Rickettsia conorii Transcriptional Response within Inoculation Eschar 英文参考文献.docVIP

RickettsiaconoriiTranscriptionalResponsewithin InoculationEschar PatriciaRenesto1*,ClarisseRovery1,JacquesSchrenzel2,QuentinLeroy1,AntoineHuyghe2,WenjunLi1, HubertLepidi1,PatriceFranc?ois2,DidierRaoult1 1Unite′ desRickettsies,IRD-CNRSUMR6236,Faculte′ deMe′decine,Marseille,France,2ServiceofInfectiousDiseases/GenomicResearchLaboratory,UniversityofGeneva Hospitals,Geneva,Switzerland Abstract Background:Rickettsiaconorii,thecausativeagentoftheMediterraneanspottedfever,istransmittedtohumansbythebite ofinfectedticksRhipicephalussanguineus.TheskinthusconstitutesanimportantbarrierfortheentryandpropagationofR. conorii. Given this, analysis of the survival strategies used by the bacterium within infected skin is critical for our understandingofrickettsiosis. Methodology/Principal Findings: Here, we report the first genome-wide analysis of R. conorii gene expression from infectedhumanskinbiopsies.OurdatashowedthatR.conoriiexhibitedastrikingtranscriptsignaturethatisremarkably conservedacrosspatients,regardlessofgenotype.TheexpressionprofilesobtainedusingcustomAgilentmicroarrayswere validatedbyquantitativeRT-PCR.Withineschars,theamountofdetectedR.conoriitranscriptswasof55%,thisvaluebeing of74%forbacteriagrowninVerocells.Insuchinfectedhosttissues,approximately15%(n=211)ofthetotalpredictedR. conoriiORFsappeareddifferentiallyexpressedcomparedtobacteriagrowninstandardlaboratoryconditions.Thesegenes are mostly down-regulated and encode proteins essential for bacterial replication. Some of the strategies displayed by rickettsiaetoovercomethehostdefensebarriers,thusavoidingkilling,werealsopointedout.Theobservedup-regulation of rickettsial genes associated with DNA repair is likely to correspond to a DNA-damaging agent enriched environment generated by the host cells to eradicate the pathogens. Survival of R. conorii within eschars also involves adaptation to osmotic stress, changes in cell surface proteins and up-regulation of some virulence factors. Interestingly, in contrast to d