Number of the records: 1  

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

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    SYSNO ASEP0472623
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleInactivation of Francisella tularensis Gene Encoding Putative ABC Transporter Has a Pleiotropic Effect upon Production of Various Glycoconjugates
    Author(s) Daňková, V. (CZ)
    Balonová, L. (CZ)
    Link, M. (CZ)
    Strašková, Adéla (MBU-M)
    Sheshko, V . (CZ)
    Stulík, J. (CZ)
    Source TitleJournal of Proteome Research. - : American Chemical Society - ISSN 1535-3893
    Roč. 15, č. 2 (2016), s. 510-524
    Number of pages15 s.
    Languageeng - English
    CountryUS - United States
    KeywordsFrancisella tularensis ; glycosylation ; lipopolysaccharide
    Subject RIVEE - Microbiology, Virology
    Institutional supportMBU-M - RVO:61388971
    UT WOS000369771700015
    EID SCOPUS84957658572
    DOI10.1021/acs.jproteome.5b00864
    AnnotationFrancisella 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.
    WorkplaceInstitute of Microbiology
    ContactEliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231
    Year of Publishing2017
Number of the records: 1  

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