Clostridium difficile toxins facilitate bacterial colonization by modulating the fence and gate function of colonic epithelium. J Infect Dis 209:1095–1104. http://dx.doi .org/10.1093/infdis/jit617

The contribution of Clostridium difficile toxin A and B (TcdA and TcdB) to cellular intoxication has been stud-ied 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 po-larity 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 con-text, 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 opportu-nistic pathogen to gain access to BL receptors, leading to a successful colonization of the colonic mucosa. Keywords. C. difficile; toxins; cell polarity; adhesion. The mucosal surface of the human body represents a first line of defense from the environment and external pathogens. This barrier is mainly composed by polar-ized epithelial cells with distinct apical (AP) and baso