CLOSTRIDIUM-DIFFICILE TOXIN-B INDUCES APOPTOSIS IN INTESTINAL CULTURED-CELLS

Toxigenic strains of the anaerobic bacterium Clostridium difficile pro duce at least two large, single-chain protein exotoxins involved in th e pathogenesis of antibiotic-associated diarrhea and colitis. Toxin A (CdA) is a cytotoxic enterotoxin, while toxin B (CdB) is a more potent cytotoxin lacking enterotoxic activity. This study dealt with CdB, pr oviding the first evidence that intestinal cells exposed to this toxin exhibit typical features of apoptosis in that a significant proportio n of the treated cells displayed nuclear fragmentation and chromatin c ondensation. In keeping with ultrastructural data, CdB-treated cells s howed the typical flow cytometric hallmark of apoptosis consisting of a distinct sub-G, peak. The CdB-induced apoptotic response was dose an d time dependent and not simply due to the actin-disrupting effect of the toxin or to the subsequent impairment of cell anchorage. Rather, t he inhibition of proteins belonging to the Rho family due to CdB seems to play a role in the induction of apoptosis in intestinal cells. The origin of cells and the growth rate may also be cofactors relevant to such a response.