Toxin-mediated diarrhoea: cholera and E. coli
- Mechanism
Cholera toxin switches intestinal cells into constant salt-and-water pumps; different E. coli strains cause diarrhoea in five distinct ways.
What it is
Vibrio cholerae stays in the lumen and never invades, yet it can kill within hours through massive secretory diarrhoea. Its toxin, carried on a phage, has one A and five B subunits; the B subunits bind GM1 ganglioside and the toxin travels backwards to the endoplasmic reticulum, from where the A fragment reaches the cytosol and locks the stimulatory G protein in its active state. E. coli pathotypes use similar or different tricks, which explains their different clinical pictures.
Step by step
- Cholera toxin B subunits bind GM1 ganglioside on enterocytes.
- The toxin travels by retrograde transport to the endoplasmic reticulum.
- The A fragment enters the cytosol and, with ADP-ribosylation factors, permanently activates Gsα.
- Adenylate cyclase raises cAMP, opening CFTR chloride channels.
- Chloride, bicarbonate and sodium accumulate in the lumen; water follows: litres of isotonic stool.
The E. coli pathotypes
| Pathotype | How it causes disease | Disease | Who |
|---|---|---|---|
| ETEC (enterotoxigenic) | Heat-labile toxin (cAMP) and heat-stable toxin (cGMP); no invasion | Watery travellers' diarrhoea | Travellers, young children in poor settings |
| EPEC (enteropathogenic) | Attaching and effacing lesions that flatten microvilli | Watery diarrhoea, outbreaks | Children under two |
| EHEC (enterohaemorrhagic) | Shiga-like toxin | Bloody diarrhoea, haemolytic uraemic syndrome | All ages; children at highest HUS risk |
| EIEC (enteroinvasive) | Invades epithelium like Shigella; no toxin | Acute self-limited colitis | Young children in poor settings |
| EAEC (enteroaggregative) | Adherence fimbriae and dispersin; aggregates on cells | Non-bloody, sometimes prolonged diarrhoea | Children, travellers, immunodeficient |
Clinical notes
- Oral rehydration solution uses sodium–glucose cotransport, which cholera toxin does not block.
- Vaccination during outbreaks and clean water are the main public-health controls.
Test yourself
Think of the answer, then tap the question to see it.
How does cholera toxin cause diarrhoea?
It ADP-ribosylates Gsα, keeping adenylate cyclase active; high cAMP opens CFTR, chloride is secreted and water follows.
Why are biopsies almost normal in cholera?
The organism stays in the lumen and acts through a toxin, without invading or destroying the mucosa.
Which E. coli pathotype causes haemolytic uraemic syndrome?
Enterohaemorrhagic E. coli (such as O157:H7), through Shiga-like toxin.
Which E. coli pathotype is the main cause of travellers' diarrhoea?
Enterotoxigenic E. coli (ETEC).
Elsewhere in DurgiPedia
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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Cholera (World Health Organization, 2024); About Escherichia coli Infection (Centers for Disease Control and Prevention, 2024).
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Representative model, for educational purposes only.