Meza-Torres Jazmin, Tinevez Jean-Yves, Crouzols Aline, Mary Héloïse, Kim Minhee, Hunault Lise, Chamorro-Rodriguez Susan, Lejal Emilie, Altamirano-Silva Pamela, Groussard Déborah, Gobaa Samy, Peltier Johann, Chassaing Benoit, Dupuy Bruno
Pathogenesis of Bacterial Anaerobes, Department of Microbiology, Institut Pasteur, Université Paris-Cité, UMR-CNRS 6047, Paris, France.
Image Analysis Hub, Department of Cell Biology and Infection, Institut Pasteur, Université Paris Cité, Paris, France.
Gut Microbes. 2025 Dec;17(1):2444411. doi: 10.1080/19490976.2024.2444411. Epub 2024 Dec 24.
Clinical symptoms of 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 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 colonization and display biofilm-like properties by enhancing 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 persistence and risk of relapse.
艰难梭菌感染（CDI）的临床症状从腹泻到假膜性结肠炎不等。治疗CDI的一个主要挑战是复发率高。几项研究将临床菌株产生的CDT二元毒素与较高的复发率联系起来。虽然已知CDT对宿主细胞的作用机制，但其对CDI的确切作用仍不清楚。为了了解CDT在CDI期间的生理作用，我们建立了两种与缺氧相关的肠道模型，即Transwell和微流控肠道芯片系统。两者都用流行菌株UK1 CDT及其同基因CDT突变体进行了挑战。我们报告说，CDT诱导粘蛋白相关的微菌落，这些微菌落通过增强对万古霉素的抗性来增加定殖并表现出类似生物膜的特性。重要的是，在感染小鼠的盲肠和结肠中也观察到了类似生物膜的微菌落。因此，我们的研究表明，CDT诱导类似生物膜的微菌落，增加了持续性和复发风险。
