Cholera Toxin Mechanism: How Vibrio cholerae Causes Profuse Diarrhea

Cholera toxin (CT) and heat-labile toxin (LT) from Vibrio cholerae hijack intestinal epithelial signaling, causing massive secretory diarrhea.

Molecular Mechanism

1. Binding: CT B-subunit pentamer binds GM1 ganglioside on enterocyte apical membrane.
2. Internalization: A-subunit (ADP-ribosyltransferase) enters cytosol.
3. ADP-ribosylation: A1 moiety modifies Gsα protein → locks it in GTP-bound active state.
4. cAMP surge: Constitutive adenylate cyclase activation → ↑ intracellular cAMP.
5. CFTR activation: cAMP opens cystic fibrosis transmembrane conductance regulator (CFTR) Cl⁻ channel.
6. Secretion: Cl⁻ efflux → Na⁺ & water follow paracellularly → isotonic fluid floods lumen.

Clinical Correlates

• "Rice-water" stool: mucus flecks in watery fluid.
• Rapid dehydration, hypokalemia, metabolic acidosis.
• ORT (oral rehydration therapy) with glucose-electrolyte solution exploits SGLT1 cotransport (glucose enhances Na⁺/water absorption) — lifesaving.

Other Virulence Factors

Toxin-coregulated pilus (TCP) for colonization; biofilm formation; accessory toxins (hemolysin, enterotoxin).