Pathogenesis of Bacterial Anaerobes, Department of Microbiology, Institut Pasteur, Université Paris-Cité, UMR-CNRS 6047, Paris, France
Jean-Yves Tinevez
Image Analysis Hub, Department of Cell Biology and Infection, Institut Pasteur, Université Paris Cité, Paris, France
Aline Crouzols
Pathogenesis of Bacterial Anaerobes, Department of Microbiology, Institut Pasteur, Université Paris-Cité, UMR-CNRS 6047, Paris, France
Héloïse Mary
Biomaterials and Microfluidics Core Facility, Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, Paris, France
Minhee Kim
Biomaterials and Microfluidics Core Facility, Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, Paris, France
Lise Hunault
Antibodies in Therapy and Pathology, Department of Immunology, Institut Pasteur, Paris, France
Susan Chamorro-Rodriguez
Pathogenesis of Bacterial Anaerobes, Department of Microbiology, Institut Pasteur, Université Paris-Cité, UMR-CNRS 6047, Paris, France
Emilie Lejal
Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, Gif-sur-Yvette, France
Pamela Altamirano-Silva
Centro de Investigación en Enfermedades Tropicales, Universidad de Costa Rica, San José, Costa Rica
Déborah Groussard
Animalerie Centrale, Institut Pasteur, Paris, France
Samy Gobaa
Biomaterials and Microfluidics Core Facility, Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, Paris, France
Johann Peltier
Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, Gif-sur-Yvette, France
Benoit Chassaing
Microbiome-Host Interactions, Department of Microbiology, Institut Pasteur, Université Paris Cité, INSERM U1306, Paris, France
Bruno Dupuy
Pathogenesis of Bacterial Anaerobes, Department of Microbiology, Institut Pasteur, Université Paris-Cité, UMR-CNRS 6047, Paris, France
Clinical symptoms of Clostridioides difficile 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 C. difficile 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+ and its isogenic CDT− mutant. We report that CDT induces mucin-associated microcolonies that increase C. difficile colonization and display biofilm-like properties by enhancing C. difficile 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 C. difficile persistence and risk of relapse.
