Differential Infectivity by the Oral Route of Trypanosoma cruzi Lineages Derived from Y Strain 英文参考文献.docVIP

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Differential Infectivity by the Oral Route of Trypanosoma cruzi Lineages Derived from Y Strain 英文参考文献.doc

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Differential Infectivity by the Oral Route of Trypanosoma cruzi Lineages Derived from Y Strain 英文参考文献

DifferentialInfectivitybytheOralRouteofTrypanosoma cruziLineagesDerivedfromYStrain CristianCortez1,RafaelM.Martins1,2,RenanM.Alves1,RichardC.Silva1,LucianaC.Bilches1, SileneMacedo1,VanessaD.Atayde1,3,SilviaY.Kawashita1,4,MarceloR.S.Briones1,NobukoYoshida1* 1DepartamentodeMicrobiologia,ImunologiaeParasitologia,UniversidadeFederaldeSa?o Paulo,Sa?o Paulo,Brazil,2Unite′ deBiologiedesInteractionsHo?te-Parasite, InstitutPasteur,Paris,France,3McGillUniversityHealthCentre,Montre′al,Quebec,Canada,4Superintende?nciadaPol?′ciaTe′cnico-Cient?′fica,Sa?o Paulo,Brazil Abstract Background:DiversityofT.cruzistrainsisacentralprobleminChagasdiseaseresearchbecauseofitscorrelationwiththe wide range of clinical manifestations and the biogeographical parasite distribution. The role played by parasite microdiversityinChagasdiseaseepidemiologyisstilldebatable.Alsoawaitsclarificationwhethersuchdiversityisassociated withtheoutcomeoforalT.cruziinfection,responsibleforfrequentoutbreaksofacuteChagasdisease. MethodsandFindings:WeaddressedtheimpactofmicrodiversityinoralT.cruziinfection,bycomparativeanalysisoftwo strains,Y30andY82,bothderivedfromYstrain,awidelyusedexperimentalmodel.Networkgenealogiesoffournuclear genes(SSUrDNA,actin,DHFR-TS,EF1a)revealedthatY30iscloselyrelatedtoDiscreteTypingUnitTcIIwhileY82ismore closelyrelatedtoTcVI,agroupcontaininghybridstrains.Nevertheless,exceptingoneA-Gtransitionatposition1463,Y30 andY82SSUrDNAswereidentical.Y82strain,expressingthesurfacemoleculegp82,infectedmiceorallymoreefficiently thanY30,whichexpressesarelatedgp30molecule.Bothmoleculesareinvolvedinlysosomeexocytosis-dependenthost cell invasion, but exhibit differential gastric mucin-binding capacity, a property critical for parasite migration toward the gastric mucosal epithelium. Upon oral infection of mice, the number of Y30 and Y82 parasites in gastric epithelial cells differedwidely. Conclusions:Weconcludethatmetacyclicformsofgp82-expressingY82strain,closelyrelatedtoTcVI,arebetterada