Proteomic Analysis of Human Skin Treated with Larval Schistosome Peptidases Reveals Distinct Invasion Strategies among Species of Blood Flukes 英文参考文献.docVIP

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Proteomic Analysis of Human Skin Treated with Larval Schistosome Peptidases Reveals Distinct Invasion Strategies among Species of Blood Flukes 英文参考文献.doc

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ProteomicAnalysisofHumanSkinTreatedwithLarval SchistosomePeptidasesRevealsDistinctInvasion StrategiesamongSpeciesofBloodFlukes JessicaIngram1,GiselleKnudsen2,3,K.C.Lim3,ElizabethHansell3,JudySakanari3,JamesMcKerrow3* 1Tetrad Graduate Program, University of California San Francisco, San Francisco, California, United States of America, 2Mass Spectrometry Facility, Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, United States of America, 3Sandler Center for Drug Discovery, California InstituteforQuantitativeBiosciences(QB3),UniversityofCaliforniaSanFrancisco,SanFrancisco,California,UnitedStatesofAmerica Abstract Background:Skininvasionistheinitialstepininfectionofthehumanhostbyschistosomebloodflukes.Schistosomelarvae have the remarkable ability to overcome the physical and biochemical barriers present in skin in the absence of any mechanicaltrauma.Whileaserinepeptidasewithactivityagainstinsolubleelastinappearstobeessentialforthisprocessin one species of schistosomes, Schistosoma mansoni, it is unknown whether other schistosome species use the same peptidasetofacilitateentryintotheirhosts. Methods: Recent genome sequencing projects, together with a number of biochemical studies, identified alternative peptidasesthatSchistosomajaponicumorTrichobilharziaregenticouldusetofacilitatemigrationthroughskin.Inthisstudy, we used comparative proteomic analysis of human skin treated with purified cercarial elastase, the known invasive peptidaseofS.mansoni,orS.mansonicathespinB2,aclosehomologoftheputativeinvasivepeptidaseofS.japonicum ,to identifysubstratesofeitherpeptidase.Selectskinproteinswerethenconfirmedassubstratesbyinvitrodigestionassays. Conclusions:ThisstudydemonstratesthatanS.mansoniorthologofthecandidateinvasivepeptidaseofS.japonicumand T. regenti, cathepsin B2, is capable of efficiently cleaving many of the same host skin substrates as the invasive serine peptidaseofS.mansoni,cercarialelastase.Atthesametime,ide