Protective Efficacy of BCG Overexpressing an L,D-Transpeptidase against M. tuberculosis Infection 英文参考文献.docVIP

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Protective Efficacy of BCG Overexpressing an L,D-Transpeptidase against M. tuberculosis Infection 英文参考文献.doc

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Protective Efficacy of BCG Overexpressing an L,D-Transpeptidase against M. tuberculosis Infection 英文参考文献

ProtectiveEfficacyofBCGOverexpressinganL,D- TranspeptidaseagainstM.tuberculosisInfection ScottT.Nolan,GyanuLamichhane* DepartmentofMedicine,JohnsHopkinsUniversitySchoolofMedicine,Baltimore,Maryland,UnitedStatesofAmerica Abstract Background:M.bovisBacilleCalmette-Gue′rin(BCG),currentlytheonlyavailablevaccineagainsttuberculosis(TB),failsto adequatelyprotectindividualsfromactiveandlatentTBinfection.Newvaccinesaredesperatelyneededtodecreasethe worldwideburdenofTB. MethodsandFindings:WecreatedarecombinantstrainofBCGthatoverproducesanL,D-transpeptidaseinordertoalter thebacterialpeptidoglycanlayerandconsequentlyincreasetheabilityofthisimmunogentoprotectagainstvirulentM. tuberculosis(Mtb).WedemonstratethatthisnovelrecombinantBCGprotectsmiceagainstvirulentMtbatleastaswellas controlBCG,asmeasuredbyitsabilitytoreducebacterialburdeninlungsandspleen,reducelunghistopathology,and prolongsurvival.AnutrientstarvedrecombinantBCGpreparation,whileofferingcomparableprotection,elicitedaresponse characterizedbyelevatedlevelsofselectTh1cytokines. Conclusions: Recombinant BCG overexpressing a L,D-transpeptidase that is nutrient starved elicits a stronger Th1 type responseandisatleastasprotectiveasparentBCG.Resultsfromthisstudysuggestthatnutrientstarvationtreatmentof live BCG vaccines should be further investigated as a way to increase host induction of Th-1 related cytokines in the developmentofexperimentalanti-TBvaccines. Citation: Nolan ST, Lamichhane G (2010) Protective Efficacy of BCG Overexpressing an L,D-Transpeptidase against M. tuberculosis Infection. PLoS ONE 5(10): e13773.doi:10.1371/journal.pone.0013773 Editor:KatyC.Kao,TexasAMUniversity,UnitedStatesofAmerica ReceivedJune25,2010;AcceptedOctober12,2010;PublishedOctober29,2010 Copyright:?2010Nolan,Lamichhane.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: This work w