ABSTRACT
Vibrio cholerae causes severe and life-threatening diarrhea in humans. The onset of the disease is often rapid, and as much as a liter of fluid may be purged each hour, leading to massive dehydration and death. Many of the aspects of the pathogenesis of V. cholerae have been elucidated. The bacteria adhere to epithelial cells of the proximal small intestine and elaborate a potent enterotoxin, cholera toxin (CT). CT is composed of five B subunits, which bind the holotoxin to the GM1 ganglioside receptor of intestinal mucosa, and one A subunit, which stimulates the production of intracellular cAMP, ultimately leading to copious secretion of fluid into the intestinal lumen (reviewed by Holmes et al., Chapter 10). Although CT is the major toxin elicited by V. cholerae and is responsible for the massive purging in cholera patients, V. cholerae strains specifically deleted for genes encoding CT (Dctx), are still able to cause mild to moderate diarrhea and additional clinical
manifestations. Two additional toxins elaborated by V. cholerae are the zonula occludens toxin (Zot) and the accessory cholera enterotoxin (Ace). Zot increases the permeability of rabbit ileal tissue by altering the intercellular tight junctions. Ace acts as a classical enterotoxin, causing fluid secretion in the rabbit ligated ileal loop model and net ion secretion in the Ussing chamber (Trucksis et al., 1993). Although the mechanism of action of Ace has not yet been detailed, the predicted secondary structure and amino acid homology with other proteins suggests that it may act on the eukaryotic membrane as a pore-forming toxin.
