Nasopharyngeal Colonization and Invasive Disease Are Enhanced by the Cell Wall Hydrolases LytB and LytC of Streptococcus pneumoniae 英文参考文献.docVIP

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Nasopharyngeal Colonization and Invasive Disease Are Enhanced by the Cell Wall Hydrolases LytB and LytC of Streptococcus pneumoniae 英文参考文献.doc

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Nasopharyngeal Colonization and Invasive Disease Are Enhanced by the Cell Wall Hydrolases LytB and LytC of Streptococcus pneumoniae 英文参考文献

NasopharyngealColonizationandInvasiveDiseaseAre EnhancedbytheCellWallHydrolasesLytBandLytCof Streptococcuspneumoniae ElisaRamos-Sevillano,MiriamMoscoso,PedroGarc?′a,ErnestoGarc?′a,JoseYuste*¤ CentrodeInvestigacionesBiolo′gicas,ConsejoSuperiordeInvestigacionesCient?′ficas,andCIBERdeEnfermedadesRespiratorias(CIBERES),Madrid,Spain Abstract Background:Streptococcuspneumoniaeisacommoncolonizerofthehumannasopharynxandoneofthemajorpathogens causing invasive disease worldwide. Dissection of the molecular pathways responsible for colonization, invasion, and evasionoftheimmunesystemwillprovidenewtargetsforantimicrobialorvaccinetherapiesforthiscommonpathogen. Methodology/PrincipalFindings:Wehaveconstructedmutantslackingthepneumococcalcellwallhydrolases(CWHs)LytB andLytCtoinvestigatetheroleoftheseproteinsindifferentphasesofthepneumococcalpathogenesis.Ourresultsshow thatLytBandLytCareinvolvedintheattachmentofS.pneumoniaetohumannasopharyngealcellsbothinvitroandinvivo. The interaction of both proteins with phagocytic cells demonstrated that LytB and LytC act in concert avoiding pneumococcal phagocytosis mediated by neutrophils and alveolar macrophages. Furthermore, C3b deposition was increasedonthelytCmutantconfirmingthatLytCisinvolvedincomplementevasion.Asaresult,thelytCmutantshoweda reducedabilitytosuccessfullycausepneumococcalpneumoniaandsepsis.BacterialmutantslackingbothLytBandLytC showedadramaticallyimpairedattachmenttonasopharyngealcellsaswellasamarkeddegreeofattenuationinamouse modelofcolonization.Inaddition,C3bdepositionandphagocytosiswasmoreefficientforthedoublelytBlytCmutantand itsvirulencewasgreatlyimpairedinbothsystemicandpulmonarymodelsofinfection. Conclusions/Significance:ThisstudyconfirmsthattheCWHsLytBandLytCofS.pneumoniaeareessentialvirulencefactors involvedinthecolonizationofthenasopharynxandintheprogressofinvasivediseasebyavoidinghostimmunity. Citation: Ramos-SevillanoE,MoscosoM,Garc?′aP,Garc?′aE,YusteJ(2011) Nasopharyngeal ColonizationandInvasiveDisease