Microbes and microbial Toxins: paradigms for microbial-mucosal toxins. V. Cholera: invasion of the intestinal epithelial barrier by a stably folded protein toxin.

Cholera toxin (CT) produced by Vibrio cholerae is the virulence factor responsible for the massive secretory diarrhea seen in Asiatic cholera. To cause disease, CT enters the intestinal epithelial cell as a stably folded protein by co-opting a lipid-based membrane receptor, ganglioside G(M1). G(M1) sorts the toxin into lipid rafts and a retrograde trafficking pathway to the endoplasmic reticulum, where the toxin unfolds and transfers its enzymatic subunit to the cytosol, probably by dislocation through the translocon sec61p. The molecular determinants that drive entry of CT into this pathway are encoded entirely within the structure of the protein toxin itself.