Effect of Rickettsial Toxin VapC on Its Eukaryotic Host 英文参考文献.docVIP

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Effect of Rickettsial Toxin VapC on Its Eukaryotic Host 英文参考文献.doc

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Effect of Rickettsial Toxin VapC on Its Eukaryotic Host 英文参考文献

EffectofRickettsialToxinVapConItsEukaryoticHost GillesAudoly1,RenaudVincentelli2,SophieEdouard1,KalliopiGeorgiades1,OlegMediannikov1, Gre′goryGimenez1,CristinaSocolovschi1,Jean-LouisMe`ge1,ChristianCambillau2,DidierRaoult1* 1Unite′ desRickettsiesURMITE,UMRCNRS6236-IRD198,Marseille,France,2AFMB,CNRSUMR6098,Marseille,France Abstract Rickettsia are intracellular bacteria typically associated with arthropods that can be transmitted to humans by infected vectors.Rickettsiaspp.cancausemildtoseverehumandiseasewithapossibleprotectioneffectofcorticosteroidswhen antibiotictreatmentsareinitiated.Weidentifiedlaterallytransferredtoxin-antitoxin(TA)geneticelements,includingvapB/C, in several Rickettsia genomesand showed that theyare functional in bacteria and eukaryotic cells. We also generated a plaqueassaytomonitortheformationoflyticplaquesovertimeanddemonstratedthatchloramphenicolaccelerateshost celllysisofvapB/C-containingRickettsia.Whole-genomeexpression,TUNELandFISHassaysontheinfectedcellsfollowing exposuretotheantibioticrevealedearlyapoptosisofhostcells,whichwaslinkedtoover-transcriptionofbacterialvapB/C operons and subsequent cytoplasmic VapC toxin release. VapC that is expressed in Escherichia coli and Saccharomyces cerevisiaeormicroinjectedintomammaliancellsistoxicthroughRNaseactivityandispreventedbydexamethasone.This studyprovidesthefirstbiologicalevidencethattoxin–antitoxinelementsactaspathogenicfactorsinbacterialhostcells, confirmingcomparativegenomicevidenceoftheirroleinbacterialpathogenicity.Ourresultssuggestthatearlymortality followingantibiotictreatmentofsomebacterialinfectionscanbepreventedbyadministrationofdexamethasone. Citation:AudolyG,VincentelliR,EdouardS,GeorgiadesK,MediannikovO,etal.(2011)EffectofRickettsialToxinVapConItsEukaryoticHost.PLoSONE6(10): e26528.doi:10.1371/journal.pone.0026528 Editor:KirstenNielsen,UniversityofMinnesota,UnitedStatesofAmerica ReceivedJune8,2011;AcceptedSeptember28,2011;PublishedOctober27,2011 Copyright: ? 2011 Audoly et al.