title: Roles forwbtC,wbtI, andkdtAGenes in Lipopolysaccharide Biosynthesis, Protein Glycosylation, Virulence, and Immunogenicity inFrancisella tularensis2Strain SCHU S4.
abstract: Using a strategy of gene deletion mutagenesis, we have examined the roles of genes putatively involved in lipopolysaccharide biosynthesis in the virulent facultative intracellular bacterial pathogen,Francisella tularensissubspeciestularensis, strain SCHU S4 in LPS biosynthesis, protein glycosylation, virulence and immunogenicity. One mutant,ΔwbtI, did not elaborate a long chainO-polysaccharide (OPS), was completely avirulent for mice, and failed to induce a protective immune response against challenge with wild type bacteria. Another mutant,ΔwbtC, produced a long chain OPS with altered chemical and electrophoretic characteristics. This mutant showed markedly reduced glycosylation of several known glycoproteins. Additionally this mutant was highly attenuated, and elicited a protective immune response against systemic, but not respiratory challenge with wild type SCHU S4. A third mutant,ΔkdtA, produced an unconjugated long chain OPS, lacking a detectable core structure, and which was not obviously expressed at the surface. It was avirulent and elicited partial protection against systemic challenge only.
authors.affiliation: National Research Council Canada, Institute for Biological Sciences, 100 Sussex Drive, Ottawa, ON K1A 1L1, Canada.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Twine
authors.affiliation: National Research Council Canada, Institute for Biological Sciences, 100 Sussex Drive, Ottawa, ON K1A 1L1, Canada.
authors.forename: Evguenii
authors.initials: E
authors.lastname: Vinogradov
authors.affiliation: Department of Clinical Microbiology, Clinical Bacteriology, Umeå University, Umeå SE-90185, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Lindgren
authors.affiliation: Department of Clinical Microbiology, Clinical Bacteriology, Umeå University, Umeå SE-90185, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Sjostedt
authors.affiliation: National Research Council Canada, Institute for Biological Sciences, 100 Sussex Drive, Ottawa, ON K1A 1L1, Canada.
authors.forename: J Wayne
authors.initials: JW
authors.lastname: Conlan
keywords: Francisella tularensis; glycosylation; lipopolysaccharide; virulence