Inactivation of Francisella tularensis Gene Encoding Putative ABC Transporter Has a Pleiotropic Effect upon Production of Various Glycoconjugates
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- ABC transporter, Francisella tularensis, capsule, glycosylation, lipopolysaccharide,
- MeSH
- ATP-Binding Cassette Transporters genetics metabolism MeSH
- Bacterial Proteins genetics metabolism MeSH
- Chromatography, Liquid MeSH
- Francisella tularensis genetics metabolism pathogenicity MeSH
- Genetic Pleiotropy MeSH
- Glycoconjugates biosynthesis MeSH
- Glycosylation MeSH
- Hexosyltransferases genetics metabolism MeSH
- Host-Pathogen Interactions MeSH
- Lipopolysaccharides biosynthesis MeSH
- Membrane Proteins genetics metabolism MeSH
- Mutation MeSH
- Mice, Inbred BALB C MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Gene Expression Regulation, Bacterial MeSH
- Tandem Mass Spectrometry MeSH
- Tularemia microbiology MeSH
- Gene Silencing MeSH
- Virulence genetics MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- ATP-Binding Cassette Transporters MeSH
- Bacterial Proteins MeSH
- dolichyl-diphosphooligosaccharide - protein glycotransferase MeSH Browser
- Glycoconjugates MeSH
- Hexosyltransferases MeSH
- Lipopolysaccharides MeSH
- Membrane Proteins MeSH
Francisella tularensis, an intracellular pathogen causing the disease tularemia, utilizes surface glycoconjugates such as lipopolysaccharide, capsule, and capsule-like complex for its protection against inhospitable conditions of the environment. Francisella species also possess a functional glycosylation apparatus by which specific proteins are O-glycosidically modified. We here created a mutant with a nonfunctional FTS_1402 gene encoding for a putative glycan flippase and studied the consequences of its disruption. The mutant strain expressed diminished glycosylation similarly to, but to a lesser extent than, that of the oligosaccharyltransferase-deficient ΔpglA mutant. In contrast to ΔpglA, inactivation of FTS_1402 had a pleiotropic effect, leading to alteration in glycosylation and, importantly, to decrease in lipopolysaccharide, capsule, and/or capsule-like complex production, which were reflected by distinct phenotypes in host-pathogen associated properties and virulence potential of the two mutant strains. Disruption of FTS_1402 resulted in enhanced sensitivity to complement-mediated lysis and reduced virulence in mice that was independent of diminished glycosylation. Importantly, the mutant strain induced a protective immune response against systemic challenge with homologous wild-type FSC200 strain. Targeted disruption of genes shared by multiple metabolic pathways may be considered a novel strategy for constructing effective live, attenuated vaccines.
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HU protein is involved in intracellular growth and full virulence of Francisella tularensis
