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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
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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.
4.3
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