Vibrio cholerae are comma-shaped,gram-negative bacteria that have been the cause of seven great long-lasting epidemics (pandemics) of diarrheal disease. Many of these pandemics begin in the Ganges Velley of India and bangladesh, which is never free from cholera, and then move east. Although there are 140 serotypes of V.Cholerae, until recently only the 01 serotype was associated with severe diarrhea. Beginning in 1992 a new v. cholerae serotype (0139, also known as Bengal) has been associated with severe, watery diarrhea. Visit for

Pathogenesis. The vibrios never invade the epithelium but instead remain within the lumen and secrete enterotoxin, which is encoded by a virulence phage. Flagellar proteins involved in motility and attachment are necessary for efficient bacterial colonization as has been described for Compylobacter. ( This is is in contrast to Shigella species and certain E.coli strains which are nonmotile and yet invasive.) The Vibrio hemagglutinin, Which is a metalloprotease, is important for detachment of Vibrio from epithelial cells, analogous to the neuraminidase of influenza virus described earlier.

The secretory diarrehea characteristic of th disease is caused by release of an enterotoxin, called cholera toxin that is nearly identical to E.coli enterotoxin. Cholera toxin is composed of five binding peptides B and a catalytic peptide A. The peptides B bind to carbohydrates on GM ganglioside on the surface of epithelial cells of the small intestines. Within the cell the disulfide bond linking the two fragments of peptide. A (A1 and A2)is cleaved, and catalytic peptide A1 interacts with 20-KD cytosolic G proteins calld ADP-ribosylation factors. ADP-ribosylation factors and guanosine triphosphate (GTP) increase the activity of cholera toxin, which ADP- ribosylates a 49-KD G protein called G) that in turn stimulates adenylate cyclase ADP-ribosylated G is permanently is an active GTP-bound state resulting in persistent activation of adenylate cyclase, high levels of intracellular Camp, and massive secretion of chloride, sodium and water. Because the effects of cholera toxin are abrogated by tiny inhibitors of serotonin, the intestinal nervous system may also be involved in the action of the cholera toxin. ?The reabsorptive function of the large intestine is overwhelmed, and liters of dilute ?rice-water? diarrhea containing flecks of mucus but few leukocytes are produced. Because overall absorption in the gut remains intact, oral formulas can replace massive sodium, chloride and bicarbonate and fluid losses and reduce the mortality rate from 50% to less than 1%