The post-translational modification of the Clostridium difficile flagellin affects motility, cell surface properties and virulence

From National Research Council Canada

DOIResolve DOI: https://doi.org/10.1111/mmi.12755
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Name affiliation
  1. National Research Council of Canada. Human Health Therapeutics
FormatText, Article
Journal titleMolecular Microbiology
ISSN0950-382X
1365-2958
Volume94
Issue2
Pages272–289
Abstract
Clostridium difficile is a prominent nosocomial pathogen, proliferating and causing enteric disease in individuals with a compromised gut microflora. We characterized the post-translational modification of flagellin in C. difficile 630. The structure of the modification was solved by nuclear magnetic resonance and shown to contain an N-acetylglucosamine substituted with a phosphorylated N-methyl-l-threonine. A reverse genetics approach investigated the function of the putative four-gene modification locus. All mutants were found to have truncated glycan structures by LC-MS/MS, taking into account bioinformatic analysis, we propose that the open reading frame CD0241 encodes a kinase involved in the transfer of the phosphate to the threonine, the CD0242 protein catalyses the addition of the phosphothreonine to the N-acetylglucosamine moiety and CD0243 transfers the methyl group to the threonine. Some mutations affected motility and caused cells to aggregate to each other and abiotic surfaces. Altering the structure of the flagellin modification impacted on colonization and disease recurrence in a murine model of infection, showing that alterations in the surface architecture of C. difficile vegetative cells can play a significant role in disease. We show that motility is not a requirement for colonization, but that colonization was compromised when the glycan structure was incomplete.
Publication date
PublisherWiley
LanguageEnglish
Peer reviewedYes
NPARC number23002066
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Record identifier83936343-5bee-40a0-86f7-b5824cc155ba
Record created2017-08-02
Record modified2020-04-22
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