Today’s question will test your knowledge of an often-tested, high-yield USMLE Step 1 microbiology/pharmacology concept. The question is followed by a breakdown of the answer choices and a detailed explanation of the correct answer. Click the ♥️ when you’re done!
A 40-year-old female presents to the clinic with severe left leg pain several hours after cutting herself while raking leaves in her backyard. She has a temperature of 101.1°F and a heart rate of 110 beats/min. Examination of the left lower extremity reveals a small laceration on the ankle with an overlying bulla extending to the posterior thigh. Palpation of the skin is notable for crepitus. Surgical investigation reveals necrosis of the soleus muscle. Tissue culture reveals a gram-positive, anaerobic, spore-forming bacillus. Which of the following most accurately describes the mechanism of cellular damage caused by this organism?
A. Inhibition of protein synthesis by ribosomal inactivation
B. Disruption of cell membranes by phospholipase activity
C. Inhibition of neurotransmitter release by blocking synaptic vesicle fusion
D. Induction of apoptosis through caspase activation
E. Disruption of the cytoskeleton by actin depolymerization
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ANSWER + QUESTION BREAKDOWN
The Mental Model for this week’s question:
Step 1. Identify the causative organism.
Step 2. Ask yourself the MOA of the organism’s ability to cause cellular damage.
Step 3. Look for your answer in the answer choices.
GENERAL ANALYSIS
A 40-year-old female presents with severe pain, crepitus, and necrosis. The symptoms started shortly after cutting herself in the backyard. Microscopy is positive for a gram-positive, anaerobic, spore-forming bacillus.
ANSWER CHOICES:
ANSWER CHOICE A: Inhibition of protein synthesis by ribosomal inactivation
This mechanism is characteristic of toxins like diphtheria toxin and Shiga toxin, which inhibit protein synthesis by inactivating ribosomes.
ANSWER CHOICE B: Disruption of cell membranes by phospholipase activity
Clostridium perfringens produces alpha-toxin (phospholipase C), which hydrolyzes phospholipids in cell membranes, leading to cell lysis and tissue necrosis.
ANSWER CHOICE C: Inhibition of neurotransmitter release by blocking synaptic vesicle fusion
This mechanism is characteristic of botulinum toxin, which inhibits acetylcholine release at neuromuscular junctions.
ANSWER CHOICE D: Induction of apoptosis through caspase activation
Some bacterial toxins can induce apoptosis through caspase activation, leading to programmed cell death.
ANSWER CHOICE E: Disruption of the cytoskeleton by actin depolymerization
Some bacterial toxins, such as those produced by Clostridium difficile, disrupt the cytoskeleton by depolymerizing actin.
FINAL VERDICT…
Clostridium perfringens is a gram-positive, anaerobic, spore-forming bacillus known for causing gas gangrene (clostridial myonecrosis). The primary virulence factor of Clostridium perfringens is alpha toxin, which is a phospholipase C enzyme. This toxin hydrolyzes phospholipids in the cell membranes, leading to cell lysis, tissue necrosis, and gas production.
The alpha toxin's phospholipase activity disrupts the integrity of cell membranes, causing extensive tissue damage and contributing to the rapid spread of infection.
The clinical presentation of severe pain, crepitus, and necrosis, along with the identification of a gram-positive, anaerobic, spore-forming bacillus, is consistent with Clostridium perfringens infection.
The mechanism of cellular damage caused by this organism is best described by the disruption of cell membranes through phospholipase activity, making option B the correct answer.
FINAL ANSWER: B: Disruption of cell membranes by phospholipase activity
That’s it for today’s question!
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