Vibrio cholerae cholera toxin (CT) causes severe watery diarrhoea by acting on small intestinal epithelial cells. Its A1 subunit irreversibly ADP-ribosylates which target, and what is the downstream consequence?
- A Gs-alpha protein — locking it in an active GTP-bound state, persistently activating adenylate cyclase, raising intracellular cAMP and activating CFTR chloride channels ✓
- B Gi-alpha protein — inhibiting adenylate cyclase and causing hypersecretion of chloride
- C Rho GTPase — disrupting cytoskeleton and tight junctions allowing paracellular water loss
- D EF-2 (elongation factor 2) — inhibiting protein synthesis in enterocytes causing apoptosis
Explanation
Cholera toxin B pentamer binds GM1 ganglioside on enterocyte membranes and the A1 subunit is endocytosed and translocated to the cytoplasm, where it ADP-ribosylates the alpha subunit of Gs (stimulatory G protein) at Arg201, locking Gs-alpha in the active GTP-bound conformation. This persistently activates adenylate cyclase, massively elevating intracellular cAMP, which activates protein kinase A to phosphorylate CFTR (cystic fibrosis transmembrane conductance regulator) — causing continuous chloride secretion into the intestinal lumen, with sodium and water following passively, resulting in profuse 'rice-water' stools. Gi-alpha is ADP-ribosylated by pertussis toxin. EF-2 is ADP-ribosylated by diphtheria toxin/Pseudomonas exotoxin A.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.