title: Clostridium difficile toxins facilitate bacterial colonization by modulating the fence and gate function of colonic epithelium.
abstract: The contribution of Clostridium difficile toxin A and B (TcdA and TcdB) to cellular intoxication has been studied extensively, but their impact on bacterial colonization remains unclear. By setting up 2- and 3-dimensional in vitro models of polarized gut epithelium, we investigated how C. difficile infection is affected by host cell polarity and whether TcdA and TcdB contribute to such events. Indeed, we observed that C. difficile adhesion and penetration of the mucosal barrier are substantially enhanced in poorly polarized or ethylene glycol tetraacetic acid-treated cells, indicating that bacteria bind preferentially to the basolateral (BL) cell surface. In this context, we demonstrated that sub-lethal concentrations of C. difficile TcdA are able to alter cell polarity by causing redistribution of plasma membrane components between distinct surface domains. Taken together, the data suggest that toxin-mediated modulation of host cell organization may account for the capacity of this opportunistic pathogen to gain access to BL receptors, leading to a successful colonization of the colonic mucosa.
authors.affiliation: Novartis Vaccines and Diagnostics, Via Fiorentina 1, Siena, Italy.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kasendra
authors.forename: Riccardo
authors.initials: R
authors.lastname: Barrile
authors.forename: Rosanna
authors.initials: R
authors.lastname: Leuzzi
authors.forename: Marco
authors.initials: M
authors.lastname: Soriani
mesh_terms: D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000633:toxicity*; D001427:Bacterial Toxins / Q000633:toxicity*; D018929:Cell Culture Techniques; D016360:Clostridioides difficile / Q000378:metabolism / Q000502:physiology*; D003106:Colon / Q000187:drug effects / Q000276:immunology*; D004768:Enterotoxins / Q000633:toxicity*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology*; D009924:Organ Culture Techniques
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile
keywords: C. difficile; adhesion; cell polarity; toxins