A Novel Metal Transporter Mediating Manganese Export (MntX) Regulates the Mn to Fe Intracellular Ratio and Neisseria meningitidis Virulence 英文参考文献.docVIP

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A Novel Metal Transporter Mediating Manganese Export (MntX) Regulates the Mn to Fe Intracellular Ratio and Neisseria meningitidis Virulence 英文参考文献.doc

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A Novel Metal Transporter Mediating Manganese Export (MntX) Regulates the Mn to Fe Intracellular Ratio and Neisseria meningitidis Virulence 英文参考文献

ANovelMetalTransporterMediatingManganeseExport (MntX)RegulatestheMntoFeIntracellularRatioand NeisseriameningitidisVirulence Fre′de′ricJ.Veyrier1,2,3,4*,IvoG.Boneca2,3,MathieuF.Cellier4,Muhamed-KheirTaha1 1InstitutPasteur,InfectionBacte′riennesInvasives,Dept.InfectionetEpide′miologie,Paris,France,2InstitutPasteur,GroupeBiologieetge′ne′tiquedelaparoibacte′rienne, Dept.Microbiologie,Paris,France,3INSERM,GroupeAvenir,Paris,France,4INRS-InstitutArmand-Frappier,Laval,Quebec,Canada Abstract Neisseriameningitidis(Nm)andN.gonorrhoeae(Ng)areadaptedtodifferentenvironmentswithintheirhumanhost.Ifthe basisofthisdifferencehasnotyetbeenfullyunderstood,previousstudies(includingourowndata)havereportedthat, unlikeNg,Nmtolerateshighmanganeseconcentrations. Astransitionmetalsareessentialregulatorsofcellgrowthand host pathogen interactions, we aimed to address mechanisms of Nm Mn2+ tolerance and its pathogenic consequences. Usingbioinformatics,genedeletionandheterologousexpressionweidentifiedaconservedbacterialmanganeseresistance factorMntX(formerlyYebN).ThepredictedstructuresuggeststhatMntXrepresentsanewfamilyoftransportersexporting Mn.IntheNeisseriagenus,thisexporterispresentandfunctionalinallNmisolatesbutitismutatedinamajorityofNg strainsandcommonlyabsentinnonpathogenicspecies.InNm,Mn2+exportviaMntXregulatestheintracellularMn/Feratio and protects against manganese toxicity that is exacerbated in low iron conditions. MntX is also important for N. meningitidistoresistkillingbyhumanserumandforsurvivalinmicebloodduringsepticemia.Thepresentworkthuspoints tonewcluesaboutMnhomeostasis,itsinterplaywithFemetabolismandtheinfluenceonN.meningitidisphysiologyand pathogenicity. Citation:VeyrierFJ,BonecaIG,CellierMF,TahaM-K(2011)ANovelMetalTransporterMediatingManganeseExport(MntX)RegulatestheMntoFeIntracellular RatioandNeisseriameningitidisVirulence.PLoSPathog7(9):e1002261.doi:10.1371/journal.ppat.1002261 Editor:H.StevenSeifert,NorthwesternUniversityFeinbergSchoolofMedicine,UnitedStatesofAmeri