What mechanism does cholera toxin utilize to induce secretory diarrhea?

Cholera toxin induces secretory diarrhea primarily through the activation of the Gs protein via ADP-ribosylation. When cholera toxin enters the intestinal epithelial cells, it catalyzes the transfer of an ADP-ribose moiety to the Gs protein, which prevents the Gs protein from being inactivated. As a result, Gs remains in its active form, leading to prolonged activation of adenylate cyclase.

This persistent activation of adenylate cyclase then causes an excessive production of cyclic AMP (cAMP). Elevated cAMP levels stimulate the secretion of electrolytes and water into the intestinal lumen, resulting in the hallmark watery diarrhea associated with cholera. The diarrhea can lead to significant fluid loss and dehydration if not managed appropriately.

Understanding this mechanism highlights the importance of the cAMP signaling pathway in regulating fluid and electrolyte balance in the intestines and illustrates how bacterial toxins can exploit host cellular mechanisms to cause disease.