Attenuated Salmonella Typhimurium Lacking the Pathogenicity Island-2 Type 3 Secretion System Grow to High Bacterial Numbers inside Phagocytes in Mice.docVIP

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Attenuated Salmonella Typhimurium Lacking the Pathogenicity Island-2 Type 3 Secretion System Grow to High Bacterial Numbers inside Phagocytes in Mice.doc

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Attenuated Salmonella Typhimurium Lacking the Pathogenicity Island-2 Type 3 Secretion System Grow to High Bacterial Numbers inside Phagocytes in Mice

AttenuatedSalmonellaTyphimuriumLackingthe PathogenicityIsland-2Type3SecretionSystemGrowto HighBacterialNumbersinsidePhagocytesinMice AndrewJ.Grant*,FionaJ.E.Morgan,TrevelyanJ.McKinley,GemmaL.Foster,DuncanJ.Maskell, PietroMastroeni DepartmentofVeterinaryMedicine,UniversityofCambridge,Cambridge,UnitedKingdom Abstract Intracellular replication within specialized vacuoles and cell-to-cell spread in the tissue are essential for the virulence of Salmonellaenterica.Byobservinginfectiondynamicsatthesingle-celllevelinvivo,wehavediscoveredthattheSalmonella pathogenicityisland2(SPI-2)type3secretorysystem(T3SS)isdispensableforgrowthtohighintracellulardensities.This challengestheconceptthatintracellularreplicationabsolutelyrequiresproteinsdeliveredbySPI-2T3SS,whichhasbeen derivedlargelybyinferencefrominvitrocellexperimentsandfromunrefinedmeasurementofnetgrowthinmouseorgans. Furthermore,weinferfromourdatathattheSPI-2T3SSmediatesexitfrominfectedcells,withconsequentformationof newinfectionfociresultinginbacterialspread inthetissues.ThissuggestsanewroleforSPI-2 invivoasamediator of bacterialspreadinthebody.Inaddition,wedemonstratethatverysimilarnetgrowthratesofattenuatedsalmonellaein organscanbederivedfromverydifferentunderlyingintracellulargrowthdynamics. Citation:GrantAJ,MorganFJE,McKinleyTJ,FosterGL,MaskellDJ,etal.(2012)AttenuatedSalmonellaTyphimuriumLackingthePathogenicityIsland-2Type3 SecretionSystemGrowtoHighBacterialNumbersinsidePhagocytesinMice.PLoSPathog8(12):e1003070.doi:10.1371/journal.ppat.1003070 Editor:DeniseM.Monack,StanfordUniversitySchoolofMedicine,UnitedStatesofAmerica ReceivedJuly26,2012;AcceptedOctober19,2012;PublishedDecember6,2012 Copyright: ? 2012 Grant et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwassupportedbyaMedicalResearchCouncil(MRC)grantG0801161a