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An Atypical Riboflavin Pathway Is Essential for Brucella abortus Virulence 英文参考文献
AnAtypicalRiboflavinPathwayIsEssentialforBrucella
abortusVirulence
Herna′nRuyBonomi1.,Mar?′aIne′sMarchesini2.,Sebastia′nKlinke1,JuanE.Ugalde2,VanesaZylberman1,
RodolfoA.Ugalde2,DiegoJ.Comerci2,FernandoAlbertoGoldbaum1*
1Fundacio′nInstitutoLeloir-CONICET,BuenosAires,Argentina,2InstitutodeInvestigacionesBiotecnolo′gicas-CONICET,UniversidadNacionaldeGeneralSanMart?′n,San
Mart?′n,BuenosAires,Argentina
Abstract
BrucellosisisaworldwidezoonosisthataffectslivestockandhumansandiscausedbycloselyrelatedBrucellaspp. ,which
areadaptedtointracellularlifewithincellsofalargevarietyofmammals.Brucellacanbeconsideredafurtivepathogenthat
infects professional and non-professional phagocytes. In these cells Brucella survives in a replicative niche, which is
characterizedforhavingaverylowoxygentensionandbeingdeprivedfromnutrientssuchasaminoacidsandvitamins.
Among these vitamins, we have focused on riboflavin (vitamin B2). Flavin metabolism has been barely implicated in
bacterial virulence. We have recently described that Brucella and other Rhizobiales bear an atypical riboflavin metabolic
pathway. In the present work we analyze the role of the flavin metabolism on Brucella virulence. Mutants on the two
lumazine synthases (LS) isoenzymes RibH1 and RibH2 and a double RibH mutant were generated. These mutants and
different complemented strains were tested for viability and virulence in cells and in mice. In this fashion we have
established that at least one LS must be present for B. abortus survival and that RibH2 and not RibH1 is essential for
intracellularsurvivalduetoitsLSactivityinvivo.Insummary,weshowthatriboflavinbiosynthesisisessentialforBrucella
survivalinsidecellsorinmice.Theseresultshighlightthepotentialuseofflavinbiosyntheticpathwayenzymesastargets
forthechemotherapyofbrucellosis.
Citation:BonomiHR,MarchesiniMI,KlinkeS,UgaldeJE,ZylbermanV,etal.(2010)AnAtypicalRiboflavinPathwayIsEssentialforBrucellaabortusVirulence.PLoS
ONE5(2):e9435.doi:10.1371/journal.pone.0009435
Editor:Michae
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