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dc.contributor.authorApicella, Michael A
dc.contributor.authorPost, Deborah MB
dc.contributor.authorFowler, Andrew C
dc.contributor.authorJones, Bradley D
dc.contributor.authorRasmussen, Jed A
dc.contributor.authorHunt, Jason R
dc.contributor.authorImagawa, Sayaka
dc.contributor.authorChoudhury, Biswa
dc.contributor.authorInzana, Thomas J
dc.contributor.authorMaier, Tamara M
dc.contributor.authorFrank, Dara W
dc.contributor.authorZahrt, Thomas C
dc.contributor.authorChaloner, Kathryn
dc.contributor.authorJennings, Michael P
dc.contributor.authorMcLendon, Molly K
dc.contributor.authorGibson, Bradford W
dc.date.accessioned2017-05-03T11:47:34Z
dc.date.available2017-05-03T11:47:34Z
dc.date.issued2010
dc.date.modified2011-03-18T07:02:40Z
dc.identifier.issn1932-6203
dc.identifier.doi10.1371/journal.pone.0011060
dc.identifier.urihttp://hdl.handle.net/10072/36904
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)-a-D-GalNAcAN-(1->4)-a-D-GalNAcAN-(1->?3)-߭D-QuiNAc-(1->2)-߭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 姠of 11B7 protected against a 150 fold lethal challenge of F. tularensis LVS. Active immunization of BALB/c mice with 10 姠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
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent2490708 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoen_AU
dc.publisherPublic Library of Science
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom1
dc.relation.ispartofpageto18
dc.relation.ispartofissue7
dc.relation.ispartofjournalPloS One
dc.relation.ispartofvolume5
dc.rights.retentionY
dc.subject.fieldofresearchMedical and Health Sciences not elsewhere classified
dc.subject.fieldofresearchcode119999
dc.titleIdentification, Characterization and Immunogenicity of an O-Antigen Capsular Polysaccharide of Francisella tularensis
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://www.plos.org/journals/license.html
gro.rights.copyright© 2010 Apicella et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License CCAL. (http://www.plos.org/journals/license.html)
gro.date.issued2010
gro.hasfulltextFull Text
gro.griffith.authorJennings, Michael P.


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