Roles for wbtC, wbtI, and kdtA Genes in Lipopolysaccharide Biosynthesis, Protein Glycosylation, Virulence, and Immunogenicity in Francisella tularensis Strain SCHU S4 英文参考文献.docVIP

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Roles for wbtC, wbtI, and kdtA Genes in Lipopolysaccharide Biosynthesis, Protein Glycosylation, Virulence, and Immunogenicity in Francisella tularensis Strain SCHU S4 英文参考文献.doc

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

Pathogens 2012, 1, 12-29; doi:10.3390/pathogens1010012 OPEN ACCESS pathogens ISSN 2076-0817 /journal/pathogens Article Roles for wbtC, wbtI, and kdtA Genes in Lipopolysaccharide Biosynthesis, Protein Glycosylation, Virulence, and Immunogenicity in Francisella tularensis Strain SCHU S4 Susan M. Twine 1,*, Evguenii Vinogradov 1, Helena Lindgren 2, Anders Sjostedt 2 and J. Wayne Conlan 1 1 National Research Council Canada, Institute for Biological Sciences, 100 Sussex Drive, Ottawa, ON K1A 1L1, Canada; E-Mails: evguennii.vinogradov@nrc-cnrc.gc.ca (E.V.); wayne.conlan@nrc-cnrc.gc.ca (J.W.C.) 2 Department of Clinical Microbiology, Clinical Bacteriology, Ume? University, Ume? SE-90185, Sweden; E-Mails: helena.lindgren@climi.umu.se (H.L.); anders.sjostedt@climi.umu.se (A.S.) * Author to whom correspondence should be addressed; E-Mail: susan.twine@nrc.ca; Tel.: +1-613-993-8829; Fax: +1-613-952-9092. Received: 3 August 2012; in revised form: 22 August 2012 / Accepted: 31 August 2012 / Published: 10 September 2012 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