USMLE Step 1 Microbiology Questions: Infectious Diarrhea – C. difficile, EHEC and Cholera

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Diarrhea-causing organisms appear on almost every USMLE Step 1 exam. The questions usually test the exposure clue, the toxin mechanism or a lab feature of the organism. Here are three practice questions. Pick your answer first, then open the explanation.

Question 1: Watery diarrhea after antibiotics in the hospital

A 72-year-old woman is hospitalized for pneumonia and treated with ceftriaxone. On day 6 she develops frequent watery diarrhea, abdominal cramps and a fever of 38.4°C (101.1°F). Her leukocyte count is 21,000/mm³. Colonoscopy shows multiple yellow-white plaques on the colonic mucosa. The major toxins of the causative organism act by which of the following mechanisms?

A. ADP-ribosylation of Gs, increasing cAMP
B. Inactivation of the 60S ribosomal subunit
C. Activation of guanylate cyclase, increasing cGMP
D. Glucosylation of Rho-family GTPases, disrupting the actin cytoskeleton
E. ADP-ribosylation of Gi, preventing its inhibition of adenylate cyclase

Correct answer: D. Glucosylation of Rho-family GTPases, disrupting the actin cytoskeleton

This is Clostridioides difficile colitis after antibiotic use, with pseudomembranes seen on colonoscopy. C. difficile produces toxin A (enterotoxin) and toxin B (cytotoxin). Both glucosylate Rho-family GTPases, which disrupts the actin cytoskeleton, breaks down tight junctions and kills colonic cells. Diagnosis is by stool PCR or toxin testing; first-line treatment is oral fidaxomicin or vancomycin.

Why the other options are wrong:

  • ADP-ribosylation of Gs is the mechanism of cholera toxin and ETEC heat-labile toxin.
  • 60S ribosome inactivation is the mechanism of Shiga toxin and Shiga-like toxin (EHEC).
  • Increased cGMP is caused by the heat-stable toxin of ETEC.
  • ADP-ribosylation of Gi is the mechanism of pertussis toxin.

Question 2: Bloody diarrhea after a hamburger, then kidney failure

A 7-year-old girl develops abdominal cramps and bloody diarrhea 3 days after eating an undercooked hamburger at a picnic. She has no fever. Six days later she is pale and has decreased urine output. Laboratory studies show hemoglobin 7.8 g/dL, platelets 42,000/mm³, an elevated serum creatinine and schistocytes on the peripheral blood smear. Which of the following is a characteristic laboratory feature of the most likely causative organism?

A. Oxidase-positive, comma-shaped rod that grows in alkaline media
B. Does not ferment sorbitol
C. Grows at 42°C under microaerophilic conditions
D. Produces hydrogen sulfide and does not ferment lactose
E. Grows best after cold enrichment at 4°C

Correct answer: B. Does not ferment sorbitol

This child has hemolytic uremic syndrome (microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury) after bloody diarrhea from undercooked beef. The cause is enterohemorrhagic E. coli (EHEC) O157:H7. Unlike most E. coli, O157:H7 does not ferment sorbitol, which helps identify it on sorbitol MacConkey agar. Its Shiga-like toxin inactivates the 60S ribosome and damages the endothelium. Antibiotics are generally avoided because they may increase toxin release.

Why the other options are wrong:

  • Oxidase-positive comma-shaped rods in alkaline media describes Vibrio cholerae.
  • Growth at 42°C, microaerophilic describes Campylobacter jejuni.
  • H2S production, lactose nonfermenter describes Salmonella.
  • Cold enrichment describes Yersinia enterocolitica.

Question 3: Profuse “rice-water” stools after travel

A 30-year-old aid worker returns from a region with a recent flood and develops sudden, painless, profuse watery diarrhea that looks like rice water. He has no fever. He is lethargic, with dry mucous membranes and a blood pressure of 88/56 mm Hg. Which of the following best explains the mechanism of his diarrhea?

A. Bacterial invasion of colonic mucosa causing ulceration
B. Toxin-mediated inactivation of the 60S ribosomal subunit
C. Osmotic diarrhea from lactase deficiency
D. Glucosylation of Rho-family GTPases
E. Toxin-mediated ADP-ribosylation of Gs, increasing cAMP and chloride secretion

Correct answer: E. Toxin-mediated ADP-ribosylation of Gs, increasing cAMP and chloride secretion

Cholera toxin from Vibrio cholerae permanently activates Gs by ADP-ribosylation. This increases cAMP, which drives chloride secretion through CFTR, with water following into the bowel lumen. The result is massive secretory, “rice-water” diarrhea without inflammation, which can quickly cause severe dehydration. The mainstay of treatment is rehydration (oral rehydration solution, or IV fluids if severe).

Why the other options are wrong:

  • Mucosal invasion (e.g., Shigella) causes bloody diarrhea with fever.
  • 60S ribosome inactivation is the action of Shiga toxin.
  • Lactase deficiency causes bloating and diarrhea after dairy, not profuse diarrhea and shock.
  • Rho GTPase glucosylation is the action of C. difficile toxins.

Key takeaways

  • C. difficile toxins A and B glucosylate Rho GTPases; treat with oral fidaxomicin or vancomycin.
  • EHEC O157:H7 does not ferment sorbitol and can cause hemolytic uremic syndrome.
  • Cholera toxin ADP-ribosylates Gs, raising cAMP; the treatment is rehydration.

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Written and reviewed by Dr. Ray Makar, MD, dermatologist with 20 years of clinical practice. Last reviewed: October 2026. For exam preparation only, not medical advice.

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