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EvolutionandEcologyofPathogensMartinPolzCivil&EnvironmentalEngineeringMassachusettsInstituteofTechnologyEvolutionandEcologyofPatho1OutlineEmergenceofpathogensGlobalimportanceofmicroorganismsWhatarepathogens?EvolutionofpathogenesisRe-emergenceofpathogensAntibioticresistanceCholeraConclusionsOutlineEmergenceofpathogens2Germs,germseverywhereEvenonalittlepear,Germsgermsallaround,Evenonthedirtyground.Germs,germsmakemesick,Especiallyonacandystick.Germs,germsaresosmall,Evenonabouncyball.Candice'sGermPoemGerms,germseverywhereCandic3Microbialcommunitiesdrivebiogeochemicalcycles…Microbialcommunitiesdrivebi4100humanactivities140biologicalfixation200denitrificationSOILATMOSPHEREOCEANS15biologicalfixation140denitrification1200internalcycling8000internalcycling10burial36riverflow<3fixationinlighteninggroundwaterExample:TheNitrogenCycle100140200SOILATMOSPHEREOCEANS15?humanactivities140biologicalfixation200denitrificationSOILATMOSPHEREOCEANS15biologicalfixation140denitrification1200internalcycling8000internalcycling?burial?riverflow<3fixationinlighteninggroundwaterNitrogenCycleWithoutMicrobesAllprocessesslow.Wouldlifebepossible??140200SOILATMOSPHEREOCEANS1516MicrobesBacteriaFungiProtistsVirusesMicrobesBacteria7BacteriaSmallEfficientBiochemicallydiverseFastgrowthBacteriaSmall8MarineFreshwaterSedimentsSubsurfacesediments (0-3,000m)AnimalgutsCells/mlorgx106Totalcellsx10260.51.04,6000.34-2001-1051,0001.517038,0000.0004(Whitmanetal.1998)BacteriaareeverywhereMarineFreshwaterSedimentsSubsu9Globalbacterialbiomass(PgofC)SoilandAquaticPlantsBacteriaSubsurfaceTerrestrialMarine5601.8262.222-215303MicrobialbiomassrivalsplantbiomassbuthashigherturnoverGlobalbacterialbiomass(Pgo10Howmanybacterial

speciesarethere?Wilson1988Totalnumberspecies:~1.4millionBacteria:~3,500Hammond1995Totalnumberspecies:~11millionBacteria:~10millionHowmanybacterial

speciesare11ThegreatplatecountanomalymicrobialcommunityplatingDAPIstainedmarinewatersample<1%ofobservablebacteriagrowonstandardculturemediaThegreatplatecountanomalym12GeneticdiversityTotalnucleicacids16SribosomalRNAgenesSequencesDiversityandevolutionaryrelationshipsIdentificationandquantificationGeneticdiversityTotalnucleic13抗生素英文課件——Evolution-and-Ecology-of-Pathogens14Molecularapproach:greatdiversityofmicrobespathogensonlyaminorcomponent ofmicrobialdiversityallowsunderstandingofevolution ofpathogenesisMolecularapproach:15EmergenceofpathogensEmergenceofpathogens16Whatisapathogen?Anevolutionaryview.Example:Escherichiacoli(E.coli)Normallyaharmlessgutbacteriumbut…EterotoxigenicstrainsEnteropathogenicstrainsEnteroinvasivestrainsEnterohemorrhagicstrainsEnteroaggregativestrainsUropathogenicstrainsWhatisapathogen?Example:Es17GenomeanalysisprovidesanswerStrainscloselyrelatedGenomestructuresimilarBut….Insertionsof‘foreign’DNA=pathogenicityislandsComparativeanalysis:Genomeanalysisprovidesanswe18ComparisonharmlessandpathogenicE.colistrainsABABCCE.coliK12E.coliO157:H7ForeignDNA=locusofenterocyteeffacementResponsibleforpathogenicity:allowsattachmentandtoxinproductionsAharmlessbacteriumhasbecomeapathogenby‘stealing’DNAfromanotherbacterium!ComparisonharmlessandABABCCE19Mechanismsofgenetransfer:Transformation:uptakeofDNAfromenvironmentTransduction:DNAtransferbyvirusesConjugation:plasmidtransferbetweenbacterialcells123CanalltransfergenesfromotherbacteriathatcanbecomeincorporatedintogenomeMechanismsofgenetransfer:Tr20Fateoftransferredgenes:RecAsystem=recombinationintogenomedependentonsequencesimilarity%sequencedifferencerecombinationrateFateoftransferredgenes:RecA21Howoftendoesgenetransferhappen?Genetransferisraree.g.,transductionbyvirusesinsertforeignDNAevery108virusinfectionsBut….Microbeshaveverylargepopulationse.g.,genetransferinmarineenvironment~20millionbilliontimespersecond!Genesmustbeadvantageoustorecipient….Howoftendoesgenetransferh22EcologyofpathogenesisBacteriagrowfastHighpopulationdensitiesGreatcompetitionforresourcesPathogen=normalbacteriumthathasgainedaccesstoanewresourcethroughnewgenes-->CompetitiveadvantageEcologyofpathogenesisBacteri23Re-emergenceofpathogensRe-emergenceofpathogens24Example1:AntibioticsAntibiotics-naturalwarfarecommonresourcespecies1species2Example1:AntibioticsAntibiot25Example1:AntibioticsAntibiotics-naturalwarfarecommonresourcespecies1species2antibioticExample1:AntibioticsAntibiot26Example1:AntibioticsAntibiotics-naturalwarfarecommonresourcespecies1species2antibioticExample1:AntibioticsAntibiot27Example1:AntibioticsAntibiotics-naturalwarfarecommonresourcespecies1Example1:AntibioticsAntibiot28AntibioticresistanceBacteriahaveevolvedresistancegenestoantibioticsLocatedonplasmidsAntibioticresistanceBacteria29PlasmidencodedresistanceiseasilytransferredbetweenspeciesbecauseplasmidsaremobileOccurrenceusuallylowunlessselectionthroughwidespreadantibioticusePlasmidencodedresistanceis30Antibioticsoverusecreates‘Superbugs’50milliontonsantibioticsperyear‘Superbugs’resistanttomostantibioticsExample:Tuberculosis2.5milliondeathsMycobacteriumtuberculosisincreasinglyresistantAntibioticsoverusecreates‘S31Example2:CholeraandclimateVibriocholeraeandothervibriosubiquitousinmarine,coastalwatersGeneticallysimilarnon-pathogenicandpathogenicstrainsco-existV.choleraExample2:Choleraandclimate32Vibriospeciesidentifiedas

agentsofhumandisease

Vibriospeciesidentifiedas

33SeasonalcholerainCalcutta(Sharma,1998)SeasonalcholerainCalcutta(S34Vibrioinfections

linkedtoElNino

Dhaka,BangladeshCholeracases

SeasonalityRemoved

(Pascual,2000)Vibrioinfections

linkedtoE35Attachmenttoalgaeandzooplankton?Temperaturedependentgrowth?PossiblereasonsforseasonalityAlgalgrowth=vibriogrowth?TTemperaturerise=vibriogrowth?Linkstoglobalwarmingand/orpollutionAttachmenttoalgaeandzoopla36ConclusionsConclusions37Re-Emergenceisanevolutionary/ecologicalphenomenonMicrobialcommunitiesextremelydiverseLargenumbersofindividualsPotentialforgenetransferPathogenesisarisesviagenetransferResult:harmlessbacterialspeciesbecomespathogenbecauseitgainscompetitiveadvantageEcologicalfactors(resistance,alternatehosts,climate)maytriggerincreasedincidenceofpathogenesisRe-Emergenceisanevolutionar38OutlookforthefutureNeedtounderstandenvironmental

contextofpathogenesisNeedtounderstandgenetransferratesanddiversityofco-occurringgenomesOutlookforthefuture39Thanksto:SilviaAcinasDanDistelDanaHuntVanjaKlepacLuisaMarcelinoChanathipPharinoRamahiSarma-RupavtarmJanelleThompsonNSF,NIH,Seagrant,DOE-GenomestoLifeThanksto:SilviaAcinasNSF,NI40EvolutionandEcologyofPathogensMartinPolzCivil&EnvironmentalEngineeringMassachusettsInstituteofTechnologyEvolutionandEcologyofPatho41OutlineEmergenceofpathogensGlobalimportanceofmicroorganismsWhatarepathogens?EvolutionofpathogenesisRe-emergenceofpathogensAntibioticresistanceCholeraConclusionsOutlineEmergenceofpathogens42Germs,germseverywhereEvenonalittlepear,Germsgermsallaround,Evenonthedirtyground.Germs,germsmakemesick,Especiallyonacandystick.Germs,germsaresosmall,Evenonabouncyball.Candice'sGermPoemGerms,germseverywhereCandic43Microbialcommunitiesdrivebiogeochemicalcycles…Microbialcommunitiesdrivebi44100humanactivities140biologicalfixation200denitrificationSOILATMOSPHEREOCEANS15biologicalfixation140denitrification1200internalcycling8000internalcycling10burial36riverflow<3fixationinlighteninggroundwaterExample:TheNitrogenCycle100140200SOILATMOSPHEREOCEANS145?humanactivities140biologicalfixation200denitrificationSOILATMOSPHEREOCEANS15biologicalfixation140denitrification1200internalcycling8000internalcycling?burial?riverflow<3fixationinlighteninggroundwaterNitrogenCycleWithoutMicrobesAllprocessesslow.Wouldlifebepossible??140200SOILATMOSPHEREOCEANS15146MicrobesBacteriaFungiProtistsVirusesMicrobesBacteria47BacteriaSmallEfficientBiochemicallydiverseFastgrowthBacteriaSmall48MarineFreshwaterSedimentsSubsurfacesediments (0-3,000m)AnimalgutsCells/mlorgx106Totalcellsx10260.51.04,6000.34-2001-1051,0001.517038,0000.0004(Whitmanetal.1998)BacteriaareeverywhereMarineFreshwaterSedimentsSubsu49Globalbacterialbiomass(PgofC)SoilandAquaticPlantsBacteriaSubsurfaceTerrestrialMarine5601.8262.222-215303MicrobialbiomassrivalsplantbiomassbuthashigherturnoverGlobalbacterialbiomass(Pgo50Howmanybacterial

speciesarethere?Wilson1988Totalnumberspecies:~1.4millionBacteria:~3,500Hammond1995Totalnumberspecies:~11millionBacteria:~10millionHowmanybacterial

speciesare51ThegreatplatecountanomalymicrobialcommunityplatingDAPIstainedmarinewatersample<1%ofobservablebacteriagrowonstandardculturemediaThegreatplatecountanomalym52GeneticdiversityTotalnucleicacids16SribosomalRNAgenesSequencesDiversityandevolutionaryrelationshipsIdentificationandquantificationGeneticdiversityTotalnucleic53抗生素英文課件——Evolution-and-Ecology-of-Pathogens54Molecularapproach:greatdiversityofmicrobespathogensonlyaminorcomponent ofmicrobialdiversityallowsunderstandingofevolution ofpathogenesisMolecularapproach:55EmergenceofpathogensEmergenceofpathogens56Whatisapathogen?Anevolutionaryview.Example:Escherichiacoli(E.coli)Normallyaharmlessgutbacteriumbut…EterotoxigenicstrainsEnteropathogenicstrainsEnteroinvasivestrainsEnterohemorrhagicstrainsEnteroaggregativestrainsUropathogenicstrainsWhatisapathogen?Example:Es57GenomeanalysisprovidesanswerStrainscloselyrelatedGenomestructuresimilarBut….Insertionsof‘foreign’DNA=pathogenicityislandsComparativeanalysis:Genomeanalysisprovidesanswe58ComparisonharmlessandpathogenicE.colistrainsABABCCE.coliK12E.coliO157:H7ForeignDNA=locusofenterocyteeffacementResponsibleforpathogenicity:allowsattachmentandtoxinproductionsAharmlessbacteriumhasbecomeapathogenby‘stealing’DNAfromanotherbacterium!ComparisonharmlessandABABCCE59Mechanismsofgenetransfer:Transformation:uptakeofDNAfromenvironmentTransduction:DNAtransferbyvirusesConjugation:plasmidtransferbetweenbacterialcells123CanalltransfergenesfromotherbacteriathatcanbecomeincorporatedintogenomeMechanismsofgenetransfer:Tr60Fateoftransferredgenes:RecAsystem=recombinationintogenomedependentonsequencesimilarity%sequencedifferencerecombinationrateFateoftransferredgenes:RecA61Howoftendoesgenetransferhappen?Genetransferisraree.g.,transductionbyvirusesinsertforeignDNAevery108virusinfectionsBut….Microbeshaveverylargepopulationse.g.,genetransferinmarineenvironment~20millionbilliontimespersecond!Genesmustbeadvantageoustorecipient….Howoftendoesgenetransferh62EcologyofpathogenesisBacteriagrowfastHighpopulationdensitiesGreatcompetitionforresourcesPathogen=normalbacteriumthathasgainedaccesstoanewresourcethroughnewgenes-->CompetitiveadvantageEcologyofpathogenesisBacteri63Re-emergenceofpathogensRe-emergenceofpathogens64Example1:AntibioticsAntibiotics-naturalwarfarecommonresourcespecies1species2Example1:AntibioticsAntibiot65Example1:AntibioticsAntibiotics-naturalwarfarecommonresourcespecies1species2antibioticExample1:AntibioticsAntibiot66Example1:AntibioticsAntibiotics-naturalwarfarecommonresourcespecies1species2antibioticExample1:AntibioticsAntibiot67Example1:AntibioticsAntibiotics-naturalwarfarecommonresourcespecies1Example1:AntibioticsAntibiot68AntibioticresistanceBacteriahaveevolvedresistancegenestoantibioticsLocatedonplasmidsAntibioticresistanceBacteria69PlasmidencodedresistanceiseasilytransferredbetweenspeciesbecauseplasmidsaremobileOccurrenceusuallylowunlessselectionthroughwidespreadantibioticusePlasmidencodedresistanceis70Antibioticsoverusecreates‘Superbugs’50milliontonsantibioticsperyear‘Superbugs’resistanttomostantibioticsExample:Tuberculosis2.5milliondeathsMycobacteriumtuberculosisincreasinglyresistantAntibioticsoverusecreates‘S71Example2:CholeraandclimateVibriocholeraeandothervibriosubiquitousinmarine,coastalwatersGeneticallysim

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