but are monitored in the cell by a series a stable genome is critical; genome alterations have a of mechanisms which are collectively called DNA- fundamental role in initiation of cancer in higher integrity checkpoints. eukaryotes. The genome has often been likened to an r$DNA-integrity checkpoi nt pathways encyclopaedia \When of technical information for building a the cell detects DNA damage or its repair (we still complicated machine. The entries in the encyclopaedia do not know precisely how this occurs), it responds in are composed just of a four-letter base alphabet, different ways, depending on the circumsrances it finds comprising A for adenine, G for guanine, T for thymine itself in. For simple eukaryotes, such as yeasr,every cell and C for cytosine. It is the precise ordering ofthese four is going to reproduce, so the differenr responses are letters of the alphabet in each individual encyclopaedia largely geared to keeping the encyclopaediaintacr, rhus entry, or gene, that provides the instructions for making ensuring that the blueprint remains unchanged. To do the proteins that are the key cellular building blocks. In this it is necessaryro arresr the cell cycle and co-ordinate a simple eukaryote such as yeast there are approximately DNA repair with whatever is on-going at the time. For l2million basesencoding 6000 genes. That's 6000 example, if the cell is undergoing DNA replication, individual entries in a hypothetical encyclopaedia just to equivalent to making a copy of our entire hypothetical make a yeast! encyclopaedia, then the repair appararus must inreracr In humans there are about 3000 million letters of with the replication apparatus and stop the latter DNA and about 30,00040,000 genes. Now, ifthere a4p temporarily, since copying damaged information is 10,000 spontaneous DNA damage evenrs in each cell, likely to exacerbate the problem. If however the DNA then it's like somebody randomly erasing 10,000lerters replication is complete, then it is importanr nor to rry in the encyclopaedia every day. Even though less than and separate the replicated copies (i.e. undergo mitosis) 2% of the human genome actually encodesproreins, a until repair is complete. This is important for two latge number of these erasureswill still affect anentry in reasons. First, if the DNA is physically broken our hypothetical encyclopaedia. (analagous to rearing apage out ofour encyclopaedia) Fortunately, the double-stranded narure of DNA then pulling the two DNA molecules apart is going to allows single baseerasures to be fixed with high fidelity- result in the information (i.e. the page) being left behind. information lost from one srrand can be replaced by Second,if the DNA is broken, and still side by side with referring to the alphabet order on the other strand. Some an intact copy, it is possible ro use the information from fotms of damage are more severe and delete lerrers the intact volume to effect repairs to the broken one. This opposite each other. This is a much more severeproblem pfocess, homologous recombination, requires that for a cell. the two identical volumes of the encyclopaedia are in close proximity until the repair is completed. Recent WDNA repair pathways data suggesrs that co-ordination of homologous How does a cell deal with all these problems? First, recombination is controlled by the checkpoint proteins. intrinsic damage to single letters is repaired by a variety In multicellular organisms, many cells are terminally ofmechanisms designed to housekeep the encyclopaedia. differentiated and are nor going to divide again.It is not These DNA repair pathways, which include base clear exactly what the DNA damage responsesare in such excisionrepair and mismatch repair, can essenrially be cells, since most work in laboratories is performed thought of as maintenance workers which recognize on dividing cultures. Clearly, stationary phase - or inappropriate changes in the double-stranded DNA and quiescent - cells can repair DNA damage and their

ili.r.':i:i-r,ri:"IODAY VOL29IAUGA W I 1 i

RIGHT: checkpoint pathways A Sch izo s acch aronyce s p o nb e still operate. Obviously, checkpoint-defectivecellfollowing arresting the cell cycle is abortivemitosis Top: DNA false- in a stationary- colouredingreen, microtubules in not an issue redand spindle pole bodies inblue phasecell, and in this case Bottom:thesame image checkpoint pathways superimposedontoan optical seem to act mainly to imageofthe cell (DNA blue induce other responses, microtubulesred,spindle poles green). for example, initiating WITHTHANKS iOIAIN HAOAN transcription to ensufe an adequate repair fesponse and to make sure repair pathways are properly controlled. bypass are induced aspart of the SOS response, in parallel Another function of the checkpoint pathways is to help with temporary cessationofcell division. Once the DNA co-ordinate a cell suicide fesponse,termed apoptosis. is repaired, the emergency repair systems are turned off This response is thought to remove cells which have and cell division is allowed to proceed. Remarkably, the received particularly dangerous levels of DNA damage. mechanisms of DNA repair processesare essentially It ensures that damage does not become fixed as a conserved from prokaryotes, through simple eukaryotes mutation, or permanently changes an encyclopaedia to complex multicellular organisms, such as man. In entry, which might result in a cell beginning to cycle many cases,pivotal repair enzymes show a high ievel of again and potentially initiating tumour formation by conservation ofsequence and structure from bacteria, inappropriate division. through simple eukaryotes, such asyeast, to man. In view In contrast to quiescent cells, stem cells are of the increased complexity of eukaryotic organisms it is programmed to divide, primarily to give rise to perhaps not surprising, however, that the complexity differentiated cells ofspecific cell types, but also to self- of the enzymatic machinery that mediates repair is renew, as paft of the growth and maintenance of the increased approximately 10-fold between bacteria whole organism. In these cells, it is particularly and man. important to repair DNA damage and to monitor this so that the cell can respond appropriately. A dividing ,ri:From microbesto man cell must be kept under strict control in a multicellular Study of prokaryotes has been important in elucidating organism, since it is one step closer to forming a tumouf rcpafu pathways and providing a paradigm in the SOS than a quiescent cell simply by virtue of being responsefor study of eukaryotic DNA damage responses. programmed to divide. Perhaps unsurprisingly, stem However, studies of single-cell eukaryotes have proved cells appear to have a lower threshold of DNA damage to be of increased importance in delineating DNA repair for the cell suicide responsethan quiescent cells. The and checkpoint responsesof relevance to multicellular logic of this may be that, as dividing cells are more eukaryotes such as man. Clearly, such cells do not have dangerous, it is better to sacrifice the individual cell a suicide response(it's better to try and divide, sincethere when there is a chance of corrupting the blueprint, rather is nothing to lose). However, it is clear that the same than potentially risking the integrity of the whole fundamental eukaryotic surveillance pathways organism. The critical role of DNA repair and DNA characterized in yeasts and other model eukaryotes damage response pathways is emphasized by the report both to cell cycle regulators and the apoptosis observation of the devastating consequencesof inherited system in multicellular systems. genetic defects in these pathways in diseasessuch as Xeroderma pigmentosum and Ataxia telangiectasia. O Dr FionaE. Bensoncan be contactedat Departmentof Biological Sciences,Institute of ,iii:Simila rities between prokaryotic a nd Environmentaland NaturalSciences, Lancaster eukaryotic microbes University,Lancaster LAl 4YQ, UK. Prokaryotic organisms face a similar challenge to simple Tel.01 524 593837;Fax 01 524 843854 eukaryotes in the event of damageto their DNA. As each em ai I f. b en so n @lan caster. ac. u k prokaryotic cell is destined to divide, the focus of the O Professor Antony M. Carr can be contactedat DNA repair and damage response is in protecting the GenomeDamage and StabilityCentre, University integrity of the genome. Suicide is not an option! In of Sussex,Falmer, Brighton BNI ?RR,UK. bacteria DNA damage and repair are continually Tel.01 273 678122; Fax01 273 678121 monitored and a primitive damage response, termed the [email protected] c.uk or SOS response, is activated to co-ordinate repaft and cell [email protected]. uk division. Emergency repair pathways of nucleotide excision repair, homologous recombination and lesion

IE is.$gi;iiii$l;Fi!r$:*tl"iilr,tij!:i ;;r'5"1Q[IAYVOLD/ AUGO2 Goinggrcen : the evolution of photosyntheti c eukaryotes SaulPurton

Thechloroplast Look around our macroscopicworld and evolutionary time. Ultimately, the once autonomous you see a rich diversity of photosynthetic cyanobacterium became an integral and essential isthe site of - photosynthesis eukaryotes.A fantasticrange ofplants covers component of the eukaryotic cell the chloroplast (see (seaweeds) This first truly photosynthetic eukaryote inplant and algal our land and numerous different macroalgae Figs 1 and2). abound in our seas.Similarly, the microscopic world is almost certainly the common ancestor of three major cells.Saul Purton is filled with a wealth of exotic microalgae. However, photosynthetic groups found today: the chlorophytes explainshow this all of these organisms share a common Iegacy - the (green algae and all plants), the rhodophytes (red algae) importantorganelle chlorophyll-containing plastid (= chloroplast) that is and the glaucophytes. The divergent evolution of these evolvedfrom a the site of photosynthesis. This organelle has its three groups from the common ancestor has resulted in photosynthetic ancestral origins as a free-living photosynthetic chloroplasts with different pigment composition and bacterium, bacterium that became entrapped inside a primitive ultrastructure. The chlorophytes have lost the phyco- eukaryotic cell. The bacterium was retained rather bilins, but retained chlorophyll a and /, whereas the red than digested as food and a symbiosis was established algae andglaucophytes have chlorophyll a onIy, together in which the host cell provided a protected and nutrient- with phycobilins. Interestingly, the glaucophytes rich niche in return for the photosynthetic products have also retained the cell wall of the bacterium and generated by the bacterium. The story of how this their chloroplasts are bounded by an inner membrane bacterial endosymbiont evolved into a chloroplast and derived from the bacterial cell, a cell wall of peptido- was then spread by subsequent symbiotic events to glycans and an outer membrane derived from the food other eukaryotes is a fascinating and on-going one vacuole of the eukaryote. In the chlorophytes and that involves the study of a wide range of microbial rhodophytes, the cell wall has been lost and two eukaryotes. membranes surround the chloroplast.

"NColoured slaves N Centralization of power Early in the history of eukaryotic evolution a simple Although the cyanobacterium escaped death by rule applied. Photosynthetic bacteria were the primary digestion, it was to pay a high price for its survival as a producers, utilizing the sun's energy to convert carbon component of the eukaryotic cell. The several thousand dioxide to complex carbohydrates, and single-cell genes the bacterium brought with it, and which allowed eukaryotes were the consumers, often acquiring their food by engulfing and digesting the bacteria or other Phagotrophic eukaryote ! The cyanobacteria (also called blue-green =. eukaryotes. 3 algae) were particularly important producers since CyanobactetirtffiN !) they carried out oxygenic photosynthesis in which I o the harvesting of light energy is coupled to the 3 t q production of molecular oxygen from water. These Greenalgae o 9 early cyanobacteriaprobably contained several different Redalgae (a light-absorbing pigments, including chlorophylls a and Glaucophytes @ b and phycobilins, and could carry out photosynthesis using a wide rz,ngeof light levels and wavelengths. I, Importantly, the cyanobacteria would still be able to photosynthesize even after being incarcerated within the colourless cell of a phagotrophic eukaryote. The (,l o normal fate of the captured bacterial cell would be o o= death by digestion. However, for the eukaryote a CL 0, continuous supply of fixed carbon and oxygen was Chlorarachniophytes---l---..=-- ^\ perhaps an attractive alternative to a quick meal, and Cryptophytes'-J"J o 3 occasionally the death sentence would be commuted q imprisonment. Under this arrangement, the w? o to life 9. RIG HT: bacterium would be allowed to grow and divide within trcleomorph (a $$*.t. Theendosymbiotic I its prison cell, and would therefore be retained and orii'inofchloroplasis, Notethat the Dinoflaqellates ,z4=-->\ chloroplastsofeuglenophytes and inherited by the eukaryote as it itself divided. Indeed, o) dinoflagellatesactually have three examples of such endosymbiotic associations are ffb?:"$",*, @ / Fr rnlannnhrrlac - membranesratherthan four. ltis found amongst modern-day eukaryotes. For example, t-uvrur r\.rPrryLcr analternatitle thoughtthis reflects the cyanobacterium Nostocsurvives inside the cells of feedingmechanism inwhich the t------__-* the filamentous fungus Geosipbonpyriforme. cellmembrane ofthe prey alga is Lossof the Chloroplastreplacement interdependence between Lossof discarded. In one particular case,the photosynthesis chloroplast by furthersymbioses COURTESYS.PURTON the master and his slave became closer and closer over

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'in for food because they could synthesize it house' LEFT: from simple precursors using the power of photo- $$9"S. Transmissron electron micrographsshowing thesimilarity synthesis. However, this meant that the algae also inultrastructure between (a)a became targets for any hungry phagotrophic eukaryote. modern-daycyanobacterium As with the cyanobacterial prey, the engulfed algal (Pseudanabaena)and(b) the plant cells provided new opportunities for the establishment chloroplast(inthis case ina of symbioses, although in this case it was a eukaryote tobaccoleaf) that erl0lrled fr0mthe cyanobacterialendosymbiont. that was being enslaved within a eukaryote (a process PH0T0SDRKARI L0UNAT[/AA (a)AND termed secondary endosymbiosis; see Fig. 1). Once DRJERE[IY BURGESS (b)/SCIENCE again, the endosymbiosis occasionally led to a permanent PHOTOLIBRARY association between the two organisms and the evolution of the captured alga into a bona fide organelle. And BELOW: $$9.S. Lightmicrographs once again the price for survival of the endosymbiont ofvarious microbial eukaryotes was high. Since the only important part of the alga was thatpossess chloroplasts, (a) its chloroplast, other cellular components were rapidly Aglaucophyte (0lau cocysti s),(b) discarded. Consequently, the algal cell was reduced to thered alga Porphyridiun,(c) Euglena,aeLlglenoid algathat it to live an autonomous existence, wefe uncefemon- a chloroplast surrounded by additional membranes obtaineditschloroplast from iously stripped from it leaving only a meagre genome of derived from the algal cell membrane and the vacuolar agreen alga and (d) the a few hundred genes. Genes no longer necessaryfor an membrane of the phagotroph. Remarkably, the nuclear di noflagellate Cerati un IhaI intracellular existence (for example, those required for genes for the biogenesis of the chloroplast were once obtaineditschloroplast motility) were simply discarded. Others were eliminated again moved en masse, this time from the algal nucleus fromared alga. PH0T0S[/IICHAEL ABBEY (a) a process gene in which nuclear to that ofthe new eukaryote host. ASTRID by of substitution & HANNSFRIEDER MICHLER (b) ERIC eukaryotic genes functionally replaced their bacterial Various different algal groups appear to have evolved GRAVE(c)AND LEPUS (d)/SCIENCE counterparts. Finally, and perhaps most remarkably, via this process and include the dinoflagellates, the PHOIOLIBRARY there was a mass transfer of most of the remaining genes euglenophytes, the heterokonts (which include the from the bacterial genome to the eukaryotic nucleus. The diatoms and the brown algae) and the haptophytes (see selectivepressures that drove this gene exodus and the Fig. 3).The chloroplast of the euglenophytes evolved mechanism by which it occurred are poorly understood, from a green alga, whereas the chloroplast of the other but the implications for the evolving chloroplast were groups (with the exception of certain dinoflagellates - profound. First, it had lost control of its own destiny see below) is probably derived from a red alga. In all of since it now possessedonly afractionofthe genes needed for chloroplast biogenesis. The nucleus now controlled the growth and division of the organelle. Second, the expression of those genes that had remained ig the chloroplast (mainly genes for components of the photosynthetic appantus and the organelle's trans- cription/translation apparatus) needed to be tightly co-ordinated with the expression of the nuclear genes that encoded chloroplast components. The nucleus therefore developed elaborate control mechanisms in which nuclear-encoded factors were targeted into the chloroplast to regulate chloroplast gene expression. Finally, the photosynthetic eukaryote had to solve a major logistical problem. The products of the nuclear- encoded genes were now being synthesized outside the chloroplast in the cytosol, whereas previously they had been made inside the organelle. An early modification to the fledgling chloroplast was therefore the development of a protein import system able to recognize the necessary proteins and transport them acrossthe two membranes.

S Frommastertoslave The eukaryotic algae that evolved from the original endosymbiosis had an advantage over their non- photosynthetic kin. They didn't need to go hunting

sN$ffiffiffiw$ffituswToDrvvoL2p,/N)G02 w Further rcading these groups, the old nucleus and all of the cytosolic has attracted considerable interest as a possible target for components have been lost completely. However, in therapeutics, since the parasites' animal hosts certainly Delwiche, C.F.(1999). two other algal groups (the chlorarachniophytes and do not haveplastids. Tracingthe thread ofplastid a vestigial nucleus called the nucleo- through the tapestry the cryptophytes) diversity green of life.AmNat I54, morph remains in the intermembrane space, together WA ancestryf or all? 3164_3I]7. with a genetic system that allows transcription and One of the most contentious suggestions to have translation of the few hundred nucleomorph genes. emerged recently is that the primary endosymbiotic Moreira, D. & Philippe, H. Recent molecular analysis of the nucleomorph genome event occurred much earlier in eukaryotic evolution (2001).Sure facts and open and that many of today's questionsabout the origin and has revealed that it has undergone a remarkable process than currentiy envisaged, evolutionofphotosynthetic of compaction and miniaturization. The nucleomorph eukaryotic microbes have evolved from this plastids.Rer M inobiol152, genes are crammed together on three tiny chromo- photosynthetic ancestor. Limited support for this 111-780. somes, with non-coding DNA, such as introns and has come from phylogenetic studies of various ciliates, minimum. oomycetes and amoeboflagellates, which reveal the Purton, S.(2000). Algal intergenic DNA, reduced to an absolute chloroplasts.In Enclc lopedia The formation of the nucleomorph genome in the presence ofcyanobacterial-like genes in their nuclear ofLife Sciences, a web-based chlorarachniophytes and cryptophytes represents an genomes. Just how fat back we can trace the encyclopediaat www.els.net impressive case of convergent evolution since the photosynthetic ancestof must await further research, 'must two groups have clearly evolved from independent but it is clear that the chloroplast was a have' secondary endosymbiotic events. The chloranchnio- accessoryfor many up-and-coming eukaryotes! phytes have green chloroplasts derived froma chloro- phyte, whereas the cryptophytes obtained their C SaulPurton is a Readerin Molecular Phycology chloroplast from a red alga. Thus chloroplast in the Departmentof Biology, UniversityCollege acquisition by secondary endosymbiosis appears to London,Gower Street,London WCl E 68T UK. have occurred on at least six separate occasions,allowing TeLO20 7679 2675; FaxO2O7679 7096 the emergence of a wide vadety of photosynthetic emaiI s.p urton @u cl.ac. u k eukaryotes. However, it didn't stop there. . .

WAchangeofcolour The dinoflagellates represent perhaps the most fascinating and complicated of all the algal groups. The majority of photosynthetic dinoflagellates probably obtained their chloroplast by secondary endosymbiosis of a red alga. These chloroplasts are distinctive in that they contain the xanthophyll pigment peridinin, which gives a golden colorationto the chloroplast. However, approximately half of all dinoflagellate species have no chloroplast at all and live life as phagotrophs. Others have green chloroplasts that appear to be of green algal descent, and others even have yellow-brown chloroplasts of haptophyte origin (a case of tertiary endosymbiosis!). Recent phylogenetic analysis suggests that all dinoflagellates have evolved from a common ancestor that had a peridinin-containing chloroplast. It would appe^r therefore that the chloroplast has been subsequently lost by some dinoflagellates that reverted to a phagotrophic existence. Others have discarded their original chloroplast in favour of a new one from green algae or haptophytes. A further revelation has come from studies of the apicomplexan protists. These are obligate intracellular parasites and include the causative agents of malaria, toxoplasmosis and many other animal diseases. Remarkably, these organisms also seem to have a photosynthetic ancestry since they possess a non- pigmented plastid with its own tiny circular genome that is clearly a relic of a chloroplast genome, asdescribed in Paul McKean's article on pp. 129-131. This piastid

IE ffiffi $*KSW$SESffiYTODAYVOL2p, / AUGU2 New hope f,orthe neglecteddiseases PaulMcKean

As we enter the 2lst century it is a sobering Clearly there is little financial incentive to develop Thereis an urgent thought that many of the parasitic protozoan drugs against diseases afflicting human populations needto develop diseasesthat were thought to be under control, in some of the world's poorest countries. However, newdrugs against and indeed eradicated from some areasduring the 1960s the dearth of anti-parasite drugs is not just a financial protozoan are again resurgent in many tropical countries. Diseases issue. Our academic understanding of pansite biology parasites. such as malaria, trypanosomiasis and leishmaniasis has often not been at a level adequate for target Paul are once again exerting an enormous toll in terms identification. McKeanexplains of mortality and morbidity on the populations of howgreater developing countries (seeTable i ). Si New opportunities from the distinct understandingof Although there are reasons for this degenerating biology of parasites parasitebiology situation, including complex political and socio- Despitethis rather dismal picture of tropicaldisease and andgenome economic factors (such as military conflicts, collapsing drug development there is now hope thar progress in sequencrng health programmes and population displacement) it is parasite molecular genetics, genome sequencing information clear that the parasites themselves are also fighting back. projects, as well as fundamental studies into the maylead to a There is widespread development of drug resistance biology of parasites, will provide scope for new drug breakthrough. in many parasitic protozoa, a worrying situation for development. diseaseswhere the treatments afe often unsatisfactory Within the next 2-3 years, the genomes of four in the first place. major protozoan pathogens (Plasmodium falciparurn, Although modern medicine has made enormous Leishmania major, Trypanosoma brucei and Trypanlsrma technological advances over the past 40 years, this has cruzi) will be completely sequenced. Careful inter- not been reflected in the field of tropical medicine. For rogation of this wealth of information, allied to a grearer instance, Melarsoprol, the most commonly used understanding of pansite biology is creating exciting drug for the treatment of African trypanosomiasis or new opportunities for the development of novel sleeping sickness, was introduced over 50 years ago. This chemotherapeutics. Nowhere is this approach better arsenicderivative causessevere pain upon intravenous exemplified than by the recenr advances in the injection and actually kills up to lO % of patients identification of new targets for anti-malarial drug due to severeside effects. therapy, based in part on the realization that during its evolutionary history the malarial parasite Plasmodiun 'ate WThe neglected diseases aplant'. Although there is an urgent requirement for the development of new drugs against protozoan parasites, r$i,P1r"-o diu m - a green parasite? these organisms have been largely neglected by Plasmodiurn, along with all other parasites from the pharmaceutical companies in the developed world. phylum Apicomplexa, contains three classesof DNA; At a recent meeting in New York organized by the_ a nuclear genome and two circular DNA elements of French charity M6decins Sans Frontidres (MSF) it 6 and 3t kb in size. It was originally suggested that was emphasized that whilst neaily l,4OO drugs the 35kb element could represent the mitochon- have been introduced over the Iast 2i years, only 13 drial genome of apicomplexan parasites. However, of these were for the treatment of trooical infectious the subsequent identification of the 6 kb DNA diseases. element as the true mitochondrial genome presented kbfie $. Disease statistics associated with several important protozoan pariasites

0isease Parasite Cases Atrisk Malaria Plasnodiunfahipwun 300-500million 2,400million Plasnodiunvivu Pksnodiunnaluiae Plasmodiumwale Leishmaniasis Lenhnaniamajor 12million 350million letshnaniadonovani Leishmanianexicana Leis h n ani ab rasi Ii en si s Americantrypanosomiasis Trypanonnacruzi 1Bmillion 100million Chagasdisease Afticantrypanosomiasis Trypanonnabrucei ganbiense 300,000-500000 60million Sleepingsickness Trypanan mab rucei rhod r;sie nse

Source : Worl d H ealth A rg ani zati on

ir$$*i"ls*$$$**$*s.\-*)-$ToDAyvoL'p,/Auca2w RIGHI: a conundrum. Exactly where within the cell did this $$9.$. Transmission electron 3t kb DNA element reside and what possible function micrographofthe apicomplexan could it serve?Sequencing of the 3t kb DNA element parasiteTox op I asma gon d ii. Ihe that it resembled the plastid genome organellarstructures containing cIeaily indicated thethree genomes ofthis Parasite; of non-photosynthetic algae. Research on a related thenucleus (Nu) mitochondria (M) apicomplex an parasite, Toxoplasma gondi i (an important andapicoplast (..)are indicated opportunistic pathogen in AIDS patients), localized Thegolgi (G) and the anterior (A) the 31kb DNA element to a small membrane-bound andposterior (P)ends ofthe cells nucleus arealso indicated organelle adjacent to the apical end of the PHOTOCOURTESY PROFESSOR DAVID (Fig. 1). This structure, a relic chloroplast-like plastid ROOS,DEPARTMENT OFBIOLOGY termed the apicoplast, appears to have been acquired OFPENNSYLVAN IA UNIVERSIIY progenitor of the apicomplexan phyla PHILADELPHIA,USA by an early through a process of secondary endosymbiosis. It is conserved OPPOSITEPAGE: proposed that aprogenitor algal cell initially engulfed bipartite apicoplast targeting signal is well rfliqsII" Schematic showing a cyanobacterial-like prokaryotic cell in a primary phylogenetically, enabling nuclear-encoded apicoplast apicoplastmetabolic pathwaYs endosymbiotic event (see Saul Purton's article on pp' proteins to be identified from the P. falciparum genome Biosyntheticpathways within the I25-I28 for the development of chloroplasts in algae). sequencing project solely on the basis of primary apicoplastaredependent upon information (seebelow). pyruvate.Ihisis acquired through The subsequent engulfment of this algal cell by the sequence theimport ofsugars and/or apicomplexan ancestor (secondary endosymbiosis) and - phosphoenolpyruvate andthe the subsequent retention of the plastid gave rise to lx.1.:'Theapicoplast the enemywithin! enzYme subsequentactivity ofthe the apicoplast. Nfhiist the unusualevolutionary history and cell pyruvatekinase Isoprenoids are to appreciate that the apicoplast (and biology of the apicoplast is clearly a fascinating area synthesizedviathe D0XP- It is important relevance of the dependentpathway andare indeed all plastids) retain a considerable degree of of academic research, the functional requiredforthe isoprenylation of autonomy despite their intracellular existence within apicoplast was initially obscure. However, the fact tRNAsand possibly other metabolic eukaryotic cells. This autonomy extends not only to that apicomplexan cells had retained this organelle functionswithin the cell Acetyl retaining their own reduced genome' but also to the over millions of years of evolution strongly argued that CoAisproduced frompyruvate it may have avital cellular role. The precise nature of bythe action ofa pyruvate retention of transcription and translation systems dehydrogenasecomplexand used that arc fundamentally prokaryotic in nature. this is at last beginning to be unravelled, partly as a toproduce fatty acids via acetYl result of information derived from genome sequencing CoAcarboxylase anda type ll FAS ,$*l'Apicoplast genes a nd protei ns projects. Significantly, apicoplast metabolic pathways complex.Although notdiscussed the plastid genome ftom Plasmodium are more characteristic of bacteila and plants than inthe text it is also likely that Sequencing of of thebiosynthesis ofhaem isa and Toxoplasma rcvealed that many apicoplast genes animal cells. Obviously the cyanobacterial origin metabolicfunction ofthe were exclusively involved in gene expression, including the apicoplast now takes on added importance, as apicoplast. Iarge and small subunit rRNAs, 25 species of IRNA, pathways fundamentally different from mammalian [/lCKEAN DIASRA[/COURTESY P subunits of eubacterial RNA polymerases and the cells provide excellent targets for the design of new (BASEDONA FIGURE BYPROFESSOR DAVIDROOS DEPART[/IENT Ot translation elongation factor Tu. The presence of parasiticidal drugs. BIOLOGYUNIVERSITY OF prokaryotic-like proteins explains the susceptibility PENNSYLVANIAPHILADELPHIA USA) - of apicomplexan parasites to antibiotics that interfere l{il\Apicoplast metabol ic pathways the with bacterial transcription and translation, such as Ach illes heel of apicomplexa n parasites? rifampicin, erythromycin and doxycycline. lserpr*n*idhi*synthe*ia. Isoprenoids represent a However many apicoplast-specific genes (probably remarkablydiverse group of essentiallipids that include more than 100) have also been transferred lateraily to cholesterol and the respiratory chain electron caniet, the nuclear genome of the apicomplexan cell. The coenzyme Q (ubiquinone). Isoprenoid synthesis depends targeting ofnuclear-encoded proteins to the apicoplast upon the production of a citical subunit, isopentyl presents a complex problem for cells as the apicoplast diphosphate (See FiS. 2). Synthesis of isopentyl is surrounded by four membranes, reflecting the diphosphate can proceed via two distinct routes, the two endosymbiotic events leading to its formation. melavonate-dependent pathway and the melavonate- Toxop/asmahas been instrumental in the elucidation of independent pathway. apicoplast-targeting sequencesdue to the exceptional In mammals and fungi, isopentyl diphosphate is ultrastructure of these cells. These studies demonstrate synthesized by the melavonate pathway, whereas in that nuclear-encoded apicoplast proteins encode an eubacteria, plants and algae this critical subunit is amino-terminal bipartite targeting signal. This consists synthesized by the melavonate-independent or 1-deoxy- of a typical amino-terminal secretory signal sequence D-xylulose )-phosphate (DOXP) pathway. Significantly, immediately followed by a plastid-targeting domain. inhibitors of the melavonate pathway are ineffective These two domains together are sufficient to target as antimalarials, indicating that this pathway is absent proteins with great efficiency to the apicoplast. The in Plasmodiam. However, two key enzymes in the

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not surprising therefore that the type II FAS pathway Triosephosphate Furtherrcading has recently been identified in P lasmodium. and/orphosphoenol \WebsiteofM 1decinsSant Crucially the two FAS pathways differ in F rontiDres,the independent (a susceptibility to inhibition by the drug triclosan humanitarian medical charity: broad-spectrum antibiotic); the type I FAS pathway is http://www.msf.org/ rcfractory, but the type II FAS pathway is inhibited. Ralph, S.A., D'Ombrain, Administration of triclosan to malaria-infected mice M.C. &McFadden,G.I. results in the parasites compiete clearance of malarial (2001).The apicoplastas with no adverseeffect on the mammalian nost. an antimalarial drug target. Pyruvatekinase One of the major attractions of the apicoplast as a DrugRairt Updates4, H;;; / drug target is its prokaryotic character. This is not solely r45-r5l. / -, biosynthesis J,- because apicoplast biochemistry is fundamentally Roos, D.S., Crawford, different from that of the mammalian host, but also Pyruvate------+ AcetylCoA MJ.,Donald,R.G.K., because considerable investment in antibacterial PyruvateDH Fraunholz, M., Harb, O.S., complex drug development now provides a pre-existing source He, C.Y., Kissinger,J.C., of inhibitors that may be effective as anti-malaial Shaw, M.K. & Striepen, B. drugs. (2002).Mining the ri"pr"r"iJr rattvacio ; i Unfortunately, trypanosomes and Leishmania do P lasmodiurn genomedatabase to defineorganellar function: ;b1o1vn!hes1s,lb1o9vlthesls, not harbour an apicoplast-like organelle to target for ltl what doesthe apicoplastdo? chemotherapy. However, with these pathogens roo DOXF AcetylCoA PbilosTrans RSoc Lond B 357 , there is renewed optimism that the wealth of 3546. Typell information from genome sequencing projects, allied V Singh,D. lsoprenyltRNA FAS to greater understanding of parasite biology will lead &Habib, S. (2000).Theplastid in to better target identification and ultimately to the Apicorupkxa:genome, development of new and desperately needed drugs. function and evolution.rl ParasitDis 24,18. O Dr PaulG. McKeanis a Lecturerin the Departmentof Biological Sciences,Lancaster $/ilson,RJ.M. & (1997 University,Lancaster, Lancashire LAI 4YQ, UK. $/illiamson, D.H. ). ExtrachromosomalDNA in DOXP pathway have been identified in the Plasrnodiunt Tel.01524 594717 the Ap icomplexa. Microbi oI Mol genome; DOXP synthase and DOXP reducto- em ai I p.m ckean @l an caster.ac.uk BiolReu6l.146. isomerase. The apicoplast localization of these two enzymes was strongly indicated by the presence of the bipartite apicoplast targeting sequence at ther amino terminus. Although the exact role of isoprenoid biosynthesis is still under investigation (as it is likely that Plasmodium salvages cholesterol from the host cell), this path- way is unquestionably important to Plasrnodiurn. For instance, mice infected with the rodent malarialparasite Plasmodium uinckei can be completely cured of their infection by the administration of the antibacterial drug fosidomycin (an inhibitor of DOXP reducto- isomerase.

Fatty acid synthesis. The synthesis of fatty acids, which are important for cell growth, differentiation and general cellular homeostasis, represents one of the most critical biochemical pathways within cells. Fatty acids are synthesized de nouoby most organisms, with two distinct types of fatty acid synthase (FAS) being described to date. Type I FAS is typically found in the cytosol of most eukaryotic cells, including man. Although the type II FAS pathway is widespread in bacteria, in eukaryotic cells it is almost exclusively limited to those organisms containing plastids. It is

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'Eschericbia As an undergraduateonce observed, bearing a four-cysteine zinc finger structure, that binds Fungican -GATA-. metabolizea coli d.oesn'tbaue a uerywell deuelopedneruous system' to DNA regionswith the coresequence This is and the samegoes for fungi and most other a member of a family of regulatory proteins, now called widerange of GATA factors, which are not restricted to fungi, but but micro-organisms.However, they arevery accomplished compounds, at observing their environment and making appropriate are found throughout eukaryotes controlling many whena variety decisions;an ability which puts many a human to shame. activities.One of the best-characterizedis GATA-1, one isavailable a \7e often find it difficult to know what to eat, and a long of the six vertebrate GATA factors, and it has a major sophisticated menu cancause agonizingdifficulties. I havea sisterwho role in controlling globin geneexpression for blood. In controlsystem takesat least 10 minutes to come up with an answerif fungi there are several GATA factors involved in determinesthe you askher what shewould like to drink- This contrasts regulating processesfrom sexual development to orderin which they with the averagefungal mould that showsa surprising circadianrhythm. The first of theseto be characterized willbe used. abllity to both consumewhat seemsunpalatable and wasareA. Seminalwork published in 1973 definedthe to do so in an impressivelyorderly fashion. At the role of this Aspergillus nidulans gene as a regulator of beginning ofthe 1960sthe Frenchscientists FranEois geneexpression. It is required for the expressionof the in the utilization of nitrogen Jacob and JacquesMonod described such a decision- many genesinvolved making mechanism in bacteria.'I'll eat up lny glucose sources other than ammonium and glutamine' beforetucking into the lactose'is the lessonthat every self- Mutations inactivatin g areA prevent the fungus from respecting bacterium and undergraduate has learnt. using most nitrogen sourcesother than ammonium and Their classic work gave us the lac operon, which glutamine. A seriesof papers defined areA as a gene illustrated how gene expressioncan be switched on that encodeda protein which actsdirectly on promoters and off through the interaction of regulatory proteins ofthe structural genesneeded for using lessfavoured (transcription factors) with a region of DNA (the nitrogen sourcesto regulatetheir transcription.It is a promoter)just infront ofthe DNA that encodesaprotein tribute to the power of genetic analysisthat many of the (the structural gene).Soon afterwards came descriptions detailed conclusionsrelating to this gene haveproved of similar regulatory systems in fungi and other correct.Our fundamental understandingof the system eukaryotes. remainslargely unaltered eventhough the genehas been Among the best-charactefizedsystems are those cloned,well over 100 mutations sequencedwithin it, regulating nitrogen and carbon metabolism. Fungi the structureof its DNA-binding domain definedat the are the champions among scavengersand the key to atomic level and the characteristicsof its binding this is their metabolicversatility that in turn requires abilitiesanalysed. sophisticated control. In the mid-1960s the first The areA gene produces a protein (AreA) whose observationswere made of what is now called nitrogen activity is itself defined by severalsignalling mech- metabolite,or ammonium, repression.This determines anismsthat report which nitrogen sourcesare out there. that if a good nitrogen'source' such as ammonium Among theseis a protein, NmrA, which in the Presence or glutamine, is present then it will be utilized of high levelsof intracellular glutamine repressesAreA preferentially. Consequently,the genesand enzymes activity. This repressioninvolves interactions with both required for the metabolism of lessfavoured compounds the C terminus of the protein and its DNA-binding such as nitrate, acetamide,purines and various amino domain. A secondmechanism modulates the amount acidsarc allturned off. This regulation hasconsiderable subtlety; it is not just a simple on/off switch. The order of genesbeing turned on as the nitrogen is steadilydepleted seems to be defined. I7ithin this hierarchysome genes are only expressedunder nitrogen-starved condi- tions and others are only repressedif high levels of ammonium or gluta- mine arepresent. RIGHT: Nitrogenrsgulati0n inAspergillus Sohow is this achieved? nidulans, In most fungi it involves COURTESYM.CADDICK a transcription factor,

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motif, but so do at least five other proteins, so how LEFT: JN is functional fidelity retained? Perhaps most impom- Aninduction time-course ofGFP ffi BXpressi0ninArabi dopsis thal ian a, antly we don't know all the activities that are regulated Two4-week-old soil-grown a/cR by AreA. AreA regulates nitrogen metabolism in alcA'.'.GFPplants were monitored A. nidulans, but this system appears to have additional byfluorescence microscopy overa roles in other fungi, such as regulating genes involved 47hour period after induction by in pathogenicity, toxin production and antibiotic rootdrenching with 1 % ethanol. ar@ COURIESYJ.DOONAN M synthesis. The AreA regulatory system is not the whole story for nitrogen metabolism, In either. some BELOW: single-celled yeasts, for example, nitrogen limitation Asperg ill us n i dulans growth tests. leads to a morphological switch, so that the cells change Awealth ofdata can be obtained shape to something much more like conventional fromsimple plate tests. Inthis fungal hyphae. This is very important in pathogenicity, examplearange 0f different strains arebeing tested for their ability to E M particularly in animal pathogens such as Candida utilizedifferent nitr0gen s0urces as albicans.Shape-changing is triggered by various signals, wellas their resistance totoxic but its regulation does not apparently involve areA analogues,Abbreviations: 0rn, homologues. \When it comes down to it, nitrogen is not ornithine;Pyr, 2-pyrrolidone; Asp, merely a nutrient, but is also an environmental marker asparagine;Arg,arginine; GABA, 23h T-amino-n-butyrate; Gly,glycine ; W that affects the fundamental biology of anorganism. AHtL-13-aspartyl-hydroxamate In addition to global regulatory sysrems like REPRODUCEDWITHPERMISSION areA, most metabolic pathways have a second level FRO[/CADDTCK ETAL (1997) GENESANDFUNtTt0N 1 37-49 (O of regulation, asking whether a specific substrate is PORTLANDPRESSLTD BLACKWELL available. It is a bit like seeing what is in the fridge, and SCIENCELTDTHE GENETICAL SOCIETY -rr@ @ then deciding what you prefer. Many genes regulated ANDTHE PHYSIOLOOICAL SOCIETY) ofactive AreA protein in the cell by altering the stability by nitrogen metabolite repression require this of the RNA message directing its synthesis such that second signal, so that only the presence of the specific it degrades rapidly if glutamine is present. These and substrate in addition to the absenceofa betrer nitrogen other signalling mechanisms are actively monitoring source lead to their expression. Carbon metabolism also the nitrogen levels within the cell and combine to define has a similar hierarchy of regulatory devices. In fungi, the level ofactive AreA. \7hen it is active, AreA moves to proteins from the zinc binuclear cluster family of the nucleus where it can bind to promoters and facilitate DNA-binding proteins often do this job, regulating gene expression. The affinity of AreA for promoters transcription of genes required to deal with a specific defines a hierarchy of gene expression. Critically, the carbon soufce. promoters of the genes it regulates have differing, A good example is the A. nidalans transcription affinities for AreA, so when there are low levels of factor AlcR that is responsible for regulating alcohol AreA within the nucleus only genes with high affinity metabolism. It interacts with the promoters of genes, will be activated,while in n _.__r._.__ uenolype Nitrogensource AH Chlorate severe nitrogen shortages AreA levels increase and NHi Orn Pyr NO; NOt Arp Urea Arg GABA Gly 0.25 2,00 100 500 most of the genes within its regulatory domain can be areA+ switched on. Consequently, the genes that can utilize areA::C the preferred nitrogen sourcesare turned on first. areA:: NC As with much of science there are always more areA::CN questions than answers. Forexample,we now know areA::AC that multiple signalling systemsare involved, but areA::NxC we don't know most of their components or how areA::AxC they perceive nitrogen. \7e know AreA binds to DNA areA' td sequenceswith the GATA

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i. hke alcA, needed to deal with ethanol, switching them on when alcohol is around. S7e have used AlcR to make a switch for genes in plants that is completely under the control of researchers. This works because the gene transcription machinery is conserved among eukaryotes, so that this regulatory protein functions in plants as well as fungi. Conventional genetic engineering techniques let us arrange for continuous production of AlcR within plants such asArabidopsis thaliana-Then, provided agene had an AlcR-regulated promoter, it would be expressed whenever alcohol was present. Of course, plants do not usually have this sort of promoter, which is precisely the reason for devising this switch. So, all you have to do is change the promoter of gene you are interested in, through some more genetic engineering, and then you can switch it on by watering with ethanol. The fact that the system can be transferred directly from fungi to plants suggests that AlcR detects the chemical signal directly, and there is no genetic evidence to suggest otherwise. The net result is that we now have an effective plant gene switch that allows transient expression of genes in a very well controlled manner - just water yourplants with alcohol! So in fungi we have regulatory systems that operate very much like animal and plant systems, providing fantastic model systems for experimentation. The biology they regulate is also important, whether you are interested in avoiding toxins, producing antibiotics or not getting a fungal disease.And finally we can put the expression systems into other organisms, whether we want to change the way they grow or, more often, simply try to understand how theywork.

O Dr MarkX. Caddickrs SeniorLecturer,Schoo/ of Biological Sciences,University of Liverpool, Liverpool L69 7ZD, UK. emaiI caddick@l iv.ac. u k we b s i te www. Ii v.ac. u H - sd 2 1/ n it rog en / i n d ex.htm

lm NS$SNSNS*SNNTODAYVOL29/AUG02 Survival by cAM P in social amoebael an intersection behnrceneukaryoteand prckaryote signalling systems PaulineSch aap

@- Dictyosteliumhas a ffi Sporulation is a common strategy for most fascinatingstrategy ffi";okaryotic and eukaryotic microbes to fordisseminating Wil",i"Jr""i shortage and other environmental itsspores to ensure challenges. This essential responseensures the long-term survival of microbes in a quiescent state until conditions survival,Pauline that are suitable for growth resume. Typically, sporu- Schaapdescribes lation involves the active elimination of water from the thesophisticated cell, cessation ofmetabolism and finally encapsulation in systemof cell a protective cell wall. The process is remarkably effective communication as shown by the recent discovery and subsequent thatenables this to germination of spores that had been preserved in amber happen, for millions ofyears. Most spores do not need to wait millions of years for their environments to improve, and growth resumes Swelling Emergence predictably in a short amount of time. Some other passively waiting around, tip the microbes, rather than Qn scalesin their favour by placing their spores in locations PDET{'-7 that will allow their transport to better pastures. One of -1r/ . __:::= the most elaborate and magnificent examples of this lc/l/ AMPII V" latter strategy is seen in the social amoeba, Dictyostelium discoidearn.These single-celled soil inhabitants first n IfcAMP Ita get together when food runs out. Up to 100,000 r -! Gi-rl . \-/ tlilflt independent cells then collaborate to build a fruiting At-A l- llllill FrvFr I llfltll body that keeps the spores aloft and facilitates their llrlrll: lltrtt dispersal by insects and other soil creatures. A - system for cell-cell communication ,^. sophisticated /\ has evolved to co-ordinate the functions, such as *l metabolism, movement and differentiation, that allow BELOW: @@ ,:::r1. 11'trDictyosteliunlile fruiting body formation to occur. cAMP, a well known cycle mediator of hormone action in vertebrate cells, plays a for fruiting body formation. Meanwhile, the cells start crucial role at almost every stage of the sporulation to differentiate. About 7 5 % of the cells express genes TOPRIGHT: pfocess. that will ultimately cause them to transform into spores ,:i!:",i . Regulationofspore fated to The remaining 25 express genes that germination survive. 7o ,:i,:Extracellu lar cAM P will cause their transformation into the stalk cells that Ar BOTTOMRIGHT: In the first stage, the starving amoebae use cAMP as are doomed to die. At first the two cell types are :rir:. I .\.Adenylylcyclase Ais a chemoattractant. Some cells start to secfete a pulse intermixed, but when slugs start to form, they sort out. I bypositive and negative I regulated of cAMP every 6 minutes. The cAMP pulse induces The prestalk cells (blue in Fig. 1) move forwards to the feedbackloops a{ surrounding cells to move towards the source of the front of the slug, while the prespore cells (red) remain at o DIAGRA[/SCOURTESY PSCHAAP signal and to secrete a cAMP pulse themselves. As a the back. ( '@$ result, waves of cAMP During fruiting body formation, the prestalk cells at : n propagate through the the front synthesize a central cellulose tube and then field of starving cells, move into it. \While doing so they differentiate into ,@.. which move collectively stalk cells. This is quite a dramatic process; the cells a-q towards each other to form swell by taking up water and deposit a shared layer of a multicellular aggregate cellulose fibres that allows them to assemble into a rigid d- I t (Fig. 1). stalk. The prespore cells move up the stalk. They mature A Fruitinobodv formation Sporegermination The aggreg te then into spores by losing water and by constructing a thick \ undergoes incriguing wall from prepackaged spore coat materials. cAMP oscillations shape changes. A small The cell movements that allow slugs and fruiting Migratingslug extrusion, the tip, appears, bodies to form are controlled by the tip cells. They Hrc ',,, which extends into a continue to secrete cAMP pulses, which travel through finger-shaped structure, the slug in waves and causecells to move towards the tip. the slug. The slug topples The cAMP waves also cause the prestalk and prespore ffiw6-ffi;:over and migrates towards cells to sort, because the prespore cells gradually lose the light until it reaches chemotactic responsivenessto cAMP andarc left behind a location that is suitable to occupy the rear ofthe slug. ExtracellularcAMP hasa secondimportant function: (FiS.2).In the fruiting body, spores are kept dormant it inducesthe differentiation of the presporecells. The by the presence of a plant cytokine type molecule, presporecells in turn secretea small lipophilic facror, discadenine, and by high osmolarity, which is also a DIE that inducesthe differentiationof the stalk cells. common inhibitor of the germination of plant seeds and fungal spores. Young spores require a stimulus such S IntracellularcAMP as food to germinate. Old spores secrete an autoactivator Social amoebaeare the only known organisms that of germination and germinate in the absence of any usecAMP asan extracellular signal. Most prokaryotes stimuli. After being activated for germination, spores and eukaryotesuse cAMP asan intracellular messenger enter a lag phase before swelling and emergence are for a wide variety of physical and chemical external initiated. During the lag phase, spores sensewhether stimuli. In prokaryotescAMP is usually detectedby the environment is suitable for germination, and if not, transcription factors,such as the cataboliterepressor they return to dormancy. High osmolarity is also a protein. In eukaryotesthe mosr common targer is constraint factor that induces rerurn to dormancy and the cAMP-dependent protein kinase (PKA). In it does so by increasing intracellular cAMP.

TOPLFFT: High WAdenylyl cyclases osmciarity $ig.$, Adenylyl Dictyostelium cyclaseGis an cells express three adenylyl cyclases that 0smosens0rthatcontrols spore synthesize cAMP from ATP. Adenylyl cyclaseA (ACA) is germinati0n regulated by a positive and negative feedback loop to produce the cAMP pulses that control cell movement. BOTTO[/lLEFT: $'ilt. $" RegAand This works as follows: starving cells secrete a ACBcontrolthe small maturationofspores. amount of cAMP, which acts on surface cAMP receprors (cARs) to stimulate ACA activity and initiate a cAMP DIAGRAMSCOURTESY PSCHAAP pulse (Fig. 3). \)fith a small delay, extracellular cAMP also triggers an inhibitory pathway that blocks further activation of ACA. An extracellular phosphodiesterase then degrades cAMP. cAMP receptors are now freed from cAMP and the cells become resensitized to respond tocAMPoncemore. Adenylyl cyclase A (ACA) is homologous to rhe vertebrate adenylyl cyclases.These enzymes harbour two sets of six transmembrane domains interspersed with two catalytic domains. They are regulated by serpentine receptors that are coupled to heterotrimeric G-proteins. In vertebrates the B-adrenergic recepror, coupled to rhe G-protein Gs is the archetypal example of a signalling pathway that via acrivation of an adenylyl cyclase and PKA leads to glucose production. Glucose is required I f r flr r for the so-called fight or flight response that is triggered t al by an increase in blood adrenalin levels. In Dictyosteliurn, the serpentine cAMP receptors acrivare the G-protein (Fig.3). Adenylyl cyclase B (ACB) produces the intracellular cAMP for spore maturarion. The ACB gene is homo- Iogous to that ofadenylyl cyclasesin cyanobacteria. In addition to the cyclase catalytic domain, it harbours a response regulator and a histidine kinase domain. These are very common components of the phosphorelay signal Dictyostelium,intracellular cAMP acring on PKA induces transduction systems in prokaryotes. The significance the maturation of spore cells. Intracellular cAMP also of these regions for regulation of ACB enzyme activity regulates the very first step in the life cycle, the is not yet clear. germination of the spores. Germination is a critical Adenylyl cyclaseG (ACG) controls spore germination step in the life of any organism with a dormant phase, GiS. q. It is structurally homologous to adenylyl suchas a cyst, spore or seed, because it must only occur cyclases inTrypanosoma pansites with a single catalytic under conditions that allow proliferation. Several domain and a single transmembrane domain. ACG is constraints regulate spore germination in Dictyostelium strongly stimulated by high osmolarity. It produces

$s$sNs$ffi$sils$sw roDAy voLn / AUc02wl cAMP which activatesPKA. PKA in turn blocks the transitionfrom dormancyto germination.

WPhosphodiesterases The phosphodiesterases (PDEs) that degrade cAMP are of crucial importance for every step in the life cycle. PDE is an extracellular enzyme that degrades cAMP between pulses. This is necessaryto generate steep gradients of the chemoattractant and to resensitize the cells for the next cAMPpulse. RegA is an intracellular cAMP phosphodiesterase; its vertebrate-like phosphodiesterase domain is activated by its prokaryote-like response regulator domain. RegA acts antagonistically with ACB to control the process of spore maturation (Fig. 5). In migrating slugs, spore maturation is inhibited by ammonia which is produced in large amounts as an end product of protein degra- dation. Ammonia is detected by the histidine kinase dHKC. dHKC initiates a chain of events in which phosphate is first carried over to an intermediate, RdeA, and subsequently to the response regulator of RegA. RegA is then activated to degrade cAMP, which is continuously being produced by ACB. \fhen the spores are carried aloft during fruiting body formation, ammonia will be removed by diffusion into the atmosphere. dHKC, and therefore RegA, become inactive. At this point cAMP can accumulate and activate PKA. PKA triggers the expression of spore genes and mature spores are formed shortly afterwards. In essence the function of cAMP during Dictyosteliurn development is to bring starving cells to the spore stage and to maintain dormancy until conditions improve. Signalling strategies from both the prokaryote and eukaryote kingdoms have been united to perform this unique feat of self-o r ganization.

O PaulineSchaap is Readerin the School of Life Sciences,Universityof Dundee, MSI(WTB Complex,Dow Street,Dundee DDI 5EH, UK. Tel.01382348078: FaxO1382 345386 emai I p. schaap @d u ndee.ac. uk SGM prim ary_schoolGompetiHon : mffiwwwfuww* ffifrerxd ffitr #me?

SG M' World of MictobC pack The competitionwas organizedto markthe launch BTLOW: of the SGM packfor primaryschools, The Worldof Winningentries inthe S0M primary Copiesof the packare available from Microbes.ltis a requirementfor all pupilsat Key Stage schoolcompetition. Iop:1st prize, theSG M EducationOffice, price S 15 inc. 2 to studymicro-organisms underthe section LaurenMeader. Middle:2nd prize, 'Living TristanGoodfellow. Bottom : 3rd p& p,Email [email protected] thingsin their environment'as laid down in the for NationalCurriculum for scienceSC25f. They have to prize,Chloe Varon. Seetext furtherinformation. betaughtthat micro-organisms are living organisms forfull details. that are often too smallto be seen,and thatthey may be beneficialor harmful.'Unit6B Micro-organisms' from the primaryscience schemes of work puts togethera suggestedformat to show how SC25f may be addressed.TheWorldof Microbeshasbeen written foryears5,/6 and supportsthe deliveryof this unit.The childrenwere invitedto producean attractiveA3-sized posterwhichshowed the harmfuland beneficialroles that microbesplay in our lives,suitable for displayin the schoollibrary. Over400 entrieswere receivedfrom schoolslocated acrossthe wholeUK, including Northern lreland. Judging,carried out by a panelofmicrobiology educationexperts guided by DarielBurdass, SGM Education Projects Ad mi n i strato I was extrem e ly difficult.Adjudication took accountof originality, scientificcontent and accuracy,presentation and the effectivenessof the posteras a meansof communicatingwith the peergroup. Considering that manyprimary school teachers have no scientific trainingand microbiology is quite a specialistdiscipline whichlabours under the considerabledisadvantaoe that the subjectto be taught is invisible,the standird of entrieswas remarkablyhigh. K@WE5 The postercompetition provided the teacherswith an excellentassessment opportunity. The judges were particularlypleased to see that some pupilsdid notjustfocuson the roleof micro-organismsin food productionand disease. The more successful entries coveredthe importantrole that microbesplay in decay, bothbeneficial, e.g. composting, and harmful, e.g. food spoilage,as wellas the roleof micro-organismsin the productionof medicine. Thefirst prize of g1 50 forthe schoolwas won by Lauren Meader, aged B,of the AbbeySchool, Reading.Her classwill also have an outingto a localscience centre, The secondprize of S75 went toTFistan Goodfellow, aged 9, of Dulwich CollegePrep School and the third prizewas won by Chloe Varon, aged 10 of St Paui'sJunior Schooi, Kingstonupon Thames, Each winning pupilreceived a booktoken. Several otherentries were highlycommended or commendedand received specialcertificates. Everyschool entering the competitionreceived a Worldof Microbesoack andeach pupilwas sent a certificateof entrv,

i:iill{;::\\i:i.;\.*\$$;}ii.{\S\N"^IODAYVOL2g/AUG02Im Equalopportunities in microbiology researchGareer? LizSockett

SGM Education At the \Warwick SGM Meeting in April the OfficerLiz Sockett External Relations Staff and Education Group exploressome pur together a very successfulcareers evening currentequal for postdocs and graduate srudenrs. At the reception oppodunityissues after the event I asked for comments from attendees as to what other information whichaffect careers they would like. I was quickly surrounded by a group who requested everyonetraining more information on how women can build successful andworking in research careers and whether family considerations microbiology,Further causeproblems. I promised I'd publicize supportive contributionsfrom schemes that are avarlable.In addition,I wanr to take reaOerson any the opportunity here to flag up two other equal aspectof this topic opportunities issues: encouraging more people from arewelcome, Tell us diverse ethnic groups to take up researchcareefs and the whatyouthinkl impact that the recent extension to the Disability Discrimination Act will have on people with disabilities Lizmaybe contacted entering university, studying for first and higher degrees atGenetics Division, in microbiology and going on ro researchcareers. I do not Schoolof Clinical write as a professional in equal opportunities, bur as a LaboratorySciences, committed enthusiast for equality of opportunity for all, Oueen'sMedical and as a female microbiology academic being a member School,University ofa minority group myself. of Nottingham, All microbiologists enjoy finding out about the massive diversity '.i, Nottingham in the microbial world and we celebrate ,, :;,,,.,,,:;:,II:rl:::rr::.: -, :;:,,,,:,:,,-,. ShOUld be a fifStpOft in our publications bugs with amazing and different NG72UH,UK of call, they should have an equal opportunities policy capabilities. $fhile it is true that rhe average under- 'Personnel' (Te|,01159194496; which you can usually find on the web pages. graduate microbiology class in the UK will contain -r,;1:, :i.i.' 'thg ; .i..ir:.:.ir:.:::1:,,r,,;,. aims fOf adUancenentOf emailliz,sockett@ about 50:50 women to men, members of minority wzmen in scienceenginuring and technology(SET) in Higher nottingham.ac,uk), gforlps are underrepresented (compared to numbers in E ducat i on'. Its websi re, http :,/,/www.ath e n a,i c. a c.uk/, has the whole population). Ar present it is also very rare ro details of its mentoring schemesfor women postdocs and have a student with a physical disabiliry in a micro- young academics, discussion gfoups and conferencesand biology degree class.Moving up through PhD to post- a useful links page to other resources. doc and academic posts in microbiology and other

:!.:,,..,,.,,, biosciences,the trend is towards a higher and higher ,,,,': ,' ,',,.t::.i.,;:-;,..',, .-,l-.:::-:t:: il.,-,a:,l;,.,1.,.i.,i: pefcentage of white males in senior researchposts. Now ,:r,-:;,,;,:,,,,,;,', ,(10 pef yeaf, 4years funding each)are for I have absolutely nothing against white males, being research in natural sciences,offering the kind ofsupporr happily married ro one myself, but recent equal and flexibility which are particularly beneficial for opportunities policies aim to ensure that ail members female scientists(also open to men). of society afe encouraged and have access ro cafeer http :,//www, royal soc.ac.u k,/f u n d in g /f e || o_d h f ,htm opportunities in all walks oflife, including microbiology. r',:..:1,.r;,r.i!:'.:.::l:t...:::r--:::iir:.:,,i,whosgmissionis'retarning ,'.,Schemes to help womenscientists engineersand scientists to tuork after career breaki , also offers in researchcareers (and for menraising postdoctoral fellowships for women and men who have fam il ies/ca ring for relatives) taken a careet break of at least 3 years ro care for family members. The fellowships include an elemenr of Although in 1998 50% of undergraduates were female, retraining to update skills where required. Several of rhe but only 9 %owere professors, things are changing and fellowships are sponsored by agencies(BBSRC, NERC, there are now schemes and policies that help youflger Leverhulme Trusr, etc.) that typically fund microbiology women combine a careerand have a family. Some of these research as part of their contributions to female-friendly are listed here and I hope that the information will be of oolicies. use in careerplanning. The messageI'm trying to give is http:/,/www.sst. ph.i c.ac. uk/trust/i ndex.htm I that things are improving for the better and new schemes

and opportunities are conrinually being developed. ,'-,!,:t,1...,,,--r;,...--..,,,,:lt',.,:.,,1-.,.t:.,,t:li.r:.:,,:,...-.::,-l:.ri:::=l.,,ti:::1, Eventually these will filter down to change the ethos of has recently published a position paper on working the workplace, including the way that maternity leave together to achieveequal represenrarionof men and and career breaks are viewed. If you're a woman micro- womenin the life sciences;seehttp:,//www.embo.org/ biology student or postdoc, get online and get informed. projects/wome n/wo me n_pos ition*paper, pdf . They

IM .:::i..r::.:rr::''lli:,:lii.l::'''l:11,,,i...1.,,..,.r't,;'''llQl)[fVOL29/AUG02 also have a range of research fellowships with flexible policies and career restarts after family breaks. can be fbr-rndon the follorving website, but check your http :,/,/www.em b o.o rg / p ro1e cts/wo m e n/i n d ex.htm I own institution's web pagesfor a digest of what it means to yolr. '\7omen has a in Biology http://www.parl iament.the-stationery-office.co.u k/ \Working Gror,rp'(\fIB\7G) and has aiso just appointed pal|d200001/ldbills/01 B/01 01 B-e.htm# its first female president, Dr Nancy Lane, an active promoter ofwomen in science. The STIR\7G is trying to : The National Br-rreaufor Students with Disabilities promote activities that sr-rpportwomen scientists in the hasatl v ice l-orat'adem rcs on irssire. UK and can be contacted at ruth.tittensor@faenol. www.skill.org.uk freeserve.co.uk , an affilatecl organization to LTSN, provides Changesto the Disability Discrimination resolrrcesancl advice on technologies and methocls that Act to encouragestudents with disabilities make teachingaccessible to studentswith disabilities.

into highereducation ""Y"',hIIo:/ / | er-hdis ac.rrkl From September 2002 the 791)5 Act incorporates the 'Special Edr-rcationalNeeds and Disability Act'. This will work on behalf of HEFCE t ,9 1 make it r-rnlawful for higher education instirutions to enhancedisability provision. Lr{' d to treat students and applicants for degree collrses http :/,/www.n aid isteam . ac.uk/ Iessfavourably than someone else for a reasonrelated to fi their disability without jr-rstifrcation.This change will Dr Liz Sockeff,SGM EducationOfficer. I encouragemore students wirh disabilities into higher {'u education and puts rhe onus on institutions to make P|]OTOSGI/ reasonableadjustments to their teaching methods to ensurethat such applicants or stndents are not placeclat a substantial disadvanrage in comparison to someone who is not disabled. In the microbiology arena this can mean adaptation of practical classesfor students with visuralor pl-rysical disabilitiesancl in lecturestl-re provision of information in new media, including tapes, cliscsor large prnt. HE institutions have Str-rdentSupport Offices which facilitate compliance, but the onus is on every staff member to get informecl and to conform. This is especiallyimportant given that the Act applies to people just enquiring about admission to a degree collrse as well as those studying on it. Lack of suitable aclapted facilities to aclmit a stuclent will no lonser be a valid reasonto deny them accessto a coufse. Speaking personally, having worked with a range of A-level biology students with visual imi-rairments, I think we tend to greatly unclerestimate their practical abilities ancl a well planned ltrb bench can allow even stuclents with no sight to do basic microbiology safely.See SchoolZone (p. ),/+7) for dettrils of a recentschool visit to my lab to do some cloning. Working in a genetics department as I do, it is only Iogical that str-rdentswith inl-rerited conditions may be interested in stuclying for a degree here. Students with disabilities represent a substantial, virtually untapped pool of high quality intellects that can populate and enrich our classesand tutorials with their valr,rableinsigl-rts given a small amolrnt of acljust- ment by the receiving institution. \i7e will be lr,rckyto havethem.

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'; ;;:;t; ;1 t TheBiochemrcal Societv The Genetics Societv ffiffi#ffi BritishSocietyfor Cell Biology and British Societyfor TheAG M of theSociety will Recentrecioients of awardsare: DevelopmentalBiology to hosta receptionin honour of be heldon ftresday 17 Dr PabloZunino, Institutode InvestigacionesBiologicas Sir Paul Nutse andDrTim Hunt, winnerswith Leland September at the Society Clemente,Uruguay - upto S5,4OO to studygeneration Harlwellofthe 2OO1 Nobel Prize in Physiologyor Medicine and meetingat Loughborough characterizationof P. mirabilisisogenicf imbrial mutants attheHouses of Parliamenton 8 October, University.Agenda papers, andsequencing of theUCA fimbrial operon rncludingreports from Officersand Group Dr Lioubov Vinogradova, All-Russia Research Areas of r€sponsibility for Elected Gouncil Conveners,the accounts of Institutefor Fertilization,Moscow, Russia- up to S5,700 Members theSocietyfor200l and a tostudythe phylogeny and nitrogen-fixing ability of a As parlof itsstrategyfor improving the communication specialresolution to amend phe n otypi cal ly id e ntif i ed Agro b acte ri u m radi ob acte r channelsfor ordinary members to Council,the f irstpairs of Article25 of theArticlesof (strain204) electedmembers acceoted their new remits. Professors Association,are in the Dr Keith Firman, Unrversityof Portsmouth- upto Hilary Lappin.Scottand Dave Kellywill have separateAnnual Report S 1,820to studylocal ization of the type I C restriction- oversightof mattersrelating to postgraduatemembers and bookletdistributed to all modification enzyme EcoR 1 24 1 inliposomes Dr Pauline Handley and Professor Golin Howard memberswith this issueof , Dr Ahmad Rasheed, Man galore U n ivers ity, Ind i a - up willconcern themselves with industrial liaison. They are MicrobiologyTaday, , hopingto developtheir ideas overthe summer and would to S6,000to studymicrobial prof iles and toxin production in - welcomeinput from members. Indianmonsooned malabar specialitycoffee Dr Evdokia Pentcheva, Un ive rs ity of EastAn g Ii a - upto S5,350to studychanges in the protein expression Delegates to the I U MS Genercl Assembly, ffiffiffikffiffiffi patternsafter infection of variouscelltypes wilh Chlamydia Paris 2OO2 strains Counci I conf irmed th e nominations of Professors Membersstill iust Sir David Hopwood andAlan Vivian, andDr Liz havetimetonbtitythe Dr Natalia Kalinina, MoscowState University, Russia- Sockettas itsdelegates tothe IUMS GeneralAssembly MembershipOffice at upto S6,137 tostudy biomolecular interactions between in Parisin July. They will take pad in the election procedures MarlborouohHouse of virus-codedproteins and host proteins by surface plasmon fortheappointment of newofficers. anvchano6s to their resonance adbress, ielephone/fax Dr Oleg Reva,National Academy of Sciencesof numbersor email details for Ukraine- upto S6,500 to studythe functional analysis of Proposed Life Sciences Federation inclusionin the new edition Bacillusgenesthat establish and sustain mutualistic of the SocietyisAddr ess Councilhas reaffirmed its position on the Federation, interactionswith plants and provide biocontrolactivity Book.tobe oublished later namelythatitwould co-operate in generic activities in this Pleasesend them Dr Robert Reed,University of Northumbriaat biologicalsciences,butwould retain its rights in allmatters vear. immediatelyto members@ Newcastle- upto g 1,900 to studythe effects of sunlight relatingto microbiology (see p. 1 34 forf urther details). - sgm.ac.uk onthe pathogenicityof Vibrioharveyi Thisscheme allows scientists to travelfromorto the IMM on-line at HighlMrc UK/Republic of lrelandto carryout a definedpiece of Councilwaspleased to hearthatagreement has been Seffiffiffiewwresearchin anyfield of microbiology,Applicants must be reachedfor the J ou rn al of Me d i cal M i c ro b i o I o gylo go of postdoctorallevel or above, The visits may be of upto WelcometoDrLuala'-.',' 3 monthsduration, The awards coverthe costs of return on-lineat HighWire, hopefully rn August, PfrnaveslnewStaff .' ' ', '," travel,a subsistenceallowance and a contributiontowards EditorontheJGV' , thecosts of consumablesinthe host laboratorv, Four cooies team,Luciaqained her O Alan Vivran,General Secretary ofthe completed application form and allsupIlementary qualification"satthe documentationmust be submitted to the SG M Grants rjniversiiies of Durham, Officefor consideration. The closing date forthe remaining WestofEngiand andfinally, , roundof applicationsin2002 is3ONovember, Leedswhere she studied for a PhD.This was followed bya postdocat Edinburgh il .-' ..;.:..,.., ..'.,',i'' :' University. Her researches - '. r.'uu"Joi,lr"J;;th" 1!i;5:'gg1,'\:ri:isllrir;,,:.i.;i;.,, .. .. l' , I"ittili molecularbjology of plan"t, tai! geneexpression, Membersare reminded thatfunding is again available forcompetition this year. The purpose of the Fund is to Andfarewell to DrTtacey assistmicrobiologists indeveloping countries and Eastern Duncombewno rs Europe.Members mayapplyforfunding to run trainrng relinquishingher post as coursesin developing countries appropriate tothe needs Public Affairs Ad m i nistrator of thosecou ntries, or for anyother small project to assistin to becomePress Officerat technologytransfer from Western Europe. The closing the InstituteforAnimerl datefor applicationsis 25 Octobet2OO2. Health,We wish her every successin this role, I ffim&ffiwwNWwwfuww WwNwwNwNwww ffiwm$wwwwwffiffiffiwwwwRw Www&Nwww SW I Retiredmembers are reminded thatthey may now apply $ffiffiKWW fora granttoattend one SGM conference each year, The awardcovers en-suite accommodation and the Societv ffiwmwwWw dinner,up to a maximumof $250.Applications for grants to Eligiblemicrobiology attendthe SG M meetingat Loughboroughare now invited. techniciansinuniversities, hospitals,research institutes,etc., may sample WwxffiwwffiwffiNwffiWwWwNmww anSGM meeting with expensesof upto S200 Highereducation institutions are invited to nominatefor beingmet bythe Society. anSG M Prizethe undergraduatestudent who performs Fulldetails were published bestin microbiology intheir penultimate BScyear. Each on p,83of the May2OO2 WwRwwW$-NNNp"* Ww.Nwffi ffiffiSN studentis awarded S50, a certificateand a f reeyear's issueof Microbiology undergraduatemembership. The prizes are intended to Today. Application s must fohn Grainger encourageexcellence in the study of microbiologyby bereceived bvthe-appropriate Grants Lecturetitle:Heeding the unseen:a necessarylife skill undergraduatesand to promotescholarship in, and Officeon the After awarenessof, microbiology in universities.Nomination formbefore the meeting. lf studying bacteriology formswere sent outto departments in May,butfurther youwish to attendthe atthe niversity copiesmay be downloaded from the SG M website.The Loughboroughmeeting, U of Birmingham, closingdate forthe receiptof applications bythe Grants apprynow. Johnmoved to Reading Officeis 3l August 2OO2. for hisPhD and was appointedto a lectureship there,eventually becoming Wwwm$$www Headof the Departmentof Swww$wwffiwffipwwMwww Microbiology,Involvement Wwwffi ffiRwmNwwKW* withschools began #smMffimmm ffiffiffiw''W innocentlyenough in 1964 TheFund aims to promotetalks on microbiological byproviding courses on topicsin departmental seminar programmes, Applications Theseenable practicalmicrobiology for areinvited from higher education institutions where undergraduatesto work teachers,He joined the microbiologyistaughtfor grants of upto S200towards the onmicrobiolog ical projects SGMTeaching Group traveland, if necessary,accommodation expenses of an duringthe summer vacation Committeein 1973 and became its represenlative on the invitedspeaker. Applications will be dealt with on a first beforethei r f inal year. They MicrobiologyinSchools Advisory Committee, In 1984, come,first served basis during the academic year, Written areintended to provide theSociety encouraged this work byfunding a projectat submissionsshould be sentto the Grants Off ice for undergraduateswith Readingto whichDr PaulWymer was appointed, This then consideration. experienceof research enabledJohn and Paulto secure DTI f undingto found andto encouragethem the NationalCentre for BiotechnologyEducation in i 98b, to considera careerin a Subsequentinternational developments incl uded the laboratorv-basedscience. EuropeanInitiative for BiotechnologyEducation in 19g j WwWwwRffiWwWwwwM WwwN Supportii providedatthe ofwhich John is afounder member,Althouoh retired Memberswho are permanently resident in adeveloping rateof S 150 oerweek for a f romthe universityand as Directorof NCBE,his work countryare reminded that they may apply for funding to maximumoeriod of 8 forschools continues, principally throug h SGM and acquirefor their libraries books, or possiblyjournals, relating weeks.Upto S400 may asChairman of MISAC, tomicrobiology. These annual awards are available as a alsobe awarded towards resultof a generousdonation f rom Professor T. Watanabe thecost of consumabres, ofJapan. The closing date for applicationsto theGrants Studentsare reouired ro Officeis 4 October 2OO2. submita briefreporl of their researchon the comoletion WwRMNwwmWww'Rqrewx- ofthestudentshio, W$wNWMRMw.$:wmww ffiSwwwRNww Thisyear 54 applications werereceived (one more Al Brown $swwffiwwmffiffiWWwmwwNS thanin 2001 ) and studentships were offered Lecturetitle: Dissectionof virulenceattributes in the - PWS&wwwffiw to 4 1 applicants,Alist of pathogen,Candida albicans a Gordianknot Grantsare availableto members for proiectsintended to awardeesis available from A profileof Al Brownwas published in the November2OO j leadto an improvement in the teaching 6f anyaspect of theSG M GrantsOffice, issueof Microbiology Today (p. 195). microbiologyrelevant to educationin the UK, This might Councilhas set aside a includethe development (e.g, ofteaching materials videos, furthersum to fundvacation slides,posters, CAL packages) or novelpractical exercises, studentshipsnext year, Full Fundingis alsoavailable for small projects to promote the detailsof the scheme will be publicunderstanding of microbiology, suchas workshops, announcedin the next issue talks,demonstrations, leaflets, activities atscience festivals. of Microbiology Todayand Applicationswill be considered ona firstcome, first served publishedon the SG M basis duringthe calendar y ear2002. website,

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Offercd WwsNwww Posters WwwwRNwxgw Meetings on 0fferedposters are welcome bLlt swYil$ssNs$*xN * N 0liviaCHAMPI0N (Dept of the web eachone should be associated with $N$s'$ N$*"S$sxmwg.* Infectious&Tropical Diseases, aGroup. General 0ffered Posters N$**ss$$m"g LondonSchool ofHygiene & Uo-to-daie information on TropicalMedicine) Construction willno longer be accepted. Titles il$sx$****"s$S*vr*ss$ futureSociety meetings is ofa gene-spetific conposite andabstractsshould beemailedto L,tsurghS*xr"*\L$$h availableon the website: theEvents Administrator, Mrs CanWlobacterjejuniD lrlA www.sgm,ac.uk $$*SSS*pt*sr-tN*r' JosianeDunn, atSGM HQ. The sss"t nicroarray subjectcontent should be relevant N DouglasWEST (Centre for O Main Symposium On.line tothe remit ofthe Group (see VeterinaryScience, University of 5taphylococcus booking websitefordetails); it does not have '16-'17 Cambridge)Characterization ofa torelate tothe topic ofthe Group September LhnAallelic replacenent mutant On-linebooking forms are 0rganizers:S,Foster,C. Gemmell, M Symposiumtakingplace atthe ofStrep[ococcus equisubsp equi nowavailable on the SG D.Hodgson H.Jenkinson& website. particularmeeting. Abstracts are N NatalieSIMPS0N (Dept - S,Patrick requiredina standard format see ofBiochemistry, University of Meetings websitefordetails orcontactthe 0ambridge)Regulation of organization EventsAdministrator, O Programme carbap enen pro d ucti on i n Booklet Erwiniasp, TheSGM meetings giving O Promega Prize N AndrewMACD0NALD (School program mes are organized Abooklet fulldetails ofthe programnte Final ofBiochemistry andMolecular bythecommittees of the Regional andabooking form is specialinterest groups, co- enclosedwiththis issue of 1iSeptember Biology,University ofLeeds) gy ges Functi on al conse quences of ordinated by the Scientific Meetings Mic ro bi o Io Io d ay. Any chan Promegasponsors thiscompetition website. interactionsbetween HCV NSSA Meeti n gs Officer, Professor willbe no$ed onthe SGM toencourage excellence in Proposalsarewelcome forone- proteinand Srcfanily kinnes HowardJenkinson. dayregional meetings. Thesewill scientificcommunication byyoung Suggestionsfor topics for usuallybefor postgraduates and O Ghange of dates scienti$sGroup Committees have S DavidL W00DHALL(Deptof futuresymposia are always firstpo$docs, witha keynote nowjudgedrecentoral orposter Medicine,University ofCambridge) 162for Pleasenote that the dates have welcome,See o. speakerandoffered papers or presentationsbymembers who are lhe h u nan cyton egal wi ru s contactdetails of Group changedfromthose previously workshopsessions, Theobjective postgradsorfirst po$docs The 72kDa najor imnediate early Conveners, advertisedforthe following pro[eininleracts physically and isto provide ausefulforum, symposia: finalistsfrom each Group orBranch Administrationof meetings particularlyforyounger goforward tocompete forPromega functionallywitha constituent of iscarried out by Mrs Josiane microbiologi$s,outsideSG M S Bacterialinteractions Prizesata special session ofshort NDI0 bodies, hDaxx Dunnat SG M,Marlborough matrix 0rdinaryMeetings. Funding is withextracel lular oralpresentations ontheir research. House,Basingstoke Road, upto two of these components Ihereare two prizes o{1200 to be SpencersWood,Reading availabletohold O Social Events year. Cells&Cell Surfaces Group wonand in 2003 the winners will go RG71AG (Tel.01 18 988 regionalmeetings each Pleasesubmit proposals tothe onto compete forthe title of Young Monday16September 1805; Fax01 1 8 988 5656; N]W1B Septenber WelconeRercption emailmeetings@sgm. ScientificMeetings 0fficer, , 0rganizers:RodMcNab (rmcnab@ LifeScientist ofthe Year againsl Tuesday17September ac.uk), HowardJenkinson, eastman,uclac.uk)& Anthony finalistsfrom other learned Smith(prsaws@ bathac.uk) societies.Thecontestants are: SocietyDinner WExtremophilesand NStefanieGEHRIG (Dept Wednesday1BSeptember ofPlant Sciences University of PubQuiz - entrance feefor charity astrobiology-atthe - Promega limitsoflife lxford) Lo cal izati on of th e p rote in prinsfor the winning tean !! producing Prize EnvironmentalMicrobiology duster anacetylated Thursday19September celIulose polyne r in the plant- Fveningreception [onark Areyou Group coloniilngbacteriun thelaunch ofthe fukaryotic amember ofthe SGM? N0W19-20 September Pn udo no n as fluo resce ns MicrobiologyGroup. apostgraduate orfirstpo$doc lateDavid Wynn- 0rganizers:the (Division inyour firsttwo years? Williamst Andrew Ball N DavidTURNER of thinkingofpresenting an ([email protected])[/icrobiologyandInfectious O Microscene offeredpaper orpo$er atan Diseases,University Hospital Noticeboard SGMmeeting? Nottingham)AspA,a nwel, conserved, in mu no ge nic and Atthemeeting aboard will Whynot enterforthe Promega Prize beset up with notices ofjobs, Competition?Youcould win 9200 in suface- ex posed n eni ngococcal autotransp o rte r pr ote in po$graduatestudentshi ps, theSGM section ofthe competition postdoctoralfelIowships, c0ttrses, andgo on to compete fora further S MichelleBARR(School conferencesetcContributions ae 12,000inthe Young LifeScientist ofAnimaland Microbial welcomeand may either be brought ofthe Year euent, Contact the SciencesUniversity ofReading) tothemeeting orsentto Janet g Meetings0ffice orsse website [nviro n n entallyi ndu ce d enes Hurstat SGM HQ beforehand. fordetails. ofrhinbia

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Other events J PIETERS(Basel Switzerland) iii;iFood fermentation O Regional Mol ec uI ar me chan isn s r nvolve d biology Bioinformatics p :..r-:! in hagocytosi s'le sso ns fro m i!f; *i!:Pj it,,- !i:::4, Fermentation&Bioprocessing/ Workshops2OO2 the i ntrac e|| u lar p ath og e n Food& BeveragesGroups with TheSociety issponsoring Mycobacteriunspp ScottishMicrobiological Society regionalBioinformatics Workshops -i (Berkeley, I, --'l r::.,.,.,,,,,1ili .:,t::i.li it.t.,-i RS STEPHENS USA) 0rganizers:J Rattray, M.Collins & throughouttheUK in 2002, Chlanydiadirecr'ed nodulation of O Main Symposium GHobbs O Main Symposium Theworkshops aimto give eukaryotichost cell functions Microbial subvercion rrliiEndothelial cell- Exploiting genomes: microbiologistswhohave aworking of host cells C IVI0NIECUCC0(Padova ltaly) pathogeninteractions basesto megabases knowledgeofcomputational Ce|| u Iar an d i nfl an nato ry ac[iviti es seqtlenceanalysis afirm grounding 0rganizedbyH F, Jenkinson, MicrobialInfection Groun in5oyearc ofvirulenrcfactorsof Hpylori inthe use of the late$ genome D.GE.Smith, C,D. 0'Connor & Othersymposia include: 0rganizers:PLangford &P Oy$on analysissoftware (Artemis and ACT) A,R.[4Coates PSANS0NETTI (ParisFrance) Microbialsensing and signalling/ ,iil;i,Molecu lar developedatthe Wellcome Tru$ Ihe p ro infl an nato ry resp onse aspects Analysisofbiological data/ 7April SangerInstitute Pathogen (Shisela) of anaerobes Molecularbiology: detection and [4J HU[4PHRIES(Manche$er) SequencingUnit.Artemis isa BR0IZI\/AN (Chicaso Physiology,Biochemistry & monrtoringinthe environment/ Curren[perspectives ofthe integrin USA) powerfulannotation tooland DNA Herpessinplex virus and apoptosis MolecularGenetics Group Po$-genomicsappliedto fieldand their relationship to viewerthat allows the user to analyse withSociety forAnaerobe processes:advances ineukaryotic cellularmicrobiology A ZYCHLINSKY(Berlin Germany) sequencedata generated in-house Microbiology microbiology/ProductionofD NA Toll' Ii ke rec epto r-tox in i n[e racli ons aswell as being able to upload and GFRANKEL (lmperial College andprotein/Genome-based inShigella 0rganizelN,Minton re-analysedatataken from EMBL or London)Pairprotein interactions detection/Geneexpression n andstructural analysis of rilirVaccines Genbank.ACTallows direct and (Symposium1) vivolDNA1 952-2003 : from ente ropathoge nic [, co Ii vrru Ie nc e O Other symposia interactive,comparisons ofmultiple structuretofunction genomes/sequences deterninants and workshops VirusGroup Formore informationabout these analysis (Bo$on, 0rganizer:[4Skinner R.ISBERG USA) ::l::TyPelV secretion toolssee http://www, sanger. Settingupa nestand naintaining it; systems ii$Viruses and cancer ac,ul

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'r;':r:;'r: ':,:r'::iri r:::i:;i:i: SchoolsMembership Visit by RNIB New Gollege sixth costsonlySlOayear, formers to the Institute of Genetics at Forthis,a named Nottinsham University teacherrepresentative ThreeA-level Biology students from the RoyalNational willreceive Instrtutefor the BlindNew College,Worcester, and their MicrobiologyToday teacherMr NormanBrown visited Dr LizSockett's lab for eachquarter, advance a dayto experienceat firsthand some practical genetic engineeringtechniques, including PCR amplification, notificationand copies plasmid-basedcloning and bacterial transformation that of newmicrobiology arepart of the AS/A2 Biologyspecifications. teachingresources, Thethree students were Emily, who is interestedin phys- feesfor anddiscounted iotherapyor a Biologydegree after her A-levels, and has attendanceon SGM partialsight and no colourvision, John, who hassome trainingcourses and sightin oneeye, and Sarah, who hasno sightat alland workshops,Appl ication whoreads Braille, unlike the other two who use large print. formsare available at Duringthe visit the studentsmet Helen Nankervis, who is www.sgm.ac.uk currentlydesigning SG M practicalsfor usein schools, and Karen and Matt,who are both researcherswith Liz. Duringthe daywe recordedwhat was beingsaid on a Website: Togetherwe explarnedPCR and DNA sequencingand smalldictaphone and Sarah took the tapes home with her, wwwmicrobiology revisedwhat the studentsknew about bacterial trans- As she said later,'the descriptionson the tape are really online,org.uk formation,plasmids and reportergenes. We let them good for revision,especially the detailsof how eachof the Enquiries: investigatelab equipment like PCR machines and micro- individualprotocols are carriedoul. The studentsand the pipettes,then got them to setup a PCRamplification for a [email protected],uk researchersreally enjoyed the interaction,The students specificgene and to transformcompetent E. coliwitha commentedIhaI'doing the actualpracticalwork makes it recombinantplasmid, and to makeand pourselective much easier to understandand the visit let us piece Ovgrto !ou... ampicillin,/X-Gal/IPTGLB plates to screentheir trans- together all the different parts of the cloning process tnto formants.We were quickly impressed by their knowledge, the sequencethat we are taughtat school Contributionsare manualdexterity and enthusiasm, Even Sarah was fully Fromthe lab sidewe did giveup a dayof the Easter welcomefrom teachers ableto pipettemicrolitre volumes in andout of Eppendorf vacationwhen we'd normally be doingresearch, but we who haveinteresting tubesand to pourand inoculate her plates after a single gaineda massiveamount from the infectiousenthusiasm microbiology material to run-thoughdemonstration. Indeed, when we counted of ourvisitors and were humbled by their intellects and the transformantsand sent the resultsto the school,her share,such as novel manualskills. By the end of the day eachof us could transformationefficiency was the best! investigations, usef ul imaginehow with only limited adaptations, we couldwork tipsor goodsources of Whilewe waitedfor ourtransformants to be readywe as undergraduateproject students or evenresearch col- information.Acopy of gavethe studentsa tourof ourlab, including our bacterial leagues.All that was needed was a wellset out labbench thepost-16 resource trackerwhich tests the motilityof bacteriafrom videos anda clearset of instructions.This is definitelya good of them swimming.The largevideo-screen images of thingto reportas the newSpecial Needs and Disabilities Practical Ferm e ntatio n the bacteriawere visibl'e to John and Emilyafter a few EducationAct startsto widen participationin higher (worthS15)willbe minutesacclimatizing to the lightingof the room,For educationto morefolk with physical impairments (see my senttoany school Sarahwe traced,with cardboard cut-outs,the journey of a articleon p. 140). whosesubmission is singlecell across the screento givean ideaof the speed. Fromthe school side it wasa successtoo. Mr Brown,their We also had an animateddiscussion about science published,The editors teacher,emailed us the nextday. 'What a brilliantday we and careersover lunch and laterwe visitedthe DNA oI MicrobiologyToday had on Friday, The students asked questions almost sequencingservice where Ingrid explained her role and reservethe rightto edit all the way home! Please thank everybodyfor all the time openedup a sequencerfor the student5 fs inrtactinate anymaterial, and effort that they put in, it was much appreciated,' Subsequently,we sentthem theirdata so they could calculatetherr transformation efficiencies (scanning photosof the colonieson Petriplates on to tactilepaper at our StudentSupport office for Sarah).Since then we'vehad emails from Mr Brownstill reporting on their enthusiasmfor molecularmicrobiology (and the odd TOPRIGHT: 'gigabug'joke as above!) Sarah,who is blind investigates a PCRmachine before helping to set We wishthem well with their Biology exams and their upan amplification futurecareers. O Dr Liz Sockeftis SGM Education Officer. She r.s RIGHT: based in the Genetics Division, School of Clinical whois partially Sixthformer John a n d Lab o rato Scie n ces, Oueen's M e d i ca I Schoo l, sightedgets used tosmall-scale ry University of Nottingham, Nottingham NG7 2UH, UK. pipettingwatched byclassmate Tel.01 159 194496; Fax 01 159 709906 Emily e m a i I Liz.Sockett @nott i ng h a m.a c. uk PHOTOSLIZSOCKETT

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Ajobirr,.. m$nifu,ffiffiffiwumm ffi ffiffiffi ffiffiffi mffi lf you haveany Gradline Editor ,,, {i,iDoyouthinkyou've TraceyDuncombe w. got what ittakes? storiesor news talks to Emma Sheppard 'l hooeso, While I wasat forpublication in about her workas a EmmaSheppard universityI tried to get lots or ifyou medicaleditor and her Gradline, 22 of relevantexoerience to aspi ration s of beco mi ng wouldlike to seeanv set me aboveother a science journalist. topicsfeatured, candidates.In mvfirst MedicalEditor,SciencePress Ltd, pleasecontact yearljoined my itudent t;t, What does editing London newspaper,IheWarwick mtoday@sgm. involve? {" Boar,andwrote weekly Lrl'ltiril.rillililli:ilitiliH+iti ac.uk forthe Newssection, I As a MedicalEditor EditorialAssistant, Science Press at SciencePress I am enjoyedwriting in this involvedin almosteverv styleas it was informative, stageof the publishing lll,*,,0,,'o-', likescientific writing, and process,We publish BScMicrobiology andVirolc it was fun to interview ,sy peopleand create a slant booksaimed at G Psto UniversityofWarwick informthem of the latest $ on eachstory,lentered druoson the market, Ihe DailyTelegraph Ourclients are the pharmaceuticalcompanies who Young Science Writerof the YearAwards 2000 manufacturethe drugs. andwas very surprised to reachthe finalswith a piece on the roleof Campylobacterinfoodpoisoning, It'sa variedjob, which involves taking a bookf rom the manuscriptstage ihrough to the finalprinted I havebeen interested in writing scientific version,Some days I editthe text(for sense as wellas materialsince doing my A-levels and was very content)and otherdays I edit on-screen,proofread or oleasedto discoverthat a ScienceCommunication checkadvances from the printers.l've been trained coursewas one of the availablemodules in mydegree. howto editproperly according to our housestyle, Thecourse comprised a seriesof workshopsessions usingthe specialsymbols editors use to denote runby an ex-New Scientistlournalist.Our group whatshould happen to the text,Once I've edited a carriedout role-playsof interviewsand came up manuscriptIthen haveto makechanges to the Word withideas for museumexhibits and NationalScience documentand mark the textand figures to betypeset. Week.lt allculminated in the productionof a small Thisis when the text is laidout on pagesas it would oortfolioof workthat demonstrated how I could appearin the f inalcopy, After checking once more for communicatescience in differentwavs. The errorsthe bookthen goes to the client.Sometimes courseworkvaried from interviewinga memberof they mayquery parts of the text and I haveto liaisewith staffabout research and writing an articleon itto the authortoensure thatthe final book satisfies the planninga radioshow and designing a leafletto autholthe clientand Science Press, which can take informthe generalpublic about stem cell research, sometimelOnce we get permissionto go aheadthe I put a lot of hardwork into my portfolioas I was f ilesare sent to the printgr.My f inaltask isto checkthe determinedto do well.lwasoverthe moon when I printerproofs to ensurethat the colouris correct and got the result,I got a f irstclass mark, lt was the f ileshave not corrupted. confirmationthat I wasactually good at doing somethinglenjoyed so much. It isvery rewarding when I receivethe bookadvances asthe wholeprocess takes many months f romreceipt Toget a job inthe mediayou musthave a lotof of the manuscriptto publication.As wellas working on exoerienceand useful contacts, I decidedto make my own projectsI proofreadother people'swork, the mostof my universityholidays by gettingsome includingSpanish and Portuguese texts, which is very relevantexperience. As wellas shadowingsomeone interestingas I speakneither language. at NewScientist,larrangedto shadowan AngliaTV I'vebeen very lucky in havingsuch a goodfirst job, lt newsoresenter to seewhat television work was like, hasprovided me with afirm groundingin the basicsof Afterstanding outside a courthousefor mostof the publishingand l've learnt many new skills that will help daywithout getting an interviewI decidedthat perhaps me to developmy careerl televisionwas notthe careerfor melI insteadchose to followa careerin printand I'm now trying hard to qJt Where do you see your career-Teveloping? expandmy portfolioand get morework publishedl 'My dreamjob hasalways been to writefor New 'ffi Where do you go from here? Scientistora similarpublication, I emailed lVew 'l'm Scientista6outgetting work experience and ended up tryingto createmore opportunities for myself shadowingan OpinionEditorforthe day. I learntmany by approachingdifferent com panies for f reelance usefu I tech n iques, incl ud i ng the standardnotation work.I haverecently passed a test for a websitethat usedby sub-editors and how to edita pieceof workto produceshealth news so hopefullyl'll be carryingout fit a page,skills that I now usedaily, I was shown the workforthemin the nearfuture,l'malso writing a integratednature of journalism and the linksbetween chapterin a biologytextbook,which I'm looking eachdepartment, which are needed to producethe forwardto seeingpublished, Maybe my nextjob will perfectpublication, He convincedme that publishing havemore of a writingrole, bui I'mpretty happy with wasa goodway to get intowritingJ what l'veachieved so fari

n/AUG02 .* .:: ::... .. N- ,."o*"o.* e ,oi -*."* : i1 -. i:'.,- :. ' MicrobiologyToday \]*$\\*.FSd \5 .;". {,.;: :'.:: -:....".:.:.':. 'ti: . : : :: .... EditorMerielJones g$'*gt ij,.:' ';ni :':.:i'.. :..: ..' . i" . r ..: :. .. ::..1q . si,:*.r"ir$.: ;q;ia .;.. : takesa lookat some Softdrinks are a hostile Thereis a bigmarkettor papersin current environmentformost monosodium glutamate, the issuesof the microbesbecause they are ubiqu itous taste en hancer Society'sjournals soacid. However, a select listedas MSG in many whichhighlight new feware able to livein this preparedand oriental foods. andexciting acidic,sugary environment, Worldwideproduction andtheir growth spoils the exceeded1 milliontonnes developmentsin f lavour and appearance of ini996.Muchof itcomes microbiological thedrink. Researchers at frombacteriaof the genus research, \s^NssxNs$*..*."NwsN ss*- sNNxssN UnileverR&D, working with Corynebacteriumlhal colleaguesat the National secretelarge amounts of Microbiologistswould like know to howto tell when Collectronof Yeast Cultures, glutamicacid as they grow bacteriaare really dead, and when they are alive but havejustaddedCandida invast ind ustrial fermenters. unwillingto grow. ifthe microbes just Obviously, have been dave n po rti i to thisexcl usive Oneproblem is that the cookedin an autoclave, not theyare shammingdeath, but band,named afterthe late growingbugs generate manysituationsare less clear-cut. Researchers can often ProfessorBob Davenoort. so muchheatthatthey grains seebacteria on of soil,or samples of animaltissues, whosework with spoilage dieunless complicated butcannotgrowthesame ones on culture media. In asimilar yeastsin softdrinks is coolingsystems keep the way,tools from molecular biology have revealed the legendary.The trail started temperaturedown. possible existenceof vast hordes of microbesin every withacommon wasp lying Onesolution would be environment,few of which will grow in the laboratory. deadnextto afew drops of to usebacteria that enjoy syrupfrom the sampling tap Apartfromphilosophical interest, there are very highertemperatures, practicalreasons of anexternal sugar syrup for wantingto understandwhat is Japaneseresearchers happeningin these situations. lf tankat a Eurooeansoft apparentlyviablebut fromAjinomoto, the world's 'non-cultu rable' pathogen ic bacteria can ever be ind drinksfactory, Although the ucedto largestproducer of MSG, growagain, they could be medically important, ratherthan a yeastisolated from the wasp andfrom the University of scientificoddity,Tuberculosis isone of the lookedperfectly ordinary, diseaseswhere Techn ol ogy, Toyo h as h r, thereis an argumentaboutwhether, and hoW biochemicalandDNA bacterialcells havenow discovered a canpersist in the bodyforyears before becoming active testsshowed that it was newspecies with exactly andcausing disease. sufficiently different f rom the this characteristic, In trials, otherB00known types of Co ry n e b acte ri u m effi c i e n s Researchersatthe Bakh Institute of Biochemistryin yeasttobe a newspecies. Moscow and the Un iversity of Wales,Aberystwyth, have pumpedout over 1 '0 g beencollaboratin g for several years to study'non-culturable' Itsmost notable glutamicacidl-1 while 'C, bacteria.They have studied.both an avirulent strain of characteristicwas that ii was growingvigorously at 45 Mycobacteriumtuberculose the bacteriumthat causesTB, moreresistantto acetic acid Thebacteria were orig inal ly andits non-pathogenic relative Rhodococcus rhodochrous. thanalmost all other spoilage isolatedfrom soil and an Theyhave discovered thatseveraldays after R. rhodochrous yeastsand could grow even onionbulb, and described hasused up allthe food in the growth medium, there is a at pH 1'4.Anotherinteresting inaJapanese patent discrepancyofupto 10,000-fold between the numberof featurewas that C. application,They could now bacteriathatare visible and the numberthat can be induced dave n po rti i and otherclosely bea pieceof hotintellectual to growby changing the growth medium, However, adding a relatedyeasts are associated properry. withbees and wasos. Most smallamount of liquidfrom growing cultures decreased Fudou,R.,Jojoba, Y., Seta, A., of themhave thesedifferences. The reason turns outto be minute beenisolated Yamada, K., Kimura,I., amountsofasmallprotein called Rpf, released bythe fromthese insects and may Nakamatsu, T., Hiraishi, A. growingbacteriaThe same sortof phenomenon happened becarried bythem to infect, & Yamanaka, S. (2002). withM. tuberculosis,where even 5 monthsafterthe cells andso spoil, sugaryfoods. C oryne bacter i am ffi cienssp. nov., a hadapparently ceased growth, adding Rpf, or liquidfrom a So notonly is there ahazard glutamic-acid-producing growingculture, triggered their revival, lf M.tuberculosis frombeing stung bywasps speciesfrom soil andvegetables. cellscan really enter a stateof deepdormancy, this may ata picnic,butthey may be IntJ SystEuol Microbiol 52, rr27-tI3t. explainwhyTB can suddenly re-appearyears afterthe carryingyeasts that could infectionwas ostensiblycured. Finding ways to blockthis spoilthesoft drinks. resuscitationmay eventually offer new treatments for TOP: Stratford,M., Bond, CJ., thisdisease. S.A.,Roberts, Scanningelectron micrograph of James, I.N.& Steels, H. (20O2). Candida asmall cluster ofcells of Candida Shleeva, M.O .,Bagramyan, K., Telkov, M.V., Mukamolova, dauenpmtii sp. nov., a potential davenportiiIar,lpn. G.V., Young, M., Kell, D.B. & Kaprelyants, A.S. (2002). 'non-culturable' soft-drinks spoilage yeast isolated COURTESYMARKKIRKLAND AND Formation and resuscitation of cells ofR hod.ococcus from a wasp. 1ntJ Sys t Euol MALCOLMSTRATFORD, UNILEVER R&D rhodocbrousand Mymbacteriun tubacu losis in prolonged stationary Minobiol 52, 1369-L3l t. COLWORTH phase.Minobiokg I48, 1 5 8 1-1 5 9 1 .

N\NSNS\NNNSN"S{\N*TODAYVOL29/AUGO2Ifl RIGHTT i::.;ii$i!$i ji;*,,ri'' iiiilii;; ii;g*:'r"* * *;;sri *X gn gil**p*'X S $' [ {,ii SymptomsofJapanese hydrangeaphyllody phytoplasma ,1,$tt,t$'ri$:rfrr"s{ i:tj;:is$,*ru i$;$.l$'$ :is${$p$"w:-$:r*.asi*$ (P p j hytoI asn a apo n i cun) i nfection Phytoplasmasare very small, wal l-less bacteria that I ive ona Japanese hortensia plant exclusivelywithinthe phloem of plants.Theyhave among (Hyd ran g ea n acr op hy || a f. nacrophylla),Adiseased flower thesmallest numbers of genes of any living organisms, showingtypical phyllody symptoms beingable to relyon their unwitting hosts for manymaterials. (developmentofthe floral parts Themain reason for being interested in phytoplasmas isthat intoleafy structures) isshown theirparasitic lifestyle causes disease, To date,over 600 (bottom)below anormalflower diseasesin at least 3OO plant species have been ascrtbed (top)Diseased plants also show to phytoplasmas,but because they cannot easily be virescence(thedevelopment of separatedfrom their hosts they areverydifficultto study, green flowersand loss of normal Theonlywayto maintain a phytoplasmaforresearch is in flowercolour), proliferation of infectedplants in a greenhouse,Since the phytoplasma is auxilary shoots resulting ina witchesbroom appearance transmittedin the saliva of sap-suckinginsects, the plants necrosisinthe phloem dieback of haveto bewithin insect-proof containment, and a suitable branchesandeventual decline insecihas to beavailable to propagatethe phytoplasma PHOTOCOURTESY DRSHIGETOU to newolants. NA[/BA r:r:;: Researchersatthe Universityof Tokyohave been $t $!ugr:i'_ii'i,',::r::, li-ij!*:.g qip'5$ $ ",* $F$$'$ gXeX$ WXR$ WXg studyingthe phytoplasma responsible for onion yellows '$,$'$l$:l !PPOSITEPAGE: ::i::$'il::l'ii.'i:!{i:ili$i; iii"\{$*$Si$ $i-$:*$$i $S$S'$W W (OY-W). A reminderofthe FMD crisis in the disease Thisproduces a widevariety of symptoms $x,,ll$qii::i:.i :.'!:.i:,1,:i lt,;t ::r; r'ttt+**:"S$$ ;ffii$i'S.fi:$ Xg*g'C* $WWBffiffi UKin the stlmmer of2001 inits plant host, including excessive greening of the flowers, (FM PHOTOIANATHERION andflowers with leaf-like petals and sepals,yellowing ofthe Theoutbreak of foot-and-mouth disease D)in the leaves,stunting, and excessive proliferation of shoots,They UK in2001 didnot end without a massiveeffod, involving maintainedthe phytoplasma on garland chrysanthemums restrictionson farming and access to thecountryside for andused a leafhoppertotransmititfrom plantto plant. Ai months,as well as the slaughter of milfionsof animals,The onepointavariantof the phytoplasma(OY-M) arose that progressof anoutbreakof FMD in Greece in 1994was producedmuch milder symptoms than the original strain. verydifferent. Although it started with a lotof illnessin sheep TheSGMpublishes Theresearchers im med iately wondered what change f locks,ihe numberof casesdeclined sharply after a month twomonthlyjournals, hadoccurred in the OY-M line, andthe disease finally appeared to dieout of itsown Mictobiologyand accord,This sort of behaviourhas been recorded before Theyknew that the genes for pathogenicityinbacteria are toumalof Genenl inoutbreaks among small flocks. lf it reallyoccurs, it could f requentlynot carried on their chromosome, bui instead on Wrolagy. shedsome light on exactly why FM D isso virulent. smallexira pieces of DNA,called plasmids, They had already fhe Inbmational discoveredtwo classes of plasmidswithin OY-W the smaller Researchersat the Institute for Ani mal Health at Pirbri g ht, loumalolSystematic ofwhich was missing from OY-M,TheJapanesegroup have UK, col laborati ng with the Centre for Tropical Veteri nary andEvolutionary nowreported their most recentfindings in Microbiology, Medicineatthe University of Edinburgh,inthe U K, set up an Microbiologty@9iEIII) whichgive further insight into the evolution of thesetwo experimenttoseewhetherthe Greekstrain of FMDVreally ispublished bimonthly phytoplasmalines. They have found athird class, present in didbecome less infectious as it spread. They infected one onbehalf of the IUMS in bothOY-W and OY-M, which looks as if it hasarisen by smallgroupof sheep with the virus and then letthem meet conjunctionwith the ICSP recombinationofthetwootherclasses and has lost withother sheep, in an arrangement designed to mimicthe Thethreejournalsare someof itsvirulence along the way, spreadof diseasebetween flocks in real life. The amount of virusin the blood of infectedanimals usually correlates well nowavailable online. For phytoplasmas,recombination Althoughthis is afirstfor withthe infectiousness ofthatanimal, and itturned outto furtherinformation visit the plasmidsis awell-known feature in bacteriathat between belowerin sheeothatwere infected lateron. journalwebsite:wunu, playsa malorevolutionary role by creating genetic diversity sgmioumals.org andprovides the potentialforrapid adaptation to new lf aninfectious agent is to maintainitself through an Membersmay environmental cond itions, Since phytoplasmas are so unbrokenchain of infections,it musi maintain the level of purchaseSGM journals dependenton their hosts, any mechanism for increasing infectiousnessof each newly infected individual, or itwill atconcessionary rates. their biologicaldiversity could be of great si gn if icance inevitablydie out, In this experiment,the peak amount of .l Seep, 17 orcontactthe for iheirpathogenicity, virusin new infections decreased by about 50 0/oover only MembershipOffice for 3 weeks,suggesting thatthis strain really could not Nishigawa, H., Oshima, K ., Kakizaw a,S., H.-y., Jung, maintainits transmission, which agreed with the records of details,Information on Kuboyama, T., Miyata, S.-i., Ugaki, M. & Namba, S. (2002). commercialsubscri otionsis Evidence of intermolecular recombination between itsbehavrour inGreece in i 994.How long it would really availablefrom the Journals extrachromosomal DNAs in phytoplasma: a trigger for the taketo disappearin real life would depend on a hostof SalesOffice, biological diversity of phytoplasma? Minob iology I48, 1389-1396. factors,butthe researchers now wantto f indout howthis straindiffers from others, to pinpointthegenes that controlits infectiousness and virulence.

Hughes, GJ., Mioulet, V., Haydon, R.T., Kitching, R.P., Donaldson, A.I. & Voolhouse, M.EJ. (2002). Serialpassage of foot-and-mouth diseasevirus in sheep revealsdeclining levels of viraemia over time.J G enVirol 83, 1901-1914. lEi:itrr*i!::t;i.is$*rilFir;{}*YTODAYVOL'p,/AUGO2 ffimpwam#wwmm# wmwm#ffiffs .*, WffiSffipqswm" w$w$ ffi ** $$wsx$.$;$sxis$jt$:*q:*$.Ss-sNqS %Wwpmxwm$w qp$eerewmm$wx6$-$$s*r Therecent U K FMD ofvirus in the airwas enough wasprobablythe large ffimtrfumffimse$eT*e-F* outbreakwas a heart- to leta sheepbreathe in an amountof the virus they rendingexample of infectiousdose in only 5 wereexposed to, In real life, Bacterialmeningitis is caused by Neisseriameningitidis howthis highly contagious minutes,and the other four thedisease would be whichcan be detected in the nose and throat of many virusdisease of livestock sheeprapidly became transmittedless quickly if normal,healthy people. The proportion of suchcarriers canresult in oersonal infected.These initially thesheep were scattered variesconsiderably, but can be over 40 0/0,However,only despairforpeople showedvery little sign of acrossfields or hillsides, but N.meningitidis,and one other member of itsgenus, are dependenton agriculture illnessbut excreted airborne couldtravelswiftly ifthey capableof causingdisease. Researchers would like to andrural businesses, as well virusmaximally within 48 werebrought together for knowwhy some people very occasionally become seriously asthe culling of millionsof hours.Bythe sixth day, all anyreason, such as ill,while most live all their lives with N. men ing itidis as a animalsto controlthe thesheep were obviously ill, shearing.The factthat harmlessinhabitant. infection,Thehighly butby that time, although sheepare most infectious Oneof the distinguishing features of the bacterium is its contagiousnature of FMD, theresearchers could beforethere are any obvious thickcoat of complexlipids and polysaccharides, called a andthe drastic measures detectvirusin the swabs, signsof illnessis very capsule.Thiscan protect itfrom the immune system during usedto eradicateit, were therewas none in the breath importantfor working out aninfection, and may have the more biologically important shownon thetelevision for ofthe sheep. Antibodies to strategiesto containFM D, roleof preventingthe bacterial cells from becoming dried up months,Sheep played a FMDVin their blood Theresearchers hopeto use inthe airsothatthey can spread from person to personin majorrole in the spread of indicatedthat the immune thedetailed results from this coughsand sneezes. The detailed structure of the capsule thedisease becausethe systemsof the sheep were experimenttodevelop letsresearchers assign each strain to oneof 13 groups. clinicalsignsoften are mild gettingthe infection under improvedcomputer models Virtuallyallinfections come from onlyfive of these groups, insheeo. This means that controlbythis time, This for predictingthe spread of althougheven then most people carrying these strains do thevirus can be transmitted matchedwith the thedisease,as wellas notfallill. Nevertheless, researchers are convinced that frominfected sheep to other decreasingamounts of live recommendingpractical understandingmore aboutthe capsule may helpthem animalsthrough their breath viruswithin the blood stepsto limitits spreao. understandwhy afew strains are pathogenicwhile or bycontact before anyone samplesorswabs. One Alexanderse n, 5., Zhang, 2., realizesthere is a disease monthafter the startof the mostarenot. Reid, S.M., Hutchings, G.H. oroblem, experiment, the researchers Researchersled by Ulrich Vogelatthe Universityof & Donaldson, A.L (2002). couldstill detect very low i nfectiousvirus Wrirzburgin Germany, collaborating with Martin Maiden Veterinaryscientists at the Quantitiesof levelsof vrrus in throat and viral RNA recovered from fromthe Universityof Oxfordin the UK, recentlytested Institutefor Animal Health samplesfromhalf of the sheep and cattle experimentally 8,000healthy schoolchildren and young adults from Bavaria atPirbright, UK, have now sheep,indicating that they i nfected wi th foot-and- mouth f N.m ni ng?dis J ust over 1O o/o car ried th e bacteriu m, reportedastudy into how or e werenow virus carriers. diseasevirus O UK2}OL.J Gen and 16 0/oof thesestrains lacked several of the genesthat readilytheviruscan be Virol 83,1915-1923 . arerequired to synthesizeacapsule. Synthesizing the spreadamong sheep, and Thereason thatthe sheep capsuleis quite complicated, The bacteria have to builda alsohow much airborne becameinfected so quickly virussheep actually excrete seriesofspecial lipidsand sugars,transportthem ontothe r surJaceof thecelland then join them together.A large asthe disease progresses. numberof genescontrol this biosynthesis. Theresearchers keot 10 Dorsetcrossbredewes in a Whenthe researchers examined exactlywhythese biosecurebuilding, and bacteriano longer made capsules, they discovered that infectedsix of them with theacapsulate strains fell into at leastfourdistinctgroups, thestrain of the virus that Genesforthe synthesis, lipid modification and transport causedtheUKeoidemic. ofthe capsular polysaccharide had been replaced by a Fromthen on,they shortlength of DNAthatdidnotencode anything.The examinedthe sheep for researchersobviously wondered where this had come from. signsof diseaseevery day, ( Theywere not entirely surprised when they worked out collectedsamples of blood, I thatit originatedin the specieslVer'sse ria lactamicaand andtook nasaland rectal tl t hadbeen transferred to N.meningitidisonseveral different I swabsto testforthe virus, I occasions.The species of Neisseriaarewell known to tl Theyalso col lected samples rl begenetically diverse, and to exchangegenes among of airfromthe room housing themselves,and with other species of bacteria. thesheep so they could Althoughthe biological role of the meningococcalcapsule measure whether there was isstill unclear, the fact that it is absent from particular groups virusin their breath, ofthe species suggests ihat these are less dependent on FMDVmultiplied rapidly in acapsuleforprotection during transmission than other thesheeo. and the infected groups,The reason forthis still awaits discovery. sheepshed virus into their Claus, H., Maiden, M.CJ., Maag, R., Frosch, M. & Vogel, U. breathand surroundings (20D2).Many carried meningococci lack thegenes required for only24hours afterthey capsulesynthesis and transp ort. MicrobiologyI48,l8l3-I8I9. wereinjected. The amount lnternational DevelopmentFund rcport

SGM helps lmprovingwater quality in theyshould stop me at microbiologistsin China anytime to askquestions. Luckily,the age rangeof developingcountries I GwynJones thestudents was from21 andEastern Europe to 40 andsome of the olderand more confident throughthis fund, Thiswas myfifth visitto China, specificallyto onestook the lead,I also usuallybysupporting HebeiProvince which surrounds Beijing, and where emohasizedthatthe I hadbeen involved in advisoryworkin the past,The trainingcourses wholecourse content was provincehas a populationof about55 millionand the andothersmall inthe textbooks that I had industrialcity of Shijiazhuangaccounts for about takenout withme, so technologytransfer 3 millionpeople, Pastvisits have been underthe therewas no needto projects.The closing ausoicesof the BritishExecutive Service Overseas take notes.They could, (BESO)or byspecialinvitation of the Chinese dateforthe current of coursecontact me bv Academyof Sciences,BESO is a registeredcharity emailtoask questions, roundof applications thatcollaborates with countries in Africa, South and I am happytoreportthat several have done so tothefundis25 Americaand Asiathat require specialist advice, usually srncemy return, October2OO2 f romretired experts. I have, at times,thought of this (seep. 142for processas VSO forthe wrinkliesbut, in so doing,I am Havingbroken down the barriersof formalteaching, surethat I am doinga greatdisservice to myfellow thingswentverywell,ltwas not long before astudent details), volunteers,Whilst pastvisits provided the opportunity said'Youdon't have to speakso slowly- we do to adviseon environmentalproblems on a day-by-day understandyou'.fhis,l suppose,was athrowbackto basis,there was littlechance to examinea single myteaching experiences in Argentina when I wastold 'fluid problemin depth, thateveryone was in English- andthey weren'tl Bythe seconddaythe students were quite happyto Thebulk of theexoertise in this arid zone is in stopme if I hadused aterm thatthey not agricultureand horticulture, and the organizationwith did understand.Once written on the board, whichI hadestablished the mostoroductive contact theytapped it intotheir hand-held translation devices wasthe Instituteof AgriculturalModernization. More and,after a briefstoppage, this resulted in a classgasp 'Ahh- recently,the Institutehas been charged with solving of that'swhat he'son about.Thereafter,this worked quite waterquality problems in the region,specificallythe wellandlfeltthatwe had established rapport. eutrophicationof the massiveDalangdian Reservoir some andthe grossfaecal pollution of the CityRiver, The The coursestarted with the basicsof freshwater earliervisits had shown that the transitionf rom soil to physicsand chemistry and then developed into how f reshwatermicrobiology was going to be a majorstep, microbesmediate the reactions,particularly under withlittle understanding of how lakes,reservoirs and conditionsof stratification, Clearly, the processesof riversfunction, particularly in relationto the scaleof anaerobicrespiration and the scaleon whichthey microbiallymediated redox reactions, occurrepresented totallv new information,We then progressedto sourcesoT pollution that, in part I was,therefore, delighted to hearthatmy application this of the world,is largelyfaecal, with industrialovertones to the SGM Internationalpevelopment Fund had been in the formof heavymetals. I decidedto concentrate accepted,Even more so, that Janet H u rst and her on the former,as there was not enoughtime colleaguesprovided me (atextremely short notice) to dealwith metaltoxicity, My equipment included witheducational materials, including excellent posters somesamplers for countingcoliform bacteria, Each student was given and copiesof MicrobiologyToday.ln addition, I took oneand asked io dipit inawater bodyof hisor her(the out severaltextbooks, and the grantcovered about majorityof studentswere female) choice, not S 1000 worthof membranefiltration eouioment, John Walkeron the Chinadesk of BESOwas delightedto be a co-soonsorand coveredmv -excellent U K travelcosts as wellas usingthe organization's contactsto obtaina visaat shortnotice and orovide insurance anddiolomatic cover, So,I waswell equipped and on myway. I was introducedto the students(the class size ranged from 40 to 100 dependingon dailycommitments) by the Principalof the University,and then left to get on withit. The first barrierto be brokendown was oneof formality,There was a greattendency to try to write downevery word I spokeand on no accountwas Ito be interrupted.This clearly was notgoing to work,as I wantedinteraction with the studentsand lwanted themto thinkabout what I saidand to ouestionme as soonas they did not understandanything. We managedto overcomethis on the firstday when I wroteon the boardthat myname was'Gwyn'and

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forgettingto testthe tap waterin the building,Bear in mindthat, even in the besthotels in Beijing,the tap wateris notf itfor humanconsumotion, You either drinkbottled water or boiledwater that is orovidedin yourroom oron anytrainjourneythatyou make,lf you haveany sense, you purchasesome of the excellent Chinesegreen teas to addto the boiledwater and this makesa refreshing drink, The only other options are Westernbeverages such as Cokeand Seven Up. Althoughthe Universitydid not haveappropriate incubationfacilities, prolonged incubation at a lower temperatureprovided results adequate enough to convincethe studentsof the shortfallin water quality. We thenexamined what constituted a sionificant differencein the results.Although wellv6rsed in computer-basedstatistical packages the students wereunaware of the limitationsimoosed when small samplesare taken and subjected to statisticsbased on the normaldistribution curve. We examinedthe use of non-parametricstatistics and how such tests may provemore powerful in detectingsignificant differenceswhen small numbers of samplesare taken. Luckily,the resultsof algalcounts on the membrane filters(almost always a Poissondistribution) proved the pointnicely, Thesebore the nameof the SGM to emphasize the ABOVF: contactand were much appreciated by all. ProfessorJones with two students I hadplanned to endeach day with a casestudy. I had outsidetheUniversity assumedthat the studentswou ld befairlv tired after 5 We werealso able to visitDalangdian reservoir and hoursof solidteaching in a foreignlanguage, so this useit as a casestudv closerto home. This water bodv TOPLEFT: wasa goodopportunityto get overthemessage that is large(17 Xnz)andis filled by canalized water Thecourse isannounced microbiologycombined with active management can f romthe YellowRiver (85 x 106 m3volume) over an resultin imorovement of theenvironment, The astonishinglyshort 3 weeksin winter, Forthose of BOTTOMLEFT: examplesthat reallyseemed to catchtheir imagination vouwho knowthe LakeDistrict, that iso reaterthan Samplingtnemassive Dalangdian werephosphorus stripping to reducecyanobacterial ihe totalvolume of Haweswatei,our lar!estreservoir. Reservoir blooms,the use of Bacillusthuringiensisto control Thereafter,water is drawndown to a depthof one insectpests such as the BlandfordFly and the useof metreand, as summerprogresses, blooms of the PHOTOSJG JONES anaerobicbacteriato cenerate base in waters subiect cyano bacterium Mi c rocysti s aer ug in osa deve I o p, to acidoollution, renderingthe waterunusable for anythingbut irrigation.The students quickly registered I mentionedabove that Ithought that the students thata slower ! fillingregime combined with treatment (possibly mightf indthe course a littletiring. I had not allowed by phytoremediation) was requ i red, However, events forthe excellentChinese hospitality during the week. haveovertaken any possible remedial measures, Eachlunch break we wentto a nearbvrestaurant and as plansare well underwav to transferwater f rom consumedfar more than my usual 'soup and a rolli the YangtzeRiver to the YellowRiver and to treble Whilstthis was delightf ul, if onlyfor the opportunityto the size of the reservoir,lamcurrently involved in discussions, talkinformally to the students(different groups were followingthe publicationof ajoint paperwith invitedeach day), we were a graduatestudent, on the possibilityof introducing allfairly soporif ic atthe the waterinto a wetlandbefore it entersthe enlarged endof suchlarge meals. reservoir,This would provide the opportunityfor The Un iversity, however, plant,/microbeinteractions in a reedbed system waswell prepared for to stripmuch of the excessiveload of phosphorus, suchan eventuality,and Hopefully, some of the f uture students will be lwas providedwith a ableto studythis process. bedroomfor an hour beforethe afternoon I hopethat the coursedemonstrated that microbes lecturesbegan, I haveto can be usedeffectivelyto improve water quality. The admitthat, on the first responsef romthe studentswas morethan day,l sleptvery well, encouraging,so I am verygratefulto the SGM forthe Thereafter,it was a good opportunity to takethis message to China. opportun ity to sharpenup I Professo r l. Gwynfryn I o n es wa s fo rm e rly the afternoon'slectu res. Director of the Institute of Freshwater Ecology Atthe endofthe courseI and the Freshwater Biological Association, gavea signedcertificate Windermere. He m ay be contacted at The Orch a rd, to eachstudent who had Oldfield Road, Windermere LA23 2BV UK. comoletedthe course, e m a i I gwyn f ryn @bti nte rn et. co m lnternational ResearchFellowship rcport

whichrequired typing were isolated from the NICU oatientsat Leeds, The epidemiologyof nosocomialC. parapsilosis infectionis complex and poorly defined and may involve colonizedpatients and hospital personnel, lt hasa uniqueability to adhereto plasticbiomedical devices andsurvives on environmentalsurfaces, Restriction fragmentlength polymorphism (RFLP) analysis with andwithout probes, randomly amplified DNA (RAPD) analysis,pulsed field gelelectrophoresis (PFGE) and otherPCR-based methods are usedto investigate outbreaksof candidiasis,These methods are primarily usedto identifyindividual strains and to detectpossible cross-infection,One of the mostversatileis southern- blothybridization with species-specific complex DNA probeswhich has been reportedto be particularly effectivewith C.albicans.Therefore, it was decidedto %, SGM International TypingGandida parapsilasisstrains Research Fellowshipsenable fromnetlnates scientiststo travelto I RomaBatra orfromtheUKand lrelandto carryout a Beingan enterprisingmycologist, myjoy knew no definedpiece of boundswhen lwas qivenan opporlunitybythe SGM researchinanyfield to work at a worldfairous myiologycentre - the $i.," ;; of microbiology. MycologyReference Centre atthe Universityof Leeds, Visitsmay last up to I arrivedat ManchesterAirporton 30 April2001 , full of enthusiasmto undertakethe researchoroiect. Then I 3 months,Thefinalboardedatrain to Leeds.lwas verymui:h iinpressed by closingdatethisyear the beautifulcountryside, as itwas myfirst visit to the UK. isSONovember On arriving,lwas givenawarm welcome by Dr Richard Barton.He introducedme to otherlab oersonnel who zOO2.SeeSGM usethis methodto type C. parapsilosisstrainsto were equallywarm andf riendly,Therefore, working in websiteforf ull details determineif there was anv horizontal transmission of the mycologyresearch laboratorywas a pleasure. andan application infectionand also to deteimineif there was any specific form, The objectiveof my studywas to do molecular strainthat predominatedin the colonizedneonates. A typing on Candidaparapsilosis isolates f rom a neonatal new probe,Cp3- 13, was usedwhich is very efficient as intensivecare unit, Greater numbers of low-birth- it hasa highlevel of discriminationand reproducibility weightinfants now survivein neonatalintensive care andthe resultscan be subjectedto computeranalysis, units(NICU) because of the introductionof new My aimwas to type as manyisolates as possiblein the medicaltherapies.Unfortunately, the survivalof these limitedperiod of 3 monthsand that provedto be quite infantshas beenassociated with an increasein the challenging, incidenceof disseminatedcandidal infections. One of Molecular typi ng revealedpossible nosocomial the reasonsis that cellular immunity, which plays an transmission.The results suggest exogenous im portant role i n protection against f un gal infections, is acquisitionof C.parapsrlosis The mechanismof almostnegligible in neonates,Also, these infants are transmissionmay have been by indirectcontact via subjectedto broad-spectrumantibiotics and prolonged the handsof hospitalpersonnelorfromthe hospital hospitalization,using adhesive tape to fixvenous environment.Also strains from multiple sites within catheters,endotracheal tu bes and monitoring the sameindividual were different,The datastill has electrodesthat stripthe skinon removal,thereby to be subjectedto computeranalysis, increas in g vuI nerabi Iity to f un gal infections, RIGHT: I enjoyedmy stayin Leedsimmensely as the research premature Candidainfectionscommonly seen in neonatesare A neonateinthe work wasvery enjoyable and challenging.I am grateful intensivecare unit. Note the large usuallysuperficial lesions of the mouth(thrush) and to ProfessorE.G.V, Evans, Dr RichardBarton and numberoftubes and attachments rashesof the perianalandgroin regions. Sometimes, DrA.Chakrabartiwho made it possiblefor mero come PHOIOALECK deep-seatedinfections may also be present,Candida f rom lndiaand carry out this research.I am indebtedto albicansisthe mostf requentlyisolated species, but the SGM (lnternatibnalResearch Fellowship) for the proportionof non-albicansspecieshas increased ABOVE: theirgenerous financial supporl, Theyeast Candida parapsilosis. recently.C. parapsilosisisisolated particularly in the Ihecells are characteristically caseof neonates.ln fact,it representsthe second I D r Ro m a Batra rb SeniorSci e ntist at Med i probe elongated mostprevalenl C an d i d aspeciescausi n g bloodstream Laboratories, Unit A1,501 Alliance Avenue, PHOTORICHARD BARTOl\l infections.A largenumber oI C.parapsilosis strains Toronto,Ontario, Canada MON 211

m IODAYVOL'p,/AUGA2

-&"- lfyou wou ld like ffi&Gompendiumof environmentalbioremediation dynamicsofcell structure, and on inhabitants;forwhich prophylatic yourname to be Wpotaio Diseases, andhighlights the potential for thesurvival ofmicro-organisms drugsare expensive totake and to SecondEdition furtherexploitation ofthis very areelaborated, Deepsea monitor,and which may be poorly addedto our EditedbyWR, Stevenson, versatilegroup oforganisms. adaptationsinmarine micro- tolerated;andforwhich there is databaseof book R,Loria, G.D, Franc & Throughits17 chapters, 29 organismsaresummarized and novaccine, reviewers,please D.P,Weingartner internationallyrenowned authors thepossibility thatdeep sea alonClewley PublishedbyAPS Press (200'l) discussthephysiology and hydrothermalventsmay have Central PublicHealth comolete the book US$49,00,pp.144 chemistryofa variety of organic beensuitable sites for the origin LaboratoryColindale reviewerinterests ISBN:0-89054-275-9 andinorganic pollutant oflife discussed. Mostof the formnow available transformations,Notsurprisingly contributorsarenot onthe SG M Tothose with an interest in severalauthors include discussion microbiologistsbutphysical potatoesorplant pathology, this ofthe ligninolytic properties ofthe scientists.Asa consequence we w.Tfi*t?:*11":'" website. bookis invaluable and, thankfully, wood-degradingwhite-rot f ungi, learnmore about problems than Mechanismsand competitivelypriced.lt is a exemplifiedby P h a n eroch aete aboutsolutions. lf we wish to find Gonsequences. A classified substantialupdate onthe chrysospai um,providin gvaryin g outmore about organisms of Advancesin Molecular andGellular compendiumof firstedition and includes amountsofdetail on the specific theabyssal depths, thehigh comprehensiveinformation on enzymesinvolved. Thishas stratosphere,orperhaps the outer Microbiology,Uol. 1 bookreviews f rom diseasesanddisorders inevitablyresulted inthe reachesofthe Universe, we EditedbyM.Wilson 1996 tothe worldwide.The expanded useof duplicationofinformation across cannotknow too much chemistry PublishedbyCambridge presentis also colourphotographs ishelpful, as somechapters. However, other orphysics. Not an easy read, but UniversityPress (2002) nomeans neglected, highlyrecommended, S60,00/US$90.00, pp.328 availableon the isthe language andstructure, fungiare by -80107-9 whichensure wide accessibility, withthree chapters devoted to lDavidLloyd ISBN:0-521 website, Diseasesofmicrobial origin are thefungaltreatment ofmetal- Cardiff University wellcovered and upto-date, but containingwaste materials and About20 years ago, there was a brief.This isnot a book of thelast two chapters focussing spateof books and symposia on methodsorrecipes, more an onthe potential ofmycorrhizal bacterialadhesion and overallpicture or an easy entry fungiinsoil remediation. @Ilfi,"'flfl[,n'[l*identificationofspecific bacterial intonew areas, I was particularly Recommendedtoanyone (not BritishMedical Bulletin, adhesinsandthe host struckby a detail inthe justmycologists)with aninterest Uol.58 macromolecularreceptors to introductionconcerning the inthe expanding fieldof Editedby R,A,Weiss, M,WAdler whichthey bound. Since then, denunciationofpotato environmentalbiotechnology, &S.L. Rowland-Jones thingshave moved on with an consumptionfrom some Scottish lVickiTariq Publishedby0xford University increasingappreciation ofthe pulpitssoon after its introduction. The Q,ueen's U n iversity Press(2001) considerablerange and diversity Fromthis rocky beginning, Belfast $40.00,pp.223 ofadhesins produced even by a potatoeshave gone on to become ISBN:0-19-922486-2 singlebacterial species, andof Scotland'sfourth most important themultifarious physiological and crop,ltwould beinteresting to d&eiologicalsystems Thiscollection of12 excellent geneticmeans oftheir regulation, reflecton how the current debate WUnderExtreme essaysreflects contemporary 0feven greater significance isthe just onG M crops isviewed inthe t Gonditions:Structure studyand understanding ofthe realizationthat we are not futureor whether they will have andFunction. Biological virusand disease ofAlDS. Each talkingabout binding, but about similarimpact oracceptance. andMedicalPhysics reviewisconcise and informative, interactionsothat the responses lGerrySaddler Series andthe book as a whole is highly triggeredinthe host cell by ScottishAgricultural EditedbyY. Taniguchi, recommended.Almost all aspects bindingofbacteria (and vice ScienceAgency, H.E.Stanley &H. Ludwig ofthe subject are covered from versa)are of central importance Edinburgh PublishedbySpringer-Verlag theevolution ofthe virus and its inpathogenic processes, This (2004 interactionwiththe host cellto bookisa collection of13 69,95/sFrll6.00/$49.00/ theglobal economics and independentreviews, each of a Fungiin US$74.95,pp.282 epidemiologyofAIDS. The standardroughly ofwhat might Bioremediation. ISBN: 3-540-65992-7 pathogenesis,prevention, appearinMicrobiology or BritishMycological interventionandmanagement of MolecularMicrobiohgy.lt isthus SocietySymposium lfoundthis a most interesting AlDS are all discussed. Indeed, acompact source ofinformation Series,Uol. 23 andinformative volume, lt thediversity ofthe topics that are onthe current state of the art in a EditedbyG.M, Gadd encompassesthephysics of addressedminors the myriad selectionofbacterial-host PublishedbyCambridge waterat low temperature, the problemsand concerns that arise systems. UniversityPress (2001 ) behaviourofproteins under froma virus that devastates the IRoyRussell S80.00/US$120,00,pp, 481 extremepressure asstudied by immunesystem; that is spread Un ive rsity of Newca stl e ISBN:0-521 -78'119-1 NMRand FTIR spectroscopy and sexuallyandthrough blood X-rayscattering, melting contact;that mutates extremely This23rd volume ina well- temperaturedetermination and rapidly;that has disproportionately respectedseries of symposia stopped-flowenzyme kinetics. affectedtheless developed providesanoverview ofthe Theeffects ofpressure on nationsand their poorer currentstatus offungi in haemoproteinintramolecular electrontransport, onthe

VOL2g/AUG02 F I' l'

llmmunologyof toprovide aselection oftopics Chapter4,which proved mildly lsecretAgents: reader,however, isthe bias Ulnfectious Diseases theyregard as' at the forefront initating.Researchers maybe TThe Menaceof towardssystems used in EditedbyS.H.E, Kaufmann, offun gal cell biohgll.The volume disappointedthatsome EmergingInlections Americanlaboratories, which A,Sher& R,Ahmed isdivided (unnecessarily) into bibliographiesdonot contain a ByM, Drexler isparticularly marked inthe PublishedbyAmerican Society twoparts, The first covers growth higherproportion ofreferences to PublishedbyJoseph Henry Press/ discussionoflaboratory forMicrobiology (2001) (hyphal,yeast and colony), post-1995literature. NationalAcademy Press (2002) informationsystems, although it US$115.95,pp.520 morphogenesis(in Can dida Apity this text is so expensive, S17.95,pp.316 isless so in other subject areas -55581-21 ISBN:1 4-7 albican$and pathogenicity (of sinceit representsauseful source ISBN:0-309-07638-2 covered,Although laboratory plantpathogens), whilethe ofinformation forundergraduates technologycontinues toadvance, Thereare a large number of second,entitled' Stru ctu ral aswell as their teachers and Severalrecent books have dealt thisbook should prove valuable immunologytextbooks available, Contin uu nl,provides anoverview researchers.Recommended for withemerging infections and forcomparing themerits of newer mostof which devote only one ofhydrophobins, various cellular purchasebyacademic libraries, futuremicrobiological threats, For systemswith those currently chaptertothecontrol of components(including thecell lVickiTariq thelay reader or student, .Searef available,Thisbook should infectiousdiseases, thereason wall,microtubules andvacuole TheQueen's University Agentsisoneofthebest. There is interestallthose involved inthe whytheimmune system evolved systems),andfungal genomics. of Belfast alsosomething tolearn forthe practiceofclinical microbiology. inthe first place, while the Individualchapters are supported professionalmicrobiologist, lAlanlohnson remainderofthe book discusses byextensive andup-to-date thoughnottoo much, Madeline CentralPublicHealth variousmalfunctions or bibliographies,Thevolume iswell Drexlerwritesagood story line LaboratoryColindale unfortunatemanifestations ofthe illustratedandcertainly realizes lflrxi?'lxtlfiiil,whichisscientifically accurate system,such as autoimmunity theprimary aim oI'The Mycotd, Stresses.Physiological, witha minimum oftechnical andallergy, This multi-author namelytohighlight developments Biochemicaland jargon,Moreover, sheis bang lnn lllustrated bookattempts toexpand upon inboth basic and applied research MolecularMechanisms up-to-datewith a chapter on the UGuidetothe thosesingle chapters andto fill intofungal systems. EditedbyL,C. Rai& J.P, Gaur issuessince last September and Protozoa,Second thegap between immunology Recommendedforpurchase by PublishedbySpringer-Verlag theanthrax scare that followed, Edition.0rganisms andinfectious disease text institutionallibraries, butrather (2001) Yetshe observes, 'Themost TraditionallyReferred to bookswhich concentrate onthe priceyfor most individuals. DM383,064Fr329,56/S1 32,00/ ceaselesslycreative biotenorist is as Protozoa,or llewly pathogenorthe disease caused. lVickiTariq US$194.00,pp.421 stillMother trlature. Her microbial DiscoveredGroups Thebook succeeds inthis aim, TheQueen'sUniversity ISBN:3-540-41938-1 operativesareall around us, ready EditedbyJ.J, Lee, G.F. Leedale andshould be a valuable resource of Belfast topounce when conditions are &P, Bradbury foracademics andgraduate Thisisan interesting bookthat ight.From airborne anthraxto PublishedbySociety of studentsworking inthis area, suffersfrom an effort to Westtrlile virus, from the deadly Protozoologists(2000) andfor undergraduates in 1|fne Mycota.A generalizephysio log ical organismshiding in ourfood to US$135,00,pp,1,432 immunology,ltis, however, UGomprehensive respttnsesttver aset of organisms thenext, inevitable flupandemic, ISBN:1-891276-22-0 probablyalittle too specialized Treatiseon Fungias (thealgae) thatare not we'reup against aperpetualwar formedicalstudents or ExperimentalSystems phylogeneticallyrelated withgerml. Thislong-awaited bookis undergraduatesinmicrobiology, for Basicand Applied (paraphyletic).Somechapters lRobinA.Weiss,UCL enormouslydisappointing. The asa certain level of understanding Research.Uol. X: dealwiththis problem by publishersstarted taking people's ofimmunology would be required IndustrialApplications restrictingtherange ofthe moneyin1995;the titlepage Editedby K. Esser &J,W. Bennett review,while others sail blithely tomake use of thisvolume. t 1|Manud of givesthe publication dateas lAndyHeath VolumeEditor:H. D.0siewacz onregardless. Thetopic of stress UCommercial 2000,but it hasonlyjust appeared Un iversityof Sheffi el d PublishedbySpringer-Verlag coversboth the concept of Methodsin Glinical (February2002). The most recent (2002) organismsgrowing outside their Microbiology referenceI could find was 1998. DM425.86/sFr367.01/$1 47.00/ normalcomfort zone as well as EditedbyA,L. Truant Thisisan hugely exciting time lfne Mycota.A US$199,00,pp,414 howthegroup(s) generally deal PublishedbyAmerican Society tobe involved inprotistan UComprehensiue ISBN:3-540-41583-1 withenvironmental extremes, forMicrobiology (2002) systematics,withnew ideas Treatiseon Fungias particularlynutrient deprivation, US$115,95,pp.502 appearingsofrequently, but ExperimentalSystems Thelatest volume inthis series Here,however, afocus on the ISBN:1-55581{89-2 consequentlytheuseful life of for Basicand Applied providesanoverview ofboth photosyntheticproperty that suchtexts is around 5years, This Research.Uol. Ulll: traditionalandnovel industrial makesthem algae does not TheEdito/s stated aim was onehas been so long in Biologyol the FungalGell applicationsoffungi, from their alwayslead to a clear picture. toprovide anoverview of productionthatmost of that EditedbyK. Esser rolein the production ofbread, Wenow realize that an awful lot of commerciallyavailable manual lifetimehas gone. Final VolumeEditors: R.J. Howard cheese,fermented foods, beer themicro-algae are,in fact, andautomated testsystems submissiondates for the chapters &N.A.R. Gow andwines, totheir potential in mixtrophictosome degree: availableforuse in clinical wouldhave been ausefulguide PublishedbySprin ger-Verlag bioremediation.Theformer topics dealingwith nutrient depletion microbiologylaboratories, Despite forreaders. The book has grown (2001) arecovered inthe first three froma strictly botanical theenormity ofthe task, this book totwo volumes, largely because DM318,86/sFr274.99/$11 0.00/ chapters, which include summary perspectiveisnot always byand large achieves its thelayout is in large type, and it US$l59.00,pp,307 flowdiagrams that teachers and appropriate,Don't get me wrong; objective,Twoparticular looksamateurish, Editorial ISBN:3-540-60186-4 studentsalike willfind useful. Ten theauthors have provided an strengthsare thejudicious use of productionstandards are ofthe remaining 18chapters extremelystimulating setof welllaid-out and informative disappointing,lfyou are in the Tocover the biology ofthe reviewthewide diversity offungal reviewsand I ampleased tohave tables,and the inclusion ofa large field,you need to have access to fungalcell comprehensively metabolitesandenzymes, Editors thisbookonmyshelf, numberofphotographs which it,but it could and should have withinasingle volume would be a offuture volumes maywish to lDaveRoberts greatlyaid understanding of beenso much better. dauntingtask, and in fairness to addresstheoveruse (and on TheNatural History equipmentortests that the reader lDaveRoberts theEditorsthey donotattemptto occasionsmisuse) ofbold MuseumrLondon maynot be familiarwith. ()ne TheNaturalHistory dothis, Rather their aim has been typescriptinsome chapters, e.g, drawbackforthe non-American Museum,London

sN$sNsw$s*ssYroDrv voLn/ NJG02lE dboun Microarrays: syndromeofAIDS, criticismisthat the book isUS- replicationfunctions aswell lninciplesand WGene Expression Thisvolume concentrates on centred,perhaps betraying the asvirus-cell interactions, UPractice of Glinical Applications.Principles viralco- orsuperinfections ofHIV- author'soriginal intention towrite pathogenesisandvaccine Parasitology andPractice infectedpatients, mainly due to ahistory ofWendellStanley and development,Thequality of the EditedbyS.H. Gillespie & EditedbyB.R. Jordan humancytomegalovirus, hepatitis theVirus Laboratory atBerkeley. presentationsisexcellent. This R.D,Pearson herpesvirusThework of Bawden and Pirie and bookshouldbestudied byevery PublishedbyJohn Wiley & Sons PublishedbySpringer-Verlag virusesA-C, human 'RNA (2001) type8, Epstein-Barr virus, and ofthe Tiibingen group is virologistibut the intricate Ltd(2001 ) 42.95/sFr81,32/S31.50/humanpolyomaviruses, Whilst describedlargely interms of its replicationstrategies andother S175.00,pp.670 US$49.00,pp,140 HIVinfection can substantially interactionwithevents in featuresofthese viruses are of ISBN:0-471-91729-2 ISBN:3-540-41508-4 acceleratethenatural course of Stanley'sgroup, but much other generalinterest toall virologists. infectionwith the otherviruses, workdone outside the US gets Althoughthe price ofthe book is Thisimpressive volume draws Theauthors have provided a theintroduction ofhighly active shortshrift.Neveftheless, itis relativelysteep, it is worth the onthe expertise of44 specialist cunentpractical guide and review antiretroviraltherapy has reduced fascinatingtoread aboutthe expenseandis highly authors,togive a comprehensive ofgene expression analysis using viralopportunistic infections. circumstancesthatpropelled recommended. overviewofparasitology, The DNA microanays. Thevarious Theindividual chapters researchinpafiicular directions aUrich Desselberger bookbegins with a historical approachestoD NA microanaying concentrateonsome ofthe atdifferent times, and I Addenbrooke'sHospita l, account,fascinating inits thisbook to anyone Cambridge descriptionofparasitology's aredescribed indifferent naturalhistory and epidemiology recommend 'golden chapters,including glass slide ofthe co-infecting viruses, but whois interested inwhy science ageibetween about 1850 DNA microanays, oligonucleotide mainlyon clinical presentation, proceedsinthe way it does, and1930. The subsequent chipsand nylon membranes. diagnosis,prognosis, JDavidRobinson fiProtocols in epidemiologychapter emphasizes Theexamples andprotocols managementandantiviral ScottrcftCropResearch Vlichenology. howfailure toundentand this aremostly based onworkwith treatment.Resistance toantiviral Institute,Dundee Gulturing,Biochemistry, disciplinecanlead to counter- eukaryoticorganisms butmany drugsand their side effects are Ecophysiologyand Use in productivecontrol measures, and proceduresaregenerally reviewed.References areup-to- Biomonitoring alsoexplains thevalue ofnew applicabletoresearch inthis field. dateto approximately 2000. The 6frne l{idouiruses Editedby l. Kranner,R.P. Beckett technologiessuchas satellite Thereisa very useful chapter on researchprogress inthis area is lF [Goronauirusesand &A.K.Varma imagingand computer mapping, [)NAmicroarray data analysis and fastas, for instance, the data on Arterivirusesf PublishedbySpringer-Verlag Theremainder ofthe book (2002) awealth of references tohelpful co-infectionwith H lV and G B Editedby E. Lavi, S,R, Weiss & consistsofthorough and lnternetsites and published virusC fnglJ Med (2001) 345, S.T.Hingley DM21 3.894Fr184,04/S74.00/ thoughtfuldisease-specific [fl pp,580 literaturethroughout thebook. 701,715,7611testify. PublishedbyKluwer Academic US$'109.00, reviews,beginning (naturally) Individualorganizations aswell as Thechapters arewritten by (2001) ISBN:3-540-4ll39-9 withmalaria. Many chapters individualsarelikely to find this teamsof clinicians and scientists. us$l45.00/sl01.50/166,75, includediscusions ofthe bookauseful resource forsetting Inmy opinion, thebookwill pp.742 Thisisa welcome addition to emergingrole of new molecular upand working with D NA benefitmainly busy clinicians of ISBN:0-306-46634-1 theseries because lichenological diagnosticand typing techniques, microanaysinthe laboratory. allspecialtiesasHIV infection has methodsare seldom documented lwouldlike to see future editions phycology Thebook is up-to-date with nowestablished afirm place in Thevirus families Coronaviidae intexts on mycology, or includemore thematic chapters, plant developmentsinthis field and thedifferential diagnosis of andArterivi i daehave recently science,Methods described suchas parasites inimmuno- describesfuture trends. However, diseaseinpractically allareas beenbrought together inthe arewide+anging, mostare lab deficiency,orchemotherapeutic procedures, thistechnology isdeveloping at ofmedicine. t orderl,lid ovi ral esThis book butsome are field- agents.Nonetheles, thisis an afast rate and it ispossible lUlrich Desselberger describestheProceedings ofthe basedormore applicable tothe excellentbook, suitable for every p thatsome ofthe approaches Adden b rooke's Hospital, fithI nternatio nalSym osi um o n herbadum.Instructions aremore microbiology/infectiousdisease permisible describedinthe book may be Cambridge Ilidovi rusesheld inPennsylvania explicitthan is usually department,andfor individuals paper, supersededinthe nearfuture. inMay 2000, These viruses ina research andinclude witha particular interest inthis aterryWells havecomparatively verylarge usefultips,wamings ofpotential intriguingspecialty. Un iversity of East Ang Ii a dhfne life of aUirus: genomesofsingle-stranded RNA pitfalls,and sections on lAodhdn Breathnach and lnstituteof Food WTobacco Mosaic ofpositive polarity (13-32 kb), troubleshooting.Asthe Editors StGeorge'sHospital, Research,Norwich Uirusas an Experimental andthus handling ofthese pointout, the manual isnot London Model,1930-1965 genomes,aswell as disection exhaustive;forexample, itis ByA.N,H.Creager oftheirfunctions, isnot a trivial publishedalmost simultaneously &Uiral Go-infections PublishedbyUniversity of exercise,Thehighlight of withanother dedicated to lnlos inthe Modern Uin Hlu:lmpact and ChicagoPress (2002) thismeeting was the presentation methodsinlichen biomonitoring, UWorld Management. H/BUS$75.00 19,47.50; ofsuccess inobtaining infectious atopic restricted tothree chapten Byl.E.Alcamo Stateof the Art Series P/BUS$27.50/S16.00, pp.352 cDNAclones ofseveral here.Nonetheles, thispleasingly PublishedbyBlackwell Publishing Editedby J. Lalezari& G.Moyle ISBN : H/B 0-226-12025-2t IIidovi nlesby research groups in producedvolume isa creditable (2001) PublishedbyReMEDICA P/B0-226-1 2026-0 Germany,Spain and the United startingpoint. lt is esential $18.95,pp.90 Publishins(2001) States.This achievement will buyingfor lichenologists and ISBN:0-632-04414-8 $20,00,pp.144 Whenthe'centenary'of greatlyimprove further study of deservesaplace in institutional -901346-40-4 was thisexciting group ofviruses librarieswhere it might tempt Thisbook states its aims to ISBN:1 tobaccomosaicvirus flMV) 'present celebratedin1998, attention thathave various pathological mycologistsandphycologists to principlesofthe AIDS Co-infectionswithviruses and wasdrawn to the many scientific presentations(infections and extendcomparative studies to epidemicina format that is easy othermicro-organisms area advancesinwhich ithas been diseaseofthe gastrointestinal and includelichenized species, and tounderstand andcomfortable crucialfeatureinHIV infection: involved.This book attempts to respiratorytracts,ofthe CNS, wherestudents will find it useful toreadi lt usessimplistic format, vasculitis,etc).The book isa forprojectwork, witheach chapter introduced bya indeed,many ofthese secondary describehow TMV came to hold 'Review infectionsdefine the clinical suchaprominent position asa treasurefordetails on various lPeterCrittenden andPreview' section modelsystem. Anobvious Un iversity of Notti ng h a m

W WEffiWffiW.ffiffi&WIODAYVOLN/ AUGU2 I L (akaasummary), keysentences dffiEnzymesinthe pathogensbrought about itwillundoubtedly become an manycontributors draw on their inblue ink and three questions WEnvironment. bygenome sequencing and importantresource to students, directexperience ofthese presentedatthe end to focus the Activity,Ecology, and genomics.Eachchapter on courseorganizers andyoung problems.Boththe risks and readeronkey learning points. Applications individualpathogens now scientists, benefitsoffermentation arefairly Whilethe layout may meetthe Editedby R.G. Burns &R.P. Dick containsashort biography ofthe llrina R.Tsaneva representedinthe book, although objectivesofthe author, the PublishedbyMarcel Dekker Inc organismatthe beginning and a UniversityCollege lwassurprised tofind nothing contentisconfusing - is this a text (2004 usefulsummary outline ofthe London specificon possible contributions bookor not? Basic virology and US$195,00,pp,61 4 informationinthe chapter atthe offermentation tothe welfare of immunologyisdescribed which ISBN:0-8247-061 4-5 end,so students will really find &t'titrltication and weaninginfants and lactating (stated thelay reader target thisbook invaluable toaugment WDenitrification in mothers.Chapters onwttrms, audience)willfind hard to Thistopic iscertainly ripefor lecturenotes and to revise from, etc,,and endogenous chemical (Jne the ActiuatedSludge assimilateand relate to the H lV thecomprehensive treatment ofthebestfeatures ofthis Process.Wastewater hazardsare very welcome, The presented, scientificinformation deliveredhere, asthere has been bookisundoubtedly the MicrobiologySeries clearpresentation, usefultables Currentissues inHlVare notwell littlesince Soil Enzymes extremelyreadable textwhich ByM,H. Gerardi anddiagrams andstriking (Academic covered,rather the history of the Press,1978). Enzymes hasbeen written ina very Publishedby John Wiley & Sons illustrationsofparasite life cycles epidemic.The lay person with an inthe Environmenfgoes much personaland communicative style Ltd(2002) willmake this book an asset to interestcould access asimilar furtherinits21 chaptersfrom whichmaintains the interest of 937,50,pp,193 mostfood-related courses but its standardofHIV/AIDS knowledge contributorswhoattended the thereader, The numerous figures ISBN: 0-471 -06508-0 pricewill limit its sales to LDCs, fromreading newspaper reviews, conferenceofthe same name in arealso excellent andmany lBriant.B.Wood JSheilaM. Burns Spainin 1999.lt is, however, not havebeen retained from the first MikeGerardi's synthesis ofthe Un ive rsity of Strathclyde Regional Clinical 'proceedingsl merelya butis much edition,Insummary thisis a fieldis commendable with a very VirologyLaboratory moreauthoritative andordered, fantastictextbookwhich willbe accessible,if brief, overview of Royal Infirmaryof Thebook sets off with three long usefulfor undergraduates ffiUicrobiology and thetopic and then a detailed libraryGD Edinburgh chapterscovering enzymes in postgraduates WUideo soil, alike, examinationofthe processes ByA.J. Cann lakesand the sea - heavily lDaveKelly froma theoretical, operational PublishedbyDepartment of referencedand detailed. Chapters Un ive rsityof Sheffiel d &Human andtroubleshooting perspective Microbiologyandlmmunology, &Iitusts ofvarying length follow, dealing wursease thatwill be of benefit to students UniversityofLeicester (2002) withmore ByJ.H. Strauss &E.G. Strauss specifictopics Principlesol andpractitioners alike, While us$75.00 (rhizosphere,biofilms and PublishedbyAcademic Press WGene Manipulation,theinclusion of the Gram stain Toorder, see http//www-micro,msb, (2002) myconhiza,forexample) and SixthEdition procedureasan appendix does (bioremediation, le,ac,uk/video/cd,html S32.95,pp.383 appliedaspects ByS.B. Primrose, R,M, Twyman notreally add to the context, the biosensors,biocontrol). Thefinal ISBN: 0-1 2-673050-4 &R.WOld consistentlack of Sl unitsin the TheCD contains basic chaptertakes us back to the PublishedbyBlackwell Science calculationsforplant loading comprehensivemicrobiology fundamentalsofenzymes insoil Thisbook isone of the best (2001) parametersisthe only significant informationonover 300 topics. tofinish off this large book in good generalvirology texts I have seen. S27.50,pp.390 short-cominginan othenruise well Includedinthe CD price is a site style,The Editors and contributors Thedetailed andyetvery user- ISBN:0-632-05954-0 writtenand presented text, licencefora LAN or Intranet. havestuckto the taskwell and friendlystyle, taken together with Donald Reid 0nthe positive sidethis is the thereisno doubt that this is a itsreasonable price means that it Eventhough anew edition has WaterSeruicesUnit, firstUK example ofa general referencetextfor libraries willverylikely become apopular longbeen overdue, thecunent Scottish Executive, CDmicrobiology teaching aid. everywhereand, in that context, ' studenttext. Having said that, the popularityofthis book is proof Edinburgh Particularlyimpressive arethe goodvalue for money. bookwillalsobevery usefulto forenduring success among its widevariety of easily downloaded moreexperienced researchers lAIan McCarthy audience,Theauthors areto and highquality images and short wanting Un iversity of Liverpool d&Fermentation aconcise summary ola becongratulated fortheir Safety QuickTimemovies. These may be field virology WFood of outsidetheir own, courageouseffortto bring the ByM,R. Adams & M,J.R.Nout particularlyuseful for staff to use Thebook describes viruses of newedition upto-date inan area Published inPowerPoint lectures and for plants byAspen Publishers bacteria, andanimals but thatis a technological hallmark (KIuwerAcademic) (2001 studentpresentations, However, focuses ffi3lfils['11,.,,,, ) onthose causing diseases A MolecularApproach, ofthe 21 st century, The book has 156,50/US$1 38,00/S95.50. thepurchaser must be aware that inhumans, pathogenic SecondEdition beenrevised throughout covering pp,300 the'so-called'onlineresources mechanismsandthe use of ByA.A,Salyers &D,D.Whitt moderncloning vehicles and ISBN:0-8342-1843-7 arenothing more than online virusesinattempts totreat PublishedbyAmerican Society technologies,fora wide range of marketingforbook purchases. disease,Thenumerous tables 'Wholefood' forMicrobiology (2001) organisms.ltnow includes an enthusiastsoften Addto this the rather amateur andfigures are very clearwith U5$56,95,pp,560 expandedchapter onsome assumethat'natural' fermented packagingandunattractive extensiveuseof colour, This book ISBN:1-55581-171-X importantapplications ofgene foodsare intrinsically safe, This is homepage,thereis certainly isdesigned tobe an overview of technologies.lt iswell structured adangerous myth, but existing roomfor improvement; an virology,however, extra Thefirst edition ofbacterial andeasy to navigate, The starting textson food fermentations do accompanyingbookletfor referencestomore specific and pathogenesisproved tobe an levelisstillwellsuited to littleto correct it, I therefore exampleisa must. These detailedarticles atthe end of extremelypopular textbook with advancedundergraduates, butit welcomethis authoritative text criticismsaside, this CD provides eachchapterwould behelpful, itsclear explanations, excellent quicklyleads tospecialized editedby two experts with an auseful source ofinformation for Despitethis, I cannotrecommend diagramsandsummaries. This sophisticatedtechnologies and impressivepanel of authors from bothstaff and studentswho might highly, thistext more secondedition has been applications,Some ofthe material industry,academia and othenruisehaveto rely on the lChristopherRing theWH0. extensivelyre-written inmany willbe a challenge tobeginners. lwouldhave valued a contribution questionablequalityof much GlaxoSmithKlineR&D, ()verall, areasand updated totake thescientific content of froma developingcountry, where Internet-basedinformation. Stevenage accountofthe revolution inour thisbook is seriously impressive, traditionalvillage f ermentations lloyPerkins understandingofbacterial itscoverage comprehensive and canpresent problems, However, Hudde rsfi eld Un ive rsity

t" Addrcss

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Confusionover bovinetuberculosis in badgerc,Gattleand humans?

TB wasvirtually Progress in politics and scienceoften happens by the lesions are usually confined to the thorax, eradicatedfrom serendipity and an unexpected effect ofthe 2001 foot- indicating transmission by inhalation, it is hard to cattlein the UK by and-mouth epidemic will be on bovine TB. The routine seehow badgers could passTB to cattle. testing ofcattle and the badger culling trial were both the 1970s, apart Transmission via ingestion is revealed by lesions suspended for over 10 months, so cattle TB will be fromsmall areas in in lymph nodes of the head and neck or around the much worse, the badger trial has been compromised SWEngland, gut. But the infective dose needs to be up to a million and the risks to public health will have increased. Before Transmissionfrom times greater than by inhalation. Cattle thus may be considering these issues,it is important to understand badoerswas at little risk even from pasture highly contaminated that the justification for the controversial badger culling blarn'edforthese with cattle faeces.IJnfortunately, many studies of part of the cattle TB eradication programme depends on andacontroversial 'accepted both cattle and badger TB lesions present uncritical four main claims which have become wisdom': government- accounts of the wide range of sites, but fail to fundedculling trial 1 the S\W England cattle TB problem is due to its distinguish the primary sites which indicate route beoan,The BSE higherpopulation ofbadgers than in the rest ofthe of infection, and secondary spread. The pivotal criSisof the lateBOs UK; misunderstanding about badgerTB is that it'lr andearly 90s ledto 1,;.badgers cause 80-9O % ofTB outbreaksin cattle 80 % aia tbe respiratory rlute' ,whereas it often starts in cutbacksin proven herds; the submandibulars and is clearly of dietary origin, measuresof :-1.TB is transmittedfrom badgersto cattle,not vice e.g. when the animals are worming under infected cow pats. Transmission from cattle to badger is far controllingbovine VCTSA; 'work' more likely than viceversa. TB andthe recent 'i badger culls in reducing cattle TB outbreaks. foot-and-mouth Returning to claims for badger'guilt', the protocol for In fact none of these claims stands up to scrutiny. outbreakled to the attribution of the source ofTB in herd breakdowns leads Much of the confusion over TB has arisen because in practice to looking at other cattle or badgers, since suspensionof veterinary students no longer have a solid training in other domestic stock, wildlife or human sources^re t^re. testing,TBin cattle diseasepathogenesis and the classic studies by Francis However breakdowns are often ofuntraceable origin, rsnow flsrng ano in the I940sand 1950s have been largely overlooked. spreadingrapidly. e.g. 69 7o tn Cor nw alI (I97 2-B), 7 6 % in | 99 3 in the Are badgersreally Cattle TB is a slow but progressive bronchopneumonia non-SrW and, even with a fully computerized cattle to blame? which has two pivotal implications: database,32% inUlster. Blaming badgersformost breakdowns hence overlooks the'undisclosed' cattle i An'undisclosed reservoir'.The long incubation reservoir and that the badgers found with TB have and progressionfrom microscopic or non-visible merely caught it from cattle. lesions (NVL) to tubercle lesions visible (VL) at abattoir inspection may take ayeat ot so. Hence, Likewise, badger culling since 197 5 has failed to prevent early'latent carriers'may be NVL, non-feactofs to the current cattle TB crisis, with spread from the SS7 to the skin test and not very infectious. This explains Midlands areaswhich had been TB -{ree fot 40 years. why annual testing is the gold standard worldwide: The casesof badger culls'working'often cited overlook it removes TB casesbefore they can passon the the simultaneous removal ofthe'undisclosed' cattle diseasewithin the herd or to other herds if stock is reservoir. For example at Steeple Leaze,Dorset, where sold. Repeat testing may be needed to weed out there were up to five cattle TB tests ayear in I97 3-5 , latent carriers asthey come on stfeam. Switching to 244 reactors were removed from the cluster of farms, a longer herd test intervals of 24 yearsmay simply third being VL, so curing the chronic problem with just allow TB to build up within herds, and carriers to one reactor found in 197 6-7 . Culling badgers be exported before TB is diagnosed and movement subsequently was irrelevant. restrictions imposed.

l. Transmission. Francisdrew acleardistinction euCattleTB crisis between primary and secondary lesion complexes. A century of experience of cattle TB schemes Cattle TB may be transmitted almost entirely by worldwide suggests that successdepends on annual the respiratory route with lesions in the pulmonary testing of ALL cattle, and since the test is only 80 % ffi Pleasenotethat lymph nodes appearing before those in the lung accurate, a movement ban from TB areasis the only viewsexoressed in tissueswhich they drain. As these lesions grow, guaranteed way ofpreventing spread to TB-free areas. Commentdonot bacilli shed into the blood may set up secondary Britain had a textbook scheme with the whole country necessarilyreflect lesions in other lymph nodes and sites, including under attestation by 1960 a low point by I97 of officialpolicyof the liver, kidneys, brain or bone. Since early on in TB ,and 9 SGM Council. only 89 herds infected and 600 cases.\Working from 135 herdshavebeen LEFT: lost in trial areasand Astorm brewing over farmland in Cornwall,inthe far south t,vest of unrestricted movemenr theUK. ofsome 700,000 PHOTOIANATHERTON replacement cattle untested for TB musr invalidate the data. Badgerculling should have ended years ago for four reasons. north to southhad reducedTB to a few high density ie] It is basedon flawedscience, as already discussed. cattle'hotspots'inthe Snfl.Depopulating rhese would Much ofthe rationalecomes from MAFF's high probablyhave eradicated TB but the Ministry of densitybadger study in Nfoodchester.These data Agriculture, Fisheriesand Food (MAFF)was havebeen used to makecomputer models in which jn overstretchedat the height of the BSEcrisis 1992*3, TB is supposedlyendemic and self-sustaining and solongerTB testintervals were introduced with fewer lacksoutside inputs from cattleor other sources. cattle tested,and there were massive stock movemenrs. Thesemodels aim ata prevalenceofTB of lI-22 % S\Wherds with TB nearlydoubled from 12I to 232 in badgers,overlooking the reallevels which areoften and therewere new outbreaks on Exmoorand in substantiallyhigher. Therefore, whilst TB was $Torcestershire.By l999,over 10 7oo{new breakdowns confinedto a few socialgroups ofbadgers for years, were in areasTB-free for 10 years,including Avon, the cattleTB outbreaksin the 1980sand 90smeanr ry Cornwall, Devonand even in'frontier'counties such as that the diseasespilt overto new badgerclans. Badger Derbyshire,Shropshire and Staffordshire. Statistics for TB peaksafter cattle. infectedbadgers show that thesewere unlikely to be {b}It is uneconomic.An earliermodel suggested the cause.For example,TB wasdetected in oniy 11 out culls did not work andthat the I97 5-6 drop in cattleTB of 1,204 badgerstested in Somersetbetween I97 2 wasdue to Anderson,R.M. & and1993. bansoflrish imports.In I97 5-.83badger (1985). cullscost f9 .7m{or allegedpreventative benefits tewhella,$/. Population dynamics of the S7ith the 10 month suspensionofTB tesringdue off 1.9m,anet loss off7.Bm. All of themethods badger (Melesrneles) andthe to foot-and-mouth,reacrors in herdsarcintodouble suggestedfor badger (cull, control fertility control epidemiologyofbovine figures; restockingh as akeadylet TB into Cumbria and or vaccination)are labour intensive and too costly. tu berculosi s (My coba cter i un Scotland.Ir wouldn't besurprising ifTB hasnor Removingeach badger with TB in the Bournetrial bwis).Philos Trans R SocLond doubledagainfromthe L,031herds and 9,000 casesof " hascost €3t,000 againstanaveragefarmer income BBiol Sci3lO,32l -381. 2000,andwith almostno movemenrrestrictions TB of only 58,200 per annum. And soapart from the Bourne,J. (2 001).An will spreadfar andwide andblight the cattleindustry epi de n iologica I i nuesti gat io n i nto {*} ethicaldoubts over culling a legallyprotected for the next decade. bouinetubercu los is. DEF RA : 3 rd species, Report. www.defra.gov. uk/ animalh/tb/isg @ Riskto human health t*{}as Mclnerney says,'in tbelast analysis tbe problem of badgersand bouinetuberculosis isfundamentally a political Francis,J. (1947).Bw ine Mandatorymilk pasteurizationis normal in cattleTB Lne'. TubercuI os is. London: Staples schemes,as in Scorlandand Ireland. England and \fales Press. 'greenrop' still havesome 400 milk producers,and The unforeseen impact offoot-and-mourh may finally Francis, J. ( 1958). Tuberculosis attemptsto demonstrare conclusively that banraw milk havebeen thwarted politically. catle are the problem, in An imals and Man. London. Iil/ith TB sowidespread there is increasedrisk, and badgers merely innocent bystanders, thus clarifying Cassell. paniculaily to farmersconsuming the home product. decadesofconfusion. Hancox, M. (2000).Cattle TransmissionofTB from meatseems less ofa risk. WMartin HancoxMA (Oxon),l7 Nouncells tuberculosisschemes: control Crosg Stroud, G/oucestershire GL5 | pT,llK, or eradication? Lut App/ S Badger Microltiol3I ,87 -93 . cull trial compromised? has been a member of the Badgers and Bovine Krebs,J. Q997).Bouine The validity of the Krebs/Bournetrial wasopen ro TB Panel. Tuberculosisin Cattle and doubt from the ourser.It is Tel.0l453840146 well behindschedule, farmer Badgers.London:MAFF. co-operationis only 50 % inWest Cornwalland animal Zwckerman, S.(1980). rights groupsinterference with trapshas compromised B adgers,C att leand Tubercu los i s. the results asin Sussexin1986. Bur morecriticallv. some London:HMSO.

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lOTHBIENNIAL ANDCENTENARY ffit$ffi$"i$K*R mmptmrx$:ffiil*RCONFERENCEOFTHECHALLENGER ffi CIRREi11pR0|\|T|ERS|NPARAS|T|CS0CIEIYF0RMARINESCIENCE ACHEMA 2003 :21TH INIERNATI0 NAL ENZYM0I0GY:EMERGINGIRENDSPR0T0Z0A.BRITISHSECTI0N0FIHE Plymouth,Devon EXHIBITION_CONGRESSONCHEMICAL ANDFUTURE PROSPECTS S0ClETY0FPR0T0Z00L00Y(BSSP)9-13September2002 ENGINEERING,ENVIRONMENTAL StMartin's College, Ambleside linnean Society, [ondon C0NTACT:emailchallenger@mail,pml, PROIECTIOl\lANDBIOTECHNOLOGY 20-24August 2002 2September 2002 acuk; www challenge12002 org,uk Franklurtam Main, Germany C0NTACT:TheMeetings 0ffice C0NTACT:HarrietJones 19-24May2003 BiochemicalSociety, 59Portland Place, ([email protected])orthe BSSP UNDERSIANDING THEUSE OF MASS C0NTACT:DECHEMA eV,P0 Box1501 04 LondonW1B 1 QW 0el. 020 7580 3481 ; website(www,bssp.org) SPECTROMETRYINPROTEOMICS, D-60061Frankfurtam Main,Germany Fax020 7637 7626; email AONE-DAY LECTURE COURSE (Tel+49 69 7564 0;Fax +49 69 7564 meetings@biochemistryorg) 201;email achema@dechema,de; PROTEINTECHNIOUES. 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