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Pathogens 2012, 1(1), 12-29; doi:10.3390/pathogens1010012
Article

Roles for wbtC, wbtI, and kdtA Genes in Lipopolysaccharide Biosynthesis, Protein Glycosylation, Virulence, and Immunogenicity in Francisella tularensis Strain SCHU S4

1,* , 1
, 2
, 2
 and 1
1 National Research Council Canada, Institute for Biological Sciences, 100 Sussex Drive, Ottawa, ON K1A 1L1, Canada 2 Department of Clinical Microbiology, Clinical Bacteriology, Umeå University, Umeå SE-90185, Sweden
* Author to whom correspondence should be addressed.
Received: 3 August 2012 / Revised: 22 August 2012 / Accepted: 31 August 2012 / Published: 10 September 2012
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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 tularensis subspecies tularensis, strain SCHU S4 in LPS biosynthesis, protein glycosylation, virulence and immunogenicity. One mutant, ∆wbtI, did not elaborate a long chain O-polysaccharide (OPS), was completely avirulent for mice, and failed to induce a protective immune response against challenge with wild type bacteria. Another mutant, ∆wbtC, 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, ∆kdtA, 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.
Keywords: Francisella tularensis; lipopolysaccharide; glycosylation; virulence Francisella tularensis; lipopolysaccharide; glycosylation; virulence
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Twine, S.M.; Vinogradov, E.; Lindgren, H.; Sjostedt, A.; Conlan, J.W. Roles for wbtC, wbtI, and kdtA Genes in Lipopolysaccharide Biosynthesis, Protein Glycosylation, Virulence, and Immunogenicity in Francisella tularensis Strain SCHU S4. Pathogens 2012, 1, 12-29.

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