Bit · Micro
Exotoxin Syndromes — Cholera, Diphtheria, Tetanus, Botulism, C. difficile, ETEC
Six classic bacterial exotoxin syndromes. Each toxin has a specific mechanism, a specific cell or signal it hijacks, and a specific clinical syndrome.
Mechanism
Bacterial exotoxins are secreted proteins, each with a precise molecular target. Most have an AB structure (B = binds, A = acts). The clinical syndrome falls directly out of which signal is being broken:
- Vibrio cholerae — cholera toxin. ADP-ribosylates Gs → permanent activation of adenylate cyclase in intestinal epithelium → ↑↑ cAMP → massive efflux of Cl⁻ and water → rice-water diarrhea, severe dehydration. Treat: oral rehydration.
- Enterotoxigenic E. coli (ETEC) — heat-labile toxin (LT) does the same trick as cholera (↑ cAMP). Heat-stable toxin (ST) increases cGMP. Watery 'traveler's diarrhea.'
- Corynebacterium diphtheriae — diphtheria toxin. ADP-ribosylates EF-2 → halts protein synthesis. Pseudomembranous pharyngitis (gray-white adherent membrane), myocarditis, neurologic. Toxin gene on lysogenic phage. Treat: antitoxin + erythromycin/penicillin.
- Clostridium tetani — tetanospasmin. Cleaves SNAREs in inhibitory interneurons (Renshaw cells) of the spinal cord → blocks release of GABA and glycine → unopposed motor neuron firing → spastic paralysis. Lockjaw (trismus), risus sardonicus, opisthotonos. Treat: antitoxin + metronidazole + wound care; tetanus toxoid (vaccine) for prevention.
- Clostridium botulinum — botulinum toxin. Cleaves SNAREs at presynaptic terminal of cholinergic neurons → blocks ACh release at neuromuscular junction → flaccid paralysis. Descending paralysis: ptosis, diplopia, dysphagia, dysphonia, respiratory failure. Infants: 'floppy baby' (honey-related). Treat: antitoxin; supportive (intubation).
- Clostridioides difficile — toxin A (enterotoxin) + toxin B (cytotoxin). Disrupts colonic epithelium → pseudomembranous colitis. Follows broad-spectrum antibiotics (especially clindamycin, fluoroquinolones, cephalosporins). Treat: oral vancomycin or fidaxomicin; fecal transplant for recurrent.
- Staphylococcus aureus TSST-1 — superantigen (binds MHC II and TCR non-specifically → polyclonal T-cell activation → cytokine storm). Toxic shock syndrome — fever, rash, hypotension, multi-organ involvement. Historical link: tampons. Treat: removal of source, anti-staph antibiotics.
- Streptococcus pyogenes (GAS) exotoxins — scarlet fever (erythrogenic toxin); streptococcal TSS (superantigens, similar to staph TSST-1).
Differentiator Table
| Toxin / organism | Molecular target | Mechanism | Clinical syndrome |
|---|---|---|---|
| Cholera toxin (V. cholerae) | Gs protein in gut enterocyte | ADP-ribosylates Gs → ↑↑ cAMP | Rice-water diarrhea, severe dehydration |
| LT (ETEC E. coli) | Gs (gut) | ↑ cAMP (same as cholera) | Watery traveler's diarrhea |
| ST (ETEC) | Guanylyl cyclase | ↑ cGMP | Watery diarrhea |
| Diphtheria toxin | EF-2 (elongation factor) | ADP-ribosylates EF-2 → halts protein synthesis | Pseudomembranous pharyngitis, myocarditis |
| Tetanospasmin (C. tetani) | SNAREs in inhibitory spinal interneurons | Blocks GABA / glycine release | SPASTIC paralysis (lockjaw, opisthotonos) |
| Botulinum toxin (C. botulinum) | SNAREs at presynaptic cholinergic terminal | Blocks ACh release at NMJ | FLACCID descending paralysis |
| C. difficile toxin A / B | Colonic epithelial cells | Disrupts cytoskeleton → epithelial injury | Pseudomembranous colitis after antibiotics |
| TSST-1 (S. aureus) | MHC II + TCR | Superantigen → cytokine storm | Toxic shock syndrome |
| Streptolysin O (S. pyogenes) | Cell membranes | Pore-former; antigenic (ASO titer) | Rheumatic fever follow-up marker |
| Erythrogenic toxin (S. pyogenes) | Endothelium | Toxin-mediated rash | Scarlet fever |
| Anthrax toxin (B. anthracis) | Lethal factor (MAPKK), edema factor (adenylate cyclase) | Tissue necrosis + edema | Cutaneous anthrax (eschar), inhalational anthrax |
The Pivot
Pattern-match the syndrome to the toxin:
- Watery massive diarrhea → cholera toxin (or ETEC LT) → cAMP up.
- Pseudomembrane in throat + cardiac + neuro → diphtheria toxin → EF-2 halted.
- Spastic paralysis (lockjaw, opisthotonos) → tetanospasmin → inhibitory interneuron SNAREs cleaved.
- Flaccid descending paralysis → botulinum toxin → presynaptic ACh blocked.
- Pseudomembranous colitis after antibiotics → C. difficile toxins A/B.
- Fever + rash + hypotension + tampon or wound → TSST-1 superantigen.
NBME-Style Stem
A previously healthy 24-year-old man develops symmetric descending weakness 18 hours after eating home-canned green beans. He has bilateral ptosis, diplopia, dysphagia, and dry mouth. Strength is decreased in proximal upper extremities and progressing to lower extremities. Sensation is intact. Which of the following best describes the mechanism of his disease?
Concept Anchor
Each exotoxin hijacks one specific signal — cholera locks Gs, diphtheria stops protein synthesis, tetanus cleaves inhibitory SNAREs, botulinum cleaves motor SNAREs, C. difficile poisons the colon, TSST-1 jams MHC/TCR. The syndrome you see is the molecular target you can name.