Characterization of flagellum and toxin phase variation in Clostridioides difficile ribotype 012 isolates

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  • Anjuwon-Foster, B.R.
    • School of Medicine, Department of Microbiology and Immunology
  • Maldonado-Vazquez, N.
    • School of Medicine, Department of Microbiology and Immunology
  • Tamayo, R.
    • School of Medicine, Department of Microbiology and Immunology
Abstract
  • Clostridioides difficile causes diarrheal diseases mediated in part by the secreted toxins TcdA and TcdB. C. difficile produces flagella that also contribute to motility and bacterial adherence to intestinal cells during infection. Flagellum expression and toxin gene expression are linked via the flagellar alternative sigma factor, SigD. Recently, we identified a flagellar switch upstream of the early flagellar biosynthesis operon that mediates phase variation of both flagellum and toxin production in C. difficile strain R20291. However, we were unable to detect flagellar switch inversion in C. difficile strain 630, a ribotype 012 strain commonly used in research labs, suggesting that the strain is phase locked. To determine whether a phase-locked flagellar switch is limited to 630 or present more broadly in ribotype 012 strains, we assessed the frequency and phenotypic outcomes of flagellar switch inversion in multiple C. difficile ribotype 012 isolates. The laboratory-adapted strain JIR8094, a derivative of strain 630, and six clinical and environmental isolates were all found to be phase-off, nonmotile, and attenuated for toxin production. We isolated low-frequency motile derivatives of JIR8094 with partial recovery of motility and toxin production and found that additional changes in JIR8094 impact these processes. The clinical and environmental isolates varied considerably in the frequency by which flagellar phase-on derivatives arose, and these derivatives showed fully restored motility and toxin production. Taken together, these results demonstrate heterogeneity in flagellar and toxin phase variation among C. difficile ribotype 012 strains and perhaps other ribotypes, which could impact disease progression and diagnosis.
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  • Article
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  • In Copyright
Journal title
  • Journal of Bacteriology
Journal volume
  • 200
Journal issue
  • 14
Language
  • English
ISSN
  • 0021-9193
Publisher
  • American Society for Microbiology

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