A post-operative patient develops severe watery diarrhoea after a course of clindamycin. Stool toxin assay is positive for toxin A and toxin B. Regarding the pathogenesis of Clostridioides difficile, toxin B (cytotoxin):
- A Is an ADP-ribosyltransferase that inactivates Gi proteins causing sustained cAMP elevation
- B Is a metalloprotease that cleaves occludin in the tight junction complex
- C Is a glucosyltransferase that inactivates Rho GTPases (RhoA, Rac1, Cdc42), disrupting actin cytoskeleton and tight junctions ✓
- D Is an ADP-ribosyltransferase that inactivates G-actin causing neutrophil paralysis
Explanation
C. difficile toxin B (TcdB) is a large glucosyltransferase (270 kDa) that enters colonocytes and glucosylates the Rho family GTPases (RhoA, Rac1, Cdc42) at threonine-37 using UDP-glucose as cofactor. This inactivates Rho GTPases, causing depolymerization of the actin cytoskeleton, loss of tight junctions, cell rounding, and apoptosis — manifesting as pseudomembranous colitis. Toxin A (TcdA) also glucosylates Rho GTPases but primarily causes fluid secretion and neutrophil recruitment. C. difficile binary toxin (CDT) is an ADP-ribosyltransferase that acts on actin, but is distinct from toxin B.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.