Clostridium difficile

virulence factors

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    The two large toxins A and B are thought to be the primary virulence factors of C. difficile. These toxins are encoded by two separate genes, named tcdA and tcdB. Together with three additional genes they form a 19.6-kb pathogenicity locus called PaLoc . TcdA and TcdB both disrupt the actin cytoskeleton of intestinal epithelial cells by the UDP-glucose-dependent glucosylation of proteins from the Rho and Ras subfamilies Some strains of C. difficile also produce an actin-specific ADP-ribosyltransferase called. The binary toxin CDT is unrelated to the well-characterized toxins TcdA and TcdB. It belongs to the group of clostridial binary toxins, which include the iota toxin of Clostridium perfringens type E, the toxin of Clostridium spiroforme, and the C2 toxin of Clostridium botulinum C and D.

     Binary toxins consist of two independent unlinked protein chains, designated CDTa (enzymatic component) and CDTb (binding component) in C. difficile. The binding component recognizes a cell surface receptor, resulting in the internalization of the enzymatic component into the cytosol, which catalyzes the ADP-ribosylation of monomeric actin and leads to disorganization of the cytoskeleton.

     The changes observed in cells include the rounding and depolymerization of actin filaments, and are similar to those induced by the C. spiroforme toxin. The cytotoxic effect of the CDT is neutralized by anti-Ib antibodies directed against the iota toxin of C. perfringens

     Since the majority of strains isolated from symptomatic patients produce only TcdA and TcdB, one can conclude that CDT is not required for the virulence of C. difficile, but it may serve as an additional virulence factor and may function in synergy with the large clostridial cytotoxins