Repetitive domain of Clostridium difficile toxin B exhibits cytotoxic effects on human intestinal epithelial cells and decreases epithelial barrier function

We have used recombinant repetitive domain of Clostridium difficile toxin B obtained from two different strains, rec-TcdB310463 and rec-TcdB38864 and a model intestinal epithelial cell line(s) to characterize their cytotoxic and cytopathic effect and influence on tight-junction organization. Both recombinant receptor binding domains caused intestinal epithelial cell damage, decreased transepithelial electrical resistance and induced translocation of ZO-1 from tight-junction proteins although less efficiently as holotoxins. Recombinant repetitive TcdB domains also caused stimulation of interleukin IL-8 synthesis in HT-29 cells.This is the first description of glucosyltransferase independent toxicity of TcdB and these C-terminal mediated effects may contribute to the pathophysiology of C. difficile infection.