A defined O-antigen polysaccharide mutant of Francisella tularensis live vaccine strain has attenuated virulence while retaining its protective capacity: Infect.Immun.

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TypeArticle
Journal titleInfect.Immun.
Volume75
Issue5
Pages25912602; # of pages: 12
Subjectadministration & dosage; analysis; Animals; Antibodies; Antibodies,Bacterial; antibody; bacterial; Bacterial Vaccines; Blood; chemistry; electron; EXPRESSION; Female; Francisella tularensis; genetics; Humans; IDENTIFICATION; immunology; Male; Mice; Mice,Inbred BALB C; Microbiology; Microscopy; MOLECULAR; Molecular Sequence Data; mortality; MUTANT; Mutation; O antigen; O Antigens; O-antigen; pathogenicity; POLYSACCHARIDE; prevention & control; recognition; Role; Sequence Analysis,DNA; Serum; Specific Pathogen-Free Organisms; STRAIN; surface; Tularemia; Vaccines; Vaccines,Attenuated; Virulence
AbstractFrancisella tularensis, the causative agent of tularemia, has been designated a CDC category A select agent because of its low infective dose (<10 CFU), its ready transmission by aerosol, and its ability to produce severe morbidity and high mortality. The identification and characterization of this organism's virulence determinants will facilitate the development of a safe and effective vaccine. We report that inactivation of the wbtA-encoded dehydratase of the O-antigen polysaccharide (O-PS) locus of the still-unlicensed live vaccine strain of F. tularensis (LVS) results in a mutant (the LVS wbtA mutant) with remarkably attenuated virulence. Western blot analysis and immune electron microscopy studies associate this loss of virulence with a complete lack of surface O-PS expression. A likely mechanism for attenuation is shown to be the transformation from serum resistance in the wild-type strain to serum sensitivity in the mutant. Despite this significant attenuation in virulence, the LVS wbtA mutant remains immunogenic and confers protective immunity on mice against challenge with an otherwise lethal dose of either F. tularensis LVS or a fully virulent clinical isolate of F. tularensis type B. Recognition and characterization of the pivotal role of O-PS in the virulence of this intracellular bacterial pathogen may have broad implications for the creation of a safe and efficacious vaccine
Publication date
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedNo
NRC numberSEBASTIAN2007
NPARC number9361773
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Record identifierc95cc180-4ad7-4cb6-8b07-e864ba726b5a
Record created2009-07-10
Record modified2016-05-09
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