Enterohemorrhagic E. coli O157:H7 (EHEC) causes hemolytic uremic syndrome (HUS) via Shiga toxin. The molecular mechanism by which Shiga toxin (Stx) kills renal endothelial cells is:

• A Adenylyl cyclase activation leading to chloride secretion and fluid loss
• B Pore formation in the endothelial cell membrane causing oncotic lysis
• C Stimulation of NF-κB leading to excess TNF-α production by endothelial cells
• D Binding to Gb3 receptor (globotriaosylceramide) via B subunits, then A subunit N-glycosidase activity cleaves a specific adenine from 28S rRNA, halting protein synthesis ✓

Explanation

Shiga toxin (AB5 type) has five B subunits that bind Gb3 (globotriaosylceramide) receptors, which are highly expressed on renal glomerular endothelium and in the CNS. After endocytosis, the A subunit is cleaved to A1 + A2 fragments; A1 is an N-glycosidase that depurinates a specific adenine in the 28S rRNA of the 60S ribosomal subunit, irreversibly halting protein synthesis and triggering apoptosis. Gb3 expression is upregulated by TNF-α, explaining why antibiotics (promoting LPS release and TNF) may worsen HUS.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.