Adaptation and Preadaptation of Salmonella enterica to Bile 英文参考文献.docVIP

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Adaptation and Preadaptation of Salmonella enterica to Bile 英文参考文献.doc

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Adaptation and Preadaptation of Salmonella enterica to Bile 英文参考文献

AdaptationandPreadaptationofSalmonellaentericato Bile SaraB.Herna′ndez1,IgnacioCota1,AdrienDucret2,LaurentAussel2,JosepCasadesu′s1* 1DepartamentodeGene′tica, UniversidaddeSevilla,Sevilla,Spain,2LaboratoiredeChimieBacte′rienne, CNRS-UPR9043,Aix-MarseilleUniversity,Marseille,France Abstract Bilepossessesantibacterialactivitybecausebilesaltsdisruptmembranes,denatureproteins,anddamageDNA.Thisstudy describesmechanismsemployedbythebacteriumSalmonellaentericatosurvivebile.Sublethalconcentrationsofthebile salt sodium deoxycholate (DOC) adapt Salmonella to survive lethal concentrations of bile. Adaptation seems to be associated to multiple changes in gene expression, which include upregulation of the RpoS-dependent general stress responseandotherstressresponses.Thecrucialroleofthegeneralstressresponseinadaptationtobileissupportedbythe observationthatRpoS2mutantsarebile-sensitive.Whileadaptationtobileinvolvesaresponsebythebacterialpopulation, individual cells can become bile-resistant without adaptation: plating of a non-adapted S. enterica culture on medium containingalethalconcentrationofbileyieldsbile-resistantcoloniesatfrequenciesbetween1026and1027percelland generation.Fluctuationanalysisindicatesthatsuchcoloniesderivefrombile-resistantcellspresentinthepreviousculture.A fractionofsuchisolatesarestable,indicatingthatbileresistancecanbeacquiredbymutation.Fullgenomesequencingof bile-resistantmutantsshowsthatalterationofthelipopolysaccharidetransportmachineryisafrequentcauseofmutational bileresistance.However,selectiononlethalconcentrationsofbilealsoprovidesbile-resistantisolatesthatarenotmutants. Weproposethatsuchisolatesderivefromrarecellswhosephysiologicalstatepermittedsurvivaluponencounteringbile. This view is supported by single cell analysis of gene expression using a microscope fluidic system: batch cultures of Salmonella contain cells that activate stress response genes in the absence of DOC. This phenomenon underscores the existence of phenotypic heterogeneity