A neonate develops haemorrhagic enterocolitis and haemolytic uraemic syndrome (HUS) after consuming formula contaminated with E. coli O157:H7. The Shiga toxin (Stx) responsible for HUS acts by which mechanism?

• A Activates adenylate cyclase via ADP-ribosylation of Gs protein
• B N-glycosidase activity depurinating 28S rRNA, halting protein synthesis in renal endothelial cells ✓
• C Forms pores in the lipid bilayer of colonocytes
• D Cross-links IgA receptors on platelets causing aggregation

Explanation

Shiga toxin (Stx1/Stx2) is an AB5 toxin. The B pentamer binds globotriaosylceramide (Gb3) receptor on glomerular endothelial cells and enters via retrograde transport. The A subunit has RNA N-glycosidase (ribosome-inactivating protein, RIP) activity that depurinates a specific adenine in the 28S rRNA of the 60S ribosomal subunit, irreversibly halting eukaryotic protein synthesis and causing endothelial cell death, leading to the thrombotic microangiopathy of HUS. Adenylate cyclase activation is cholera toxin's mechanism (via ADP-ribosylation of Gs). Gb3 is highly expressed on renal endothelium, explaining kidney-specific injury.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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