Inactivation of Francisella tularensis Gene Encoding Putative ABC Transporter Has a Pleiotropic Effect upon Production of Various Glycoconjugates
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
- Klíčová slova
- ABC transporter, Francisella tularensis, capsule, glycosylation, lipopolysaccharide,
- MeSH
- ABC transportéry genetika metabolismus MeSH
- bakteriální proteiny genetika metabolismus MeSH
- chromatografie kapalinová MeSH
- Francisella tularensis genetika metabolismus patogenita MeSH
- genetická pleiotropie MeSH
- glykokonjugáty biosyntéza MeSH
- glykosylace MeSH
- hexosyltransferasy genetika metabolismus MeSH
- interakce hostitele a patogenu MeSH
- lipopolysacharidy biosyntéza MeSH
- membránové proteiny genetika metabolismus MeSH
- mutace MeSH
- myši inbrední BALB C MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- regulace genové exprese u bakterií MeSH
- tandemová hmotnostní spektrometrie MeSH
- tularemie mikrobiologie MeSH
- umlčování genů MeSH
- virulence genetika MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ABC transportéry MeSH
- bakteriální proteiny MeSH
- dolichyl-diphosphooligosaccharide - protein glycotransferase MeSH Prohlížeč
- glykokonjugáty MeSH
- hexosyltransferasy MeSH
- lipopolysacharidy MeSH
- membránové proteiny 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.
Citace poskytuje Crossref.org
HU protein is involved in intracellular growth and full virulence of Francisella tularensis
