## Cholera Toxin: Structure and Function **Key Point:** Cholera toxin (CTX) is an AB5 enterotoxin that is the primary virulence factor responsible for the pathophysiology of cholera. ### Mechanism of Action 1. **ADP-ribosylation of Gs protein**: The A subunit of CTX catalyzes ADP-ribosylation of the α-subunit of the Gs (stimulatory G) protein in intestinal epithelial cells. 2. **Persistent cAMP elevation**: This modification locks Gs in the active (GTP-bound) state, leading to uncontrolled adenylate cyclase activation and sustained elevation of intracellular cAMP. 3. **Ion secretion**: Elevated cAMP activates protein kinase A (PKA), which phosphorylates cystic fibrosis transmembrane conductance regulator (CFTR) channels, causing massive secretion of Cl^−^ and Na^+^ into the intestinal lumen. 4. **Osmotic diarrhea**: Water follows the electrolytes osmotically, resulting in the characteristic **rice-water stools** (clear, watery, electrolyte-rich fluid without blood or mucus). ### Structural Features | Feature | Detail | |---------|--------| | **Type** | AB5 enterotoxin | | **A subunit** | Catalytic; contains ADP-ribosyltransferase activity | | **B subunit** | Pentameric; binds to GM1 ganglioside on intestinal epithelium | | **Chromosomal location** | Encoded by ctxAB genes in the CTX prophage | | **Heat stability** | Heat-labile (destroyed at >65°C) | **High-Yield:** CTX is the **only toxin** that causes the pathognomonic rice-water diarrhea. The mechanism is **not cytotoxic** (no cell death) but rather a functional derangement of ion transport. **Clinical Pearl:** The rice-water appearance is so characteristic that it is virtually diagnostic of cholera in endemic areas. The stool contains no blood, mucus, or inflammatory cells—it is purely a secretory diarrhea. **Mnemonic:** **CTX = cAMP-driven Transport eXcretion** — remember that cholera toxin works by locking the cAMP pathway in the "on" position.
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