A Novel Group of Moraxella catarrhalis UspA Proteins Mediates Cellular Adhesion via CEACAMs and Vitronectin 英文参考文献.docVIP

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A Novel Group of Moraxella catarrhalis UspA Proteins Mediates Cellular Adhesion via CEACAMs and Vitronectin 英文参考文献.doc

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A Novel Group of Moraxella catarrhalis UspA Proteins Mediates Cellular Adhesion via CEACAMs and Vitronectin 英文参考文献

ANovelGroupofMoraxellacatarrhalisUspAProteins MediatesCellularAdhesionviaCEACAMsandVitronectin DarrylJ.Hill*,CherylWhittles,MumtazVirji* SchoolofCellularMolecularMedicine,UniversityofBristol,Bristol,UnitedKingdom Abstract Moraxellacatarrhalis(Mx)isacommoncauseofotitismediaandexacerbationofchronicobstructivepulmonarydisease,an increasingworldwideproblem.SurfaceproteinsUspA1andUspA2ofMxbindtoanumberofhumanreceptorsandmay function in pathogenesis. Genetic recombination events in the pathogen can generate hybrid proteins termed UspA2H. However,whethercertainkeyfunctions(e.g.UspA1-specificCEACAMbinding)canbeexchangedbetweentheseadhesin familiesremainsunknown.Inthisstudy,wehaveshownthatMxcanincorporatetheUspA1CEACAM1-bindingregionnot only into rare UspA1 proteins devoid of CEACAM-binding ability, but also into UspA2 which normally lack this capacity. Further,ascreenofMxisolatesrevealedthepresenceofnovelUspA2Variantproteins(UspA2V)in,14%oftheCEACAM- bindingpopulation.WedemonstratethattheexpressionofUspA2/2VwiththeCEACAM-bindingdomainenableMxtobind both to cell surface CEACAMs and to integrins, the latter via vitronectin. Such properties of UspA2/2V have not been reportedtodate.ThestudiesdemonstratethattheUspAfamilyismuchmoreheterogeneousthanpreviouslybelievedand illustratetheinvivopotentialforexchangeoffunctionalregionsbetweenUspAproteinswhichcouldconveynoveladhesive functionswhilstenhancingimmuneevasion. Citation:HillDJ,WhittlesC,VirjiM(2012)ANovelGroupofMoraxellacatarrhalisUspAProteinsMediatesCellularAdhesionviaCEACAMsandVitronectin.PLoS ONE7(9):e45452.doi:10.1371/journal.pone.0045452 Editor:MikaelSkurnik,UniversityofHelsinki,Finland ReceivedJune8,2012;AcceptedAugust22,2012;PublishedSeptember25,2012 Copyright:?2012Hilletal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted use,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: Thestudy was supported by agrant fro