Toxins of Clostridium difficile

The virulence of Clostridium difficile is mediated by two members of the large clostridial cytotoxin family, toxin A (TcdA) and toxin B (TcdB). The genes, tcdA and tcdB, respectively, are located on a large pathogenicity locus (PALoc) in the bacterial chromosome. Toxin synthesis is regulated by an accessory gene regulator quorum-signaling system, mediated via a small thiolactone that can be detected in stools of patients with C. difficile infection (CDI). TcdA and TcdB consist of single, large polypeptide chains with folds stabilized by disulfide bonds. The toxin amino-termini are catalytic and are highly conserved, both function in the target cell cytoplasm by similar mechanisms. Certain strains of C. difficile have recently been associated with widespread epidemics and significantly increased morbidity and mortality attributed to hypervirulence. The most important step in toxin:cell interaction is receptor-mediated uptake of toxins.