Inactivation of Francisella tularensis Gene Encoding Putative ABC Transporter Has a Pleiotropic Effect upon Production of Various Glycoconjugates

0472623 - MBÚ 2017 RIV US eng J - Článek v odborném periodiku
Daňková, V. - Balonová, L. - Link, M. - Strašková, Adéla - Sheshko, V . - Stulík, J.
Inactivation of Francisella tularensis Gene Encoding Putative ABC Transporter Has a Pleiotropic Effect upon Production of Various Glycoconjugates.
Journal of Proteome Research. Roč. 15, č. 2 (2016), s. 510-524. ISSN 1535-3893. E-ISSN 1535-3907
Institucionální podpora: RVO:61388971
Klíčová slova: Francisella tularensis * glycosylation * lipopolysaccharide
Kód oboru RIV: EE - Mikrobiologie, virologie
Impakt faktor: 4.268, rok: 2016

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 Delta pglA mutant. In contrast to Delta pglA, 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.
Trvalý link: http://hdl.handle.net/11104/0269882