Vibrio cholerae O1 El Tor biotype produces cholera toxin. Which intracellular signaling mechanism produces the profuse watery diarrhea?

• A CT activates phospholipase C → IP3 → intracellular Ca2+ release → Cl− secretion
• B CT ADP-ribosylates Giα → adenylate cyclase disinhibition → cAMP rise
• C CT activates guanylate cyclase directly → cGMP-mediated Cl− secretion
• D CT B subunit binds GM1 ganglioside; CT A subunit ADP-ribosylates Gsα, locking adenylate cyclase in active state → cAMP accumulation → CFTR activation → massive Cl− secretion ✓

Explanation

Cholera toxin (CT) is an AB5 toxin. The B pentamer binds to GM1 ganglioside on enterocyte apical membrane. The A1 fragment (after reduction of A1-A2 subunits) ADP-ribosylates the alpha subunit of the stimulatory G protein (Gsα) at arginine 201, locking it in the GTP-bound active state, permanently activating adenylate cyclase, and leading to massive cAMP accumulation. Elevated cAMP activates CFTR chloride channels and inhibits NaCl absorption at villus tips → isotonic fluid secretion → rice-water diarrhea (up to 20 L/day). Heat-labile toxin (LT) of E. coli uses the identical mechanism.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.