A 55-year-old man treated with broad-spectrum clindamycin for cellulitis develops watery, foul-smelling diarrhea, abdominal cramping, and leukocytosis. Colonoscopy reveals yellowish-white pseudomembranes. What is the mechanism of action of the toxins produced by the causative organism?

Answer and explanation

Correct answer: D. Disruption of cytoskeleton integrity via actin depolymerization (Clostridioides difficile Toxins A & B)

  1. Step 1: Identify the condition: pseudomembranous colitis following antibiotic use (clindamycin) is caused by Clostridioides difficile superinfection.
  2. Step 2: C. difficile produces two major exotoxins: Toxin A (enterotoxin) and Toxin B (cytotoxin). Both act as glucosyltransferases that inactivate Rho-family GTPases (Rho, Rac, Cdc42). Inactivation disrupts actin microfilaments, leading to depolymerization of the actin cytoskeleton, breakdown of tight junctions, mucosal necrosis, and pseudomembrane formation.
Answer
Disruption of cytoskeleton integrity via actin depolymerization (Clostridioides difficile Toxins A & B).
Why not the others: Inhibition of protein synthesis by ADP-ribosylation of EF-2 is the mechanism of diphtheria toxin (Corynebacterium diphtheriae) and exotoxin A (Pseudomonas aeruginosa); Activation of adenylate cyclase via Gs protein ADP-ribosylation describes cholera toxin (Vibrio cholerae) and heat-labile enterotoxin (ETEC); Cleavage of SNARE proteins inhibiting glycine release is the mechanism of tetanospasmin (Clostridium tetani).

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