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