A 20-year-old man presents with acute watery diarrhoea producing 'rice-water' stools during a cholera outbreak. Stool dark-field microscopy shows rapidly motile vibrios with 'shooting star' motility that are inhibited on addition of O1 antiserum. Culture on TCBS agar grows yellow colonies. What is the mechanism of cholera toxin?
- A A1 peptide ADP-ribosylates Gsα, permanently activating adenylyl cyclase; raises cAMP; activates CFTR chloride channels causing Cl⁻ and water secretion ✓
- B B subunit permanently activates Gs protein by ADP-ribosylation of adenylyl cyclase; A subunit binds GM1 ganglioside
- C Activates guanylyl cyclase increasing cGMP, inhibiting NaCl absorption
- D Binds to TLR4 causing pro-inflammatory IL-8 secretion and osmotic diarrhoea
Correct answer: A. A1 peptide ADP-ribosylates Gsα, permanently activating adenylyl cyclase; raises cAMP; activates CFTR chloride channels causing Cl⁻ and water secretion
Explanation
Cholera toxin (CT) is an AB5 toxin: five B subunits bind GM1 ganglioside on enterocytes, facilitating A subunit entry. The A1 peptide irreversibly ADP-ribosylates the α-subunit of Gs protein, permanently activating adenylyl cyclase, which raises intracellular cAMP. Elevated cAMP activates protein kinase A, which phosphorylates CFTR, causing massive Cl⁻ secretion and inhibiting NaCl absorption, resulting in isotonic water loss and characteristic rice-water stools. E. coli heat-stable toxin (STa) acts via cGMP, not cAMP.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.