肠杆菌科e PPT专业课件.ppt

ENTEROBACTERIACEAE,.,1,Morphologyallreducenitratestonitrites;alloxidasenegative.Lactosefermentation:normalflorapositiveandpathogensnegative.Primaryisolationmediaincludeeosin-methylene-blue(EMB)andMacConkeyagar.Differentialselectivemediaforspecificorganismsincludingdyesandbilesalts.(Salmonella-Shigella(SS)medium,bismuthsulfitemedia.),.,2,Classification29genera,over100species.,EscherichiaShigellaEdwardsiellaSalmonellaCitrobacterKlebsiellaEnterobacterHafniaSerratia,ProteusProvidenciaMorganellaYersiniaErwiniaPectinobacterium,.,3,AntigenicStructure,Mostaremotilebyperitrichousflagella-Hantigens.CapsuleKantigen(ViforSalmonella).Cellenvelope(wall)LPS(endotoxin)Oantigen.variousoutermembraneproteins.Pili-variousantigentypes,someencodedbyplasmids,.,4,鞭毛抗原（H）,菌体抗原(O),K或Vi抗原,.,5,septicemia,pneumonia,meningitisurinarytractinfections,CitrobacterEnterobacterEscherichiaHafniaMorganellaProvidenciaSerratia,Opportunisticdiseases-Enterobacteriaceae,.,6,Enterobacteriaceae:gastrointestinaldiseases,EscherichiacoliSalmonellaShigellaYersiniaentercolitica,.,7,Histocompatibilityantigen(HLA)B27EnterobacteriaceaeSalmonellaShigellaYersinia,NotEnterobacteriaceaeCampylobacterChlamydia,Reiterssyndrome,.,8,communityacquiredotherwisehealthypeopleKlebsiellapneumoniaerespiratorydiseasesprominentcapsuleurinarytractinfectionfecalcontaminationE.coliProteusurease(degradesurea)alkalineurine,Enterobacteriaceae,.,9,Enterobacteriaceae,gramnegativefacultativeanaerobicrodsoxidasenegative(nocytochromeoxidase),.,10,Emon,healthyintestineShigella,Salmonella,Yersinialactosenegativeidentified,Feces,.,11,othersitesidentifiedbiochemically,Enterobacteriaceae,.,12,Serotypes,referencelaboratoryantigensO(lipopolysaccharide)H(flagellar)K(capsular),.,13,Escherichiacoli,.,14,Escherichiacoli,Toxins:twotypesofenterotoxin;Shiga-typetoxin;EnteroaggregativeST-liketoxin;Hemolysins;EndotoxinTypeIIIsecretionsystemAdhesionscolonizationfactors;bothpiliorfimbriae;non-fimbrialfactorsinvolvedinattachment.Thereareatleast21differenttypesofadhesions.Virulencefactorsthatprotectthebacteriafromhostdefenses:Capsule/Ironcapturingability(enterochelin)Outermembraneproteins,.,15,E.colifimbriae,mannose,Type1,galactoseglycolipidsglycoproteins,P,.,16,E.coli-urinarytractinfectionIstheleadingcauseofurinarytractinfectionswhichcanleadtoacutecystitis(bladderinfection)andpyelonephritis(kidneyinfection).,.,17,E.coli-MeningitisandSepsis,Neonatalmeningitisistheleadingcauseofneonatalmeningitisandsepticemiawithahighmortalityrate.UsuallycausedbystrainswiththeK1capsularantigen.,.,18,EnteropathogenicE.coli,feverinfantdiarrheavomitingnauseanon-bloodystoolsDestructionofsurfacemicrovillilooseattachmentmediatedbybundleformingpili(Bfp);Stimulationofintracellularcalciumlevel;rearrangementofintracellularactin,.,19,EnterotoxigenicE.coli,Awaterydiarrhea,nausea,abdominalcrampsandlow-gradefeverfor1-5days.TravellersdiarrheaanddiarrheainchildrenindevelopingcountriesTransmissionisviacontaminatedfoodorwater.,.,20,EnterotoxigenicE.coli,diarrhealikecholeramildernurserytravellersdiarrheacausedbyLT,ST,orLT/ST.,.,21,EnterotoxigenicE.coli,HeatlabiletoxinlikecholeragenAdenylcyclaseactivatedcyclicAMPsecretionwater/ionsHeatstabletoxinGuanylatecyclaseactivatedcyclicGMPuptakewater/ions,.,22,LTvsSTactivity,.,23,E.coli-Enteroinvasive(EIEC),TheorganismattachestotheintestinalmucosaviapiliOutermembraneproteinsareinvolvedindirectpenetration,invasionoftheintestinalcells,anddestructionoftheintestinalmucosa.Thereislateralmovementoftheorganismfromonecelltoadjacentcells.Symptomsincludefever,severeabdominalcramps,malaise,andwaterydiarrheafollowedbyscantystoolscontainingblood,mucous,andpus.resemblesshigellosis,.,24,EnteroinvasiveE.coli(EIEC),Dysenteryresemblesshigellosiselderchildrenandadultdiarrhea,.,25,E.coli-c.Enteropathogenic(EPEC),Malaiseandlowgradefeverdiarrhea,vomiting,nausea,non-bloodystoolsBundleformingpiliareinvolvedinattachmenttotheintestinalmucosa.Thisleadstochangesinsignaltransductioninthecells,effacementofthemicrovilli,andtointimateattachmentviaanon-fimbrialadhesioncalledintimin.Thisisaproblemmainlyinhospitalizedinfantsandindaycarecenters.,.,26,.,27,E.coli-d.Enterohemorrhagic(EHEC),Hemorrhagicbloody,copiousdiarrheafewleukocytesafebrilehemolytic-uremicsyndromehemolyticanemiathrombocytopenia(lowplatelets)kidneyfailure,.,28,EnterohemorrhagicE.coli,UsuallyO157:H7,Transmissionelectronmicrograph,.,29,EnterohemorrhagicE.coli,Verotoxin“shiga-like”Hemolysinsyoungerthan5yearsold,causinghemorrhagiccolitis,.,30,EnteroaggregativeE.coli肠集聚型大肠杆菌,acauseofpersistent,waterydiarrheawithvomitinganddehydrationininfants.Thatisautoagglutinationinastackedbrickarrangement.thebacteriaadherestotheintestinalmucosaandelaboratesenterotoxins(enteroaggregativeheat-stabletoxin,EAST).Theresultismucosaldamage,secretionoflargeamountsofmucus,andasecretorydiarrhea.,.,31,E.coli-Enteroaggregative(EAggEC),Mucousassociatedautoagglutininscauseaggregationofthebacteriaatthecellsurfaceandresultintheformationofamucousbiofilm.Theorganismsattachviapiliandliberateacytotoxindistinctfrom,butsimilartotheSTandLTenterotoxinsliberatedbyETEC.Symptomsinclusewaterydiarrhea,vomiting,dehydrationandoccasionalabdominalpain.,.,32,VariousTypesofE.coli,.,33,SummaryofE.colistrainsthatcausegastroenteritis.,.,34,Sanitarysignificance,Totoalbacterialnumber:numberofbacteriacontainedpermlorgmofthesample;thestandardofdrinkingwaterislessthan100.Coliformbacteriaindex:thenumberofcoliformbacteriadetectedoutper1000mlsample;thestandardofdrinkingwaterislessthan3,.,35,Escherichiacoli,GeneticallyE.coliandShigellaaregeneticallyhighlycloselyrelated.Forpracticalreasons(primarilytoavoidconfusion)theyarenotplacedinthesamegenus.Notsurprisinglythereisalotofoverlapbetweendiseasescausedbythetwoorganisms.1)EnteropathogenicE.coli(EPEC).Certainserotypesarecommonlyfoundassociatedwithinfantdiarrhea.Theuseofgeneprobeshasconfirmedthesestrainsasdifferentfromothergroupslistedbelow.Thereisacharacteristicmorphologicallesionwithdestructionofmicrovilliwithoutinvasionoftheorganismthatsuggestsadhesionisimportant.Clinicallyoneobservesfever,diarrhea,vomitingandnauseausuallywithnon-bloodystools.2)EnterotoxigenicE.coli(ETEC)producediarrhearesemblingcholerabutmuchmilderindegree.Alsocausetravelersdiarrhea.Twotypesofplasmid-encodedtoxinsareproduced.a)Heatlabiletoxinswhicharesimilartocholeragen(seecholerasectionbelow).AdenylcyclaseisactivatedwithproductionofcyclicAMPandincreasedsecretionofwaterandions.b)Heatstabletoxins;guanylatecyclaseisactivatedwhichinhibitsionicandwateruptakefromthegutlumen.Waterydiarrhea,feverandnausearesultinbothcases.3)EnteroinvasiveE.coli(EIEC)producedysentery(indistinguishableclinicallyfromshigellosis,seebacillarydysenterybelow).4)EnterohemorrhagicE.coli(EHEC).TheseareusuallyserotypeO157:H7.Theseorganismscanproduceahemorrhagiccolitis(characterizedbybloodyandcopiousdiarrheawithfewleukocytesinafebrilepatients).Outbreaksareoftencausedbycontaminatedhamburgermeat.Theorganismscandisseminateintothebloodstreamproducingsystemichemolytic-uremicsyndrome(hemolyticanemia,thrombocytopeniaandkidneyfailure).ProductionofVerotoxin(biochemicallysimilartoshigatoxinthusalsoknownasshiga-like)ishighlyassociatedwiththisgroupoforganisms;encodedbyaphage.Hemolysins(plasmidencoded)arealsoimportantinpathogenesis.Asnotedabove,thereareatleast4etiologicallydistinctdiseases.However,inthediagnosticlaboratorygenerallythegroupsarenotdifferentiatedandtreatmentwouldbeonsymptomatology.Generallyfluidreplacementistheprimarytreatment.Antibioticsaregenerallynotusedexceptinseverediseaseordiseasethathasprogressedtoasystemicstage(e.g.hemolytic-uremiasyndrome).TwomajorclassesofpiliareproducedbyE.coli:mannosesensitiveandmannoseresistantpili.Theformerbindtomannosecontainingglyocoproteinsandthelattertocerebrosidesonthehostepitheliumallowingattachment.ThisaidsincolonizationbyE.coli.,.,36,Shigella,.,37,Shigella,S.flexneri,S.boydii,S.sonnei,S.dysenteriaebacillarydysenteryshigellosisbloodyfecesintestinalpainpus,.,38,Genralfeatures,Pili.Moststrainscannotfermentlactose;S.sonneicanslowly_fermentlactose.AccordingtoOantigen,4groupsEasilycausingdrug-resistence.,.,39,Shigellosis,within2-3daysepithelialcelldamage,.,40,Shigatoxin,enterotoxiccytotoxicinhibitsproteinsynthesislysing28SrRNA,.,41,Shigellaattachmentandpenetration,Within2-3daysEpithelialcelldamage,.,42,Clinicalsignificance,manonlyreservoirmostlyyoungchildrenfecaltooralcontactchildrentoadultstransmittedbyadultfoodhandlersunwashedhands,.,43,Clinicalsignificance,Theinfectivedoserequiredtocauseinfectionisverylow(10-200organisms).Thereisanincubationof1-7daysfollowedbyfever,cramping,abdominalpain,andwaterydiarrhea(duetothetoxin)for1-3days.Thismaybefollowedbyfrequent,scantstoolswithblood,mucous,andpus(duetoinvasionofintestinalmucosa).Isisrarefortheorganismtodisseminate.Theseverityofthediseasedependsuponthespeciesoneisinfectedwith.S.dysenteriaisthemostpathogenicfollowedbyS.flexneri,S.sonneiandS.boydii.,.,44,Immunity,SIgA.,.,45,DiagnosisofShigellainfection,Specimen:stool.CultureandIdentificationQuickimmunologicalmethods:Immunofluorescent“ball”test;Coagglutination.,.,46,Prevention,streptomycindependent(SD)dysenteryvaccine.,.,47,Treatingshigellosis,managedehydrationpatientsrespondtoantibiotics,Problemofdrug-resistancediseasedurationdiminished,.,48,Shigella,Shigella(4species;S.flexneri,S.boydii,S.sonnei,S.dysenteriae)allcausebacillarydysenteryorshigellosis,(bloodyfecesassociatedwithintestinalpain).Theorganisminvadestheepitheliallininglayer,butdoesnotpenetrate.Usually,within2-3days,dysenteryresultsfrombacteriadamagingtheepitheliumlininglayersoftheintestineoftenwithreleaseofmucusandblood(foundinthefeces)andattractionofleukocytes(alsofoundinthefecesaspus).Shigatoxin(chromosomallyencoded)isneurotoxic,enterotoxicandcytotoxicplaysarole.Thetoxininhibitsproteinsynthesis(actingonthe80Sribosomeandlysing28SrRNA).Thisisprimarilyadiseaseofyoungchildrenoccurringbyfecal-oralcontact.Adultscancatchthisdiseasefromchildren.Howeveritcanbetransmittedbyinfectedadultfoodhandlers,contaminatingfood.Thesourceineachcaseisunwashedhands.Manistheonlyreservoir.Patientswithseveredysenteryareusuallytreatedwithantibiotics(e.g.ampicillin).Incontrasttosalmonellosis,patientsrespondtoantibiotictherapyanddiseasedurationisdiminished.,.,49,Salmonella,Salmonellosismaypresentasoneofseveralsyndromesincludinggastroenteritis,enteric(typhoid)feverorsepticemia.,.,50,Theantigenicstructuresofsalmonellaeusedinserologictyping,.,51,Salmonella,2000antigenictypes”diseasecategoryS.enteritidismanyserotypesS.cholerae-suisS.typhi,.,52,Virulencefactors,EndotoxinmayplayaroleinintracellularsurvivalCapsule(forS.typhiandsomestrainsofS.paratyphi)Adhesionsbothfimbrialandnon-fimbrialTypeIIIsecretionsystemsandeffectormolecules2differentsystemsmaybefound:OnetypeisinvolvedinpromotingentryintointestinalepithelialcellsTheothertypeisinvolvedintheabilityofSalmonellatosurviveinsidemacrophagesOutermembraneproteins-involvedintheabilityofSalmonellatosurviveinsidemacrophagesFlagellahelpbacteriatomovethroughintestinalmucousEnterotoxin-maybeinvolvedingastroenteritisIroncapturingability,.,53,.,54,Entericortyphoidfever,Entericortyphoidfeveroccurswhenthebacterialeavetheintestineandmultiplywithincellsofthereticuloendothelialsystem.Thebacteriathenre-entertheintestine,causinggastrointestinalsymptoms.Typhoidfeverhasa10-14dayincubationperiodandmaylastforseveralweeks.Salmonellatyphiisthemostcommonspeciesisolatedfromthissalmonellosis.Humanreservoir:carrierstatecommonContaminatedfood:watersupplyPoorsanitaryconditions,.,55,Typhoid,acutephase,gastroenteritis,gallbladdershedding,weeks,Septicemia-occurs10-14dayslasts7days,gastrointenteritis,.,56,胆囊-肠道-粪排菌/肠壁淋巴组织肾-尿肝脾-肿大骨髓-受抑制皮肤-血栓出血-玫瑰疹,伤寒和付伤寒的致病过程,伤寒和付伤寒沙门菌,小肠上部粘膜,肠系膜淋巴结,固有层淋巴结,进入血液,再次进入血液,第一次菌血症,第二次菌血症,.,57,Typhoid-Therapy,AntibioticsessentialVaccinesVi(capsular)antigen:protective,.,58,Salmonellagastroenteritis,Salmonellagastroenteritisisthemostcommonformofsalmonellosisandgenerallyrequiresan8-48hourincubationperiodandmaylastfrom2-5days.Symptomsincludenausea,vomitinganddiarrhea(non-bloodystool).Salmonellaenteritidisisthemostcommonisolate.poultry家禽,eggs.nohumanreservoirself-limiting(2-5days),.,59,Salmonellasepticemia,Salmonellasepticemia(bacteremia)maybecausedbyanyspeciesbutS.cholerae-suisiscommon.ThisdiseaseresemblesotherGram-negativesepticemiasandischaracterizedbyahigh,remittentfeverwithlittlegastrointestinalinvolvement.,.,60,Immunity(S.typhi),Vi(capsular)antigenprotective,.,61,Diagnosis,A.Specimensa)Entericfever:blood,bonemarrow,stool,urine.b)Foodpoisoning:stool,vomitus,suspectedfood.c)Septicemia:blood.B.CultureandidentificationC.Widaltest,.,62,.,63,Salmonella,Usingappropriateantibodiesmorethan2000antigenic“types”havebeenrecognized.Thereare,however,onlyafewtypesthatarecommonlyassociatedwithcharacteristichumandiseases(mostsimplyreferredtoasS.enteritidis,S.cholerae-suisandS.typhi).Salmonellosis,thecommonsalmonellainfection,iscausedbyavarietyofserotypes(S.enteritidis)andistransmittedfromcontaminatedfood(suchaspoultryandeggs).Itdoesnothaveahumanreservoirandusuallypresentsasgastroenteritis(nausea,vomitingandnon-bloodystools).Thediseaseisusuallyself-limiting(2-5days).LikeShigellatheyinvadetheepitheliumanddonotproducesystemicinfection.Inuncomplicatedcasesofsalmonellosis,whicharethevastmajority,antibiotictherapyisnotuseful.S.cholerae-suis(seenmuchlesscommonly)causessepticemiaafterinvasion.Inthiscase,antibiotictherapyisrequired.Theseverestformofsalmonellainfectionstyphoid(entericfever),causedbySalmonellatyphi.Althoughitisoneofthehistoricalcausesofwidespreadepidemicsandstillisinthethirdworld.Theorganismistransmittedfromahumanreservoirorinthewatersupp