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Review Question - QID 108945

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QID 108945 (Type "108945" in App Search)
A 61-year-old male presents to the emergency department complaining of malaise. He reports a two-day history of rapidly progressive fatigue, malaise, fever, and dyspnea. The patient immigrated from Finland five years ago and works on a large farm. His past medical history is notable for diabetes mellitus and emphysema. He takes metformin, salmeterol, and tiotropium. He has a 40 pack-year smoking history. His temperature is 102.3°F (39.1°C), blood pressure is 90/50 mmHg, pulse is 130/min, respirations are 30/min, and oxygen saturation is 92% on room air. Physical examination is notable for rales at the bilateral lung bases. Chest radiography reveals a widened mediastinum and bilateral pulmonary infiltrates. He is subsequently admitted and started on broad-spectrum antibiotics and fluid resuscitation. However, his fever rapidly progresses and he perishes the following day. Results from a blood culture taken on admission are shown in Figure A. The pathogen responsible for this patient’s condition produces a toxin with which of the following mechanisms of action?
  • A

Directly activates adenylyl cyclase

26%

136/532

Mimics adenylyl cyclase

37%

195/532

Inhibits 60S ribosomal subunit

9%

49/532

Binds Fc portion of immunoglobulin

11%

56/532

Depolymerizes actin cytoskeleton

13%

69/532

  • A

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The patient in this vignette presents with rapidly progressive pulmonary disease suggestive of pulmonary anthrax. This condition is caused by Bacillus anthracis, a gram-positive rod that produces edema factor which mimics the activity of adenylyl cyclase.

Pulmonary anthrax is caused by inhalation of the bacterial spores and presents with rapidly progressive fever, pulmonary hemorrhage, mediastinitis, shock, and death. Bacillus anthracis is often tested in the context of close contact with infected animals (typically in sheep or goat farmers) or as a form of bioterrorism affecting postal workers. Bacillus anthracis produces a toxin (edema factor) that mimics the activity of adenylyl cyclase by increasing cAMP production – this is responsible for the edematous borders seen in cutaneous anthrax.

Figure A demonstrates the characteristic appearance of Bacillus anthracis, a gram-positive spore-forming rod that is sometimes described as “boxcar-like” or “serpentine.” Bacillus anthracis is the only bacterium with a polypeptide D-glutamate capsule. Although the bacteria are gram-positive (purple), their spores often appear pink on Gram stain.

Incorrect Answers:
Answer 1: Enterotoxigenic E. coli (ETEC) and Vibrio cholerae both produce toxins that stimulate adenylyl cyclase via ADP-ribosylation of an associated G-protein. This leads to a buildup of intracellular cAMP, thereby promoting water loss from the gut.

Answer 3: Shigella dysenteriae produces the Shiga toxin, an enterotoxin that inhibits the 60S ribosomal subunit. This impairs protein synthesis in enterocytes, leading to cell death and a syndrome of bloody diarrhea.

Answer 4: Staphylococcus aureus produces protein A, an exotoxin that binds the Fc portion of immunoglobulin molecules to block opsonization and phagocytosis. S. aureus also produces several other toxins including exfoliatin (destroys intra-epidermal desmosomes to cause staphylococcal scalded skin syndrome) and TSST-1 superantigen (binds MHC II and the T cell receptor to cause toxic shock syndrome).

Answer 5: Clostridium difficile produces toxin B, a cytotoxin that disrupts the actin cytoskeleton of enterocytes. This leads to rapid interference with normal cell morphology and functions, eventually causing cell death. This bacterium also produces toxin A, a pro-inflammatory enterotoxin that disrupts the normal gut mucosa.

Bullet Summary:
Bacillus anthracis is a gram-positive rod with a large D-glutamate capsule that produces a toxin that functions as a bacterial adenylyl cyclase. Inhalation of bacterial spores causes pulmonary anthrax, a deadly condition characterized by severe fever, pulmonary hemorrhage, mediastinitis, and shock.

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