A post-abdominal surgery patient develops sudden onset severe watery diarrhea with pseudomembranes seen on colonoscopy, following a course of broad-spectrum antibiotics. The toxin of the causative organism acts by:

• A Activating adenylate cyclase, increasing intracellular cAMP
• B Blocking acetylcholine release at neuromuscular junction
• C Glucosylating Rho GTPases, causing actin cytoskeleton disruption and cell death ✓
• D ADP-ribosylation of EF-2 inhibiting protein synthesis

Explanation

Clostridium difficile is the most common cause of antibiotic-associated pseudomembranous colitis. Toxin A (enterotoxin) and Toxin B (cytotoxin) both act by glucosylating Rho family GTPases (Rac1, RhoA, Cdc42), inactivating these regulators of actin cytoskeleton dynamics. This causes disruption of tight junctions, rounding of cells, cytoskeletal collapse, and ultimately epithelial cell death. Toxin B is more potent and is the primary virulence determinant. First-line treatment is oral vancomycin or fidaxomicin.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.