RNAi Screen in Drosophila Cells Reveals the Involvement of the Tom Complex in Chlamydia Infection 英文参考文献.docVIP

RNAiScreeninDrosophilaCellsReveals theInvolvementoftheTomComplex inChlamydiaInfection Isabelle Derre′1*,Marc Pypaert2,3,Alice Dautry-Varsat4,5,Herve′ Agaisse1 1SectionofMicrobialPathogenesis,YaleUniversitySchoolofMedicine,NewHavenConnecticut,UnitedStatesofAmerica,2DepartmentofCellBiology,YaleUniversity School of Medicine, New Haven, Connecticut, United States of America, 3 Center for Cell and Molecular Imaging, Yale University School of Medicine, New Haven, Connecticut,UnitedStatesofAmerica,4Unite′ deBiologiedesInteractionsCellulaires,InstitutPasteur,Paris,France,5CNRSURA2582,Paris,France Chlamydiaspp.areintracellularobligatebacterialpathogensthatinfectawiderangeofhostcells.Here,weshowthat C. caviae enters, replicates, and performs a complete developmental cycle in Drosophila SL2 cells. Using this model system, we have performed a genome-wide RNA interference screen and identified 54 factors that, when depleted, inhibitC.caviaeinfection.Bytestingtheeffectofeachcandidate’sknockdownonL.monocytogenesinfection,wehave identified 31 candidates presumably specific of C. caviae infection. We found factors expected to have an effect on Chlamydia infection, such as heparansulfate glycosaminoglycans and actin and microtubule remodeling factors. We also identified factors that were not previously described as involved in Chlamydia infection. For instance, we identified members of the Tim-Tom complex, a multiprotein complex involved in the recognition and import of nuclear-encoded proteins to the mitochondria, as required for C. caviae infection of Drosophila cells. Finally, we confirmedthatdepletionofeitherTom40orTom22alsoreducedC.caviaeinfectioninmammaliancells.However,C. trachomatisinfectionwasnotaffected,suggestingthatthemechanisminvolvedisC.caviaespecific. Citation:Derre′ I,PypaertM,Dautry-VarsatA,AgaisseH(2007)RNAiscreeninDrosophilacellsrevealstheinvolvementoftheTomcomplexinChlamydiainfection.PLoS Pathog3(10):e155.doi:10.1371/journal.ppat.0030155 lysed, leading to th