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dc.contributor.authorApicella, Michael A.en_US
dc.contributor.authorPost, Deborah M. B.en_US
dc.contributor.authorFowler, Andrew C.en_US
dc.contributor.authorJones, Bradley D.en_US
dc.contributor.authorRasmussen, Jed A.en_US
dc.contributor.authorHunt, Jason R.en_US
dc.contributor.authorImagawa, Sayakaen_US
dc.contributor.authorChoudhury, Biswaen_US
dc.contributor.authorInzana, Thomas J.en_US
dc.contributor.authorMaier, Tamara M.en_US
dc.contributor.authorFrank, Dara W.en_US
dc.contributor.authorZahrt, Thomas C.en_US
dc.contributor.authorChaloner, Kathrynen_US
dc.contributor.authorJennings, Michael P.en_US
dc.contributor.authorMcLendon, Molly K.en_US
dc.contributor.authorGibson, Bradford W.en_US
dc.date.accessioned2018-11-12T20:11:11Z
dc.date.available2018-11-12T20:11:11Z
dc.date.issued2010-07-06en_US
dc.identifier.othere11060en_US
dc.identifier.urihttp://hdl.handle.net/10919/85820
dc.description.abstractCapsular polysaccharides are important factors in bacterial pathogenesis and have been the target of a number of successful vaccines. Francisella tularensis has been considered to express a capsular antigen but none has been isolated or characterized. We have developed a monoclonal antibody, 11B7, which recognizes the capsular polysaccharide of F. tularensis migrating on Western blot as a diffuse band between 100 kDa and 250 kDa. The capsule stains poorly on SDS-PAGE with silver stain but can be visualized using ProQ Emerald glycoprotein stain. The capsule appears to be highly conserved among strains of F. tularensis as antibody 11B7 bound to the capsule of 14 of 14 F. tularensis type A and B strains on Western blot. The capsular material can be isolated essentially free of LPS, is phenol and proteinase K resistant, ethanol precipitable and does not dissociate in sodium dodecyl sulfate. Immunoelectron microscopy with colloidal gold demonstrates 11B7 circumferentially staining the surface of F. tularensis which is typical of a polysaccharide capsule. Mass spectrometry, compositional analysis and NMR indicate that the capsule is composed of a polymer of the tetrasaccharide repeat, 4)-α-D-GalNAcAN-(1->4)-α-D-GalNAcAN-(1->3)-β-D-QuiNAc-(1->2)-β-D-Qui4NFm-(1-, which is identical to the previously described F. tularensis O-antigen subunit. This indicates that the F. tularensis capsule can be classified as an O-antigen capsular polysaccharide. Our studies indicate that F. tularensis O-antigen glycosyltransferase mutants do not make a capsule. An F. tularensis acyltransferase and an O-antigen polymerase mutant had no evidence of an O-antigen but expressed a capsular antigen. Passive immunization of BALB/c mice with 75 µg of 11B7 protected against a 150 fold lethal challenge of F. tularensis LVS. Active immunization of BALB/c mice with 10 µg of capsule showed a similar level of protection. These studies demonstrate that F. tularensis produces an O-antigen capsule that may be the basis of a future vaccine.en_US
dc.format.mimetypeapplication/pdfen_US
dc.language.isoen_USen_US
dc.publisherPLOSen_US
dc.rightsCreative Commons Attribution 4.0 Internationalen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.titleIdentification, Characterization and Immunogenicity of an O-Antigen Capsular Polysaccharide of Francisella tularensisen_US
dc.typeArticle - Refereeden_US
dc.description.versionPeer Revieweden_US
dc.title.serialPLOS ONEen_US
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0011060en_US
dc.identifier.volume5en_US
dc.identifier.issue7en_US
dc.type.dcmitypeTexten_US
dc.identifier.pmid20625403en_US
dc.identifier.eissn1932-6203en_US


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Creative Commons Attribution 4.0 International
License: Creative Commons Attribution 4.0 International