What is the primary toxin responsible for profuse watery diarrhea in cholera and its cellular action?

• A. Shiga toxin; inhibits protein synthesis
• B. Diptheria toxin; inactivates elongation factor 2
• C. Cholera toxin; activates adenylate cyclase via ADP-ribosylation, increasing cAMP and causing chloride secretion
• D. Tetanus toxin; cleaves SNARE proteins

Answer: (C)

Cholera toxin is the toxin responsible for the profuse watery diarrhea seen in cholera. It acts by ADP-ribosylating the Gs alpha subunit of the stimulatory pathway that activates adenylyl cyclase, keeping it in an active state. This drives a sustained rise in cAMP inside enterocytes, which opens the CFTR chloride channel. The resulting chloride (and accompanying bicarbonate) secretion into the intestinal lumen draws water with it, producing the characteristic large volumes of watery stool.

Understanding this helps you see why this diarrhea is so watery and occurs with dehydration and electrolyte losses. Other toxins work through different targets and lead to different clinical pictures: Shiga toxin inhibits protein synthesis and can cause bloody diarrhea and HUS; diphtheria toxin also inhibits protein synthesis but via EF-2; tetanus toxin blocks neurotransmitter release and causes spastic paralysis.