A 3-year-old child develops haemolytic uraemic syndrome (HUS) 5 days after a bloody diarrhoeal illness. The causative E. coli produces a toxin that acts by which mechanism to cause endothelial damage?

• A Heat-labile toxin (LT) ADP-ribosylates Gs-alpha, causing persistent cAMP elevation and chloride hypersecretion
• B Shiga toxin (Stx) binds Gb3 receptor on endothelial cells, enters via endocytosis, and N-glycosidically cleaves the 28S rRNA at adenine 4324, inhibiting the 60S ribosomal subunit and halting protein synthesis ✓
• C Haemolysin A (HlyA) forms pores in glomerular endothelial cell membranes causing calcium influx
• D Cytotoxic necrotizing factor-1 (CNF1) deamidates Rho GTPases causing uncontrolled actin polymerization in endothelial cells

Explanation

HUS following bloody diarrhoea in children is caused by Shiga toxin-producing E. coli (STEC/EHEC), most commonly serotype O157:H7. Shiga toxin (Stx1 or Stx2) binds to the glycolipid receptor globotriaosylceramide (Gb3, also called CD77) on renal glomerular endothelial cells, is endocytosed via retrograde transport to the endoplasmic reticulum, where the A1 fragment depurinates a specific adenine residue (A4324) in 28S rRNA, irreversibly inactivating the 60S ribosome and causing cellular protein synthesis arrest and apoptosis. LT-I acts on adenylate cyclase in ETEC. HlyA is a separate virulence factor. CNF1 is produced by uropathogenic E. coli.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.