<i>Clostridioides difficile</i> binary toxin CDT induces biofilm-like persisting microcolonies
Clinical symptoms of <i>Clostridioides difficile</i> infection (CDI) range from diarrhea to pseudomembranous colitis. A major challenge in managing CDI is the high rate of relapse. Several studies correlate the production of CDT binary toxin by clinical strains of <i>C. difficile</i> with higher relapse rates. Although the mechanism of action of CDT on host cells is known, its exact contribution to CDI is still unclear. To understand the physiological role of CDT during CDI, we established two hypoxic relevant intestinal models, Transwell and Microfluidic Intestine-on-Chip systems. Both were challenged with the epidemic strain UK1 CDT<sup>+</sup> and its isogenic CDT<sup>-</sup> mutant. We report that CDT induces mucin-associated microcolonies that increase <i>C. difficile</i> colonization and display biofilm-like properties by enhancing <i>C. difficile</i> resistance to vancomycin. Importantly, biofilm-like microcolonies were also observed in the cecum and colon of infected mice. Hence, our study shows that CDT induces biofilm-like microcolonies, increasing <i>C. difficile</i> persistence and risk of relapse.
Authors
- Samy Gobaa (ORCID: https://orcid.org/0000-0002-0125-8674)
- Jazmín Meza‐Torres (ORCID: https://orcid.org/0000-0003-2603-8544)
- Lise Hunault (ORCID: https://orcid.org/0009-0003-1871-6058)
- Johann Peltier (ORCID: https://orcid.org/0000-0003-3207-9465)
- Benoît Chassaing (ORCID: https://orcid.org/0000-0002-4285-769X)
- Héloïse Mary (ORCID: https://orcid.org/0000-0003-1171-3260)
- Pamela Altamirano-Silva (ORCID: https://orcid.org/0009-0001-3940-5801)
- Déborah Groussard (ORCID: https://orcid.org/0000-0003-0664-1274)
- Jean-Yves Tinévez (ORCID: https://orcid.org/0000-0002-0998-4718)
- Aline Crouzols
- Emilie Lejal (ORCID: https://orcid.org/0000-0001-8904-2351)
- Bruno Dupuy (ORCID: https://orcid.org/0000-0001-7176-8453)
- Susan Chamorro-Rodriguez (ORCID: https://orcid.org/0000-0002-8499-1694)
- Min-Hee Kim (ORCID: https://orcid.org/0000-0002-1026-4232)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Institut Pasteur (FR)
- Université Paris Cité (FR)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Université Paris-Saclay (FR)
- Universidad de Costa Rica (CR)
- Sorbonne Paris Cité (FR)
- Institut de Biologie Intégrative de la Cellule (FR)
- Département Santé Animale (FR)
- CEA Paris-Saclay (FR)
Publication Details
- Journal
- Gut Microbes
- Published
- 2024-12-24
- DOI
- https://doi.org/10.1080/19490976.2024.2444411
- Citations
- 10
- Primary Topic
- Clostridium difficile and Clostridium perfringens research
- Type
- article
- Field-Weighted Citation Impact
- 3.89
Funders
- Institut Pasteur