A child in Bihar develops profuse watery rice-water stools with no fecal leucocytes. Vibrio cholerae O1 El Tor biotype is isolated. Which toxin mechanism accounts for the profuse secretory diarrhoea?
- A Cholera toxin B subunit directly activates adenylyl cyclase, raising cAMP
- B Cholera toxin A subunit ADP-ribosylates the stimulatory G protein (Gs-alpha), constitutively activating adenylyl cyclase, leading to massive chloride and water secretion into the intestinal lumen ✓
- C Cholera toxin activates guanylyl cyclase, raising cGMP and inhibiting Na+/H+ exchange
- D Zot (Zonula occludens toxin) disrupts tight junctions causing osmotic secretion
Explanation
Cholera toxin (CT) consists of 1A and 5B subunits. The B pentamer binds GM1 ganglioside on enterocytes; the A1 fragment enters the cell and catalyses ADP-ribosylation of the alpha subunit of Gs protein, locking it in the active (GTP-bound) state and constitutively activating adenylyl cyclase. The resultant massive rise in intracellular cAMP activates CFTR chloride channels (and inhibits coupled NaCl absorption), causing profuse secretion of chloride and water — up to 20 L/day. Heat-stable E. coli toxin (STa) acts via cGMP/guanylyl cyclase. Zot increases intestinal permeability but is not the primary mechanism.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
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Written and medically reviewed by the StethoPrep medical team.