Polyphosphate Kinase 2 A Novel Determinant of Stress Responses and Pathogenesis in Campylobacter jejuni 英文参考文献.docVIP

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Polyphosphate Kinase 2 A Novel Determinant of Stress Responses and Pathogenesis in Campylobacter jejuni 英文参考文献.doc

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Polyphosphate Kinase 2 A Novel Determinant of Stress Responses and Pathogenesis in Campylobacter jejuni 英文参考文献

PolyphosphateKinase2:ANovelDeterminantofStress ResponsesandPathogenesisinCampylobacterjejuni DharaneshGangaiah1,ZheLiu1,Jesu′sArcos2,IssmatI.Kassem1,YasserSanad1,JordiB.Torrelles2, GireeshRajashekara1* 1Food Animal Health Research Program, Ohio Agricultural Research Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster,Ohio,UnitedStatesofAmerica,2CenterforMicrobialInterfaceBiology,TheOhioStateUniversity,Columbus,Ohio,UnitedStatesofAmerica Abstract Background:Inorganicpolyphosphate(polyP)playsanimportantroleinstresstoleranceandvirulenceinmanybacteria. PPK1istheprincipalenzymeinvolvedinpolyPsynthesis,whilePPK2usespolyPtogenerateGTP,asignalingmoleculethat serves as an alternative energy source and a precursor for various physiological processes. Campylobacter jejuni , an important cause of foodborne gastroenteritis in humans, possesses homologs of both ppk1 and ppk2. ppk1 has been previouslyshowntoimpactthepathobiologyofC.jejuni. Methodology/PrincipalFindings:Here,wedemonstrateforthefirsttimethatthedeletionofppk2inC.jejuniresultedina significantdecreaseinpolyP-dependentGTPsynthesis,whiledisplayinganincreasedintracellularATP:GTPratio.TheDppk2 mutantexhibitedasignificantsurvivaldefectunderosmotic,nutrient,aerobic,andantimicrobialstressesanddisplayedan enhanced ability to form static biofilms. However, the Dppk2 mutant was not defective in poly P and ppGpp synthesis suggestingthatPPK2-mediatedstresstoleranceisnotppGpp-mediated.Importantly,theDppk2mutantwassignificantly attenuatedininvasionandintracellularsurvivalwithinhumanintestinalepithelialcellsaswellasinchickencolonization. Conclusions/Significance:Takentogether,wehavehighlightedtheroleofPPK2asanovelpathogenicitydeterminantthat iscriticalforC.jejunisurvival,adaptation,andpersistenceinthehostenvironments.PPK2isabsentinhumansandanimals; therefore,canserveasanoveltargetfortherapeuticinterventionofC.jejuniinfections. Citation:GangaiahD,LiuZ,ArcosJ,KassemII,SanadY,etal.(2010