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Related Experiment Video

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Clostridioides difficile binary toxin CDT induces biofilm-like persisting microcolonies.

Jazmin Meza-Torres1, Jean-Yves Tinevez2, Aline Crouzols1

  • 1Pathogenesis of Bacterial Anaerobes, Department of Microbiology, Institut Pasteur, Université Paris-Cité, UMR-CNRS 6047, Paris, France.

Gut Microbes
|December 24, 2024
PubMed
Summary

Clostridioides difficile toxin (CDT) promotes bacterial microcolonies that resist vancomycin, increasing infection persistence. This finding explains higher relapse rates in patients with CDT-producing C. difficile strains.

Keywords:
CDT binary toxinClostridioides difficile Infection (CDI)antibiotic resistancebiofilmgut persistencemucin-associated microcoloniesrelapse

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Area of Science:

  • Microbiology
  • Gastroenterology
  • Infectious Diseases

Background:

  • Clostridioides difficile infection (CDI) presents with varied symptoms, from diarrhea to colitis.
  • High CDI relapse rates pose a significant clinical challenge.
  • The binary toxin (CDT) from C. difficile is linked to increased relapse, but its precise role remains unclear.

Purpose of the Study:

  • To elucidate the physiological role of CDT in C. difficile pathogenesis.
  • To investigate CDT's contribution to C. difficile colonization and persistence in the gut.

Main Methods:

  • Utilized hypoxic Transwell and Intestine-on-Chip models simulating intestinal conditions.
  • Challenged models with both CDT-producing (CDT+) and non-producing (CDT-) C. difficile strains.
  • Observed microcolony formation and vancomycin resistance in infected mouse models.

Main Results:

  • CDT induces mucin-associated microcolonies, enhancing C. difficile colonization.
  • These microcolonies exhibit biofilm-like properties, increasing vancomycin resistance.
  • Similar biofilm-like microcolonies were found in the colons of infected mice.

Conclusions:

  • CDT promotes the formation of biofilm-like microcolonies, enhancing C. difficile persistence.
  • This mechanism contributes to increased CDI relapse rates.
  • Targeting CDT may offer new strategies for CDI management.