Epistatic Relationships between sarA and agr in Staphylococcus aureus Biofilm Formation 英文参考文献.docVIP

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Epistatic Relationships between sarA and agr in Staphylococcus aureus Biofilm Formation 英文参考文献.doc

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Epistatic Relationships between sarA and agr in Staphylococcus aureus Biofilm Formation 英文参考文献

EpistaticRelationshipsbetweensarAandagrin StaphylococcusaureusBiofilmFormation KarenE.Beenken1.,LaraN.Mrak1.,LindaM.Griffin1,AgnieszkaK.Zielinska1,LindseyN.Shaw2,KellyC. Rice3,AlexanderR.Horswill4,KennethW.Bayles5,MarkS.Smeltzer1* 1DepartmentofMicrobiologyandImmunology,UniversityofArkansasforMedicalSciences,LittleRock,Arkansas,UnitedStatesofAmerica,2DepartmentofBiology, UniversityofSouthFlorida,Tampa,Florida,UnitedStatesofAmerica,3DepartmentofMicrobiologyandCellScience,UniversityofFlorida,Gainesville,Florida,United StatesofAmerica,4DepartmentofMicrobiology,UniversityofIowa,IowaCity,Iowa,UnitedStatesofAmerica,5DepartmentofPathologyandMicrobiology,Universityof NebraskaMedicalCenter,Omaha,Nebraska,UnitedStatesofAmerica Abstract Background: The accessory gene regulator (agr) and staphylococcal accessory regulator (sarA) play opposing roles in Staphylococcus aureus biofilm formation. There is mounting evidence to suggest that these opposing roles are therapeuticallyrelevantinthatmutationofagrresultsinincreasedbiofilmformationanddecreasedantibioticsusceptibility whilemutationofsarAhastheoppositeeffect.TotheextentthatinductionofagrorinhibitionofsarAcouldpotentiallybe usedtolimitbiofilmformation,thismakesitimportanttounderstandtheepistaticrelationshipsbetweenthesetwoloci. Methodology/PrincipalFindings:WegeneratedisogenicsarAandagrmutantsinclinicalisolatesofS.aureusandassessedthe relativeimpactonbiofilmformation.Mutationofagrresultedinanincreasedcapacitytoformabiofilminthe8325-4laboratory strainRN6390buthadlittleimpactinclinicalisolatesS.aureus.Incontrast,mutationofsarAresultedinareducedcapacityto formabiofilminallclinicalisolatesirrespectiveofthefunctionalstatusofagr.ThissuggeststhattheregulatoryroleofsarAin biofilmformationisindependentoftheinteractionbetweensarAandagrandthatsarAisepistatictoagrinthiscontext.This was confirmed by demonstrating that restoration of sarA function restored the ability to form a biofilm even in the correspondingagrmutants.MutationofsarAincli