THE USMLE TIMES - #93
Hi there 👋
Welcome to issue #93 of The USMLE Times… This is the 93rd straight week we’ve posted our USMLE Times Newsletter! Thank you to all of our supporters—new and old!
I’m Paul Ciurysek, MD, and this is The USMLE Times: An independent, subscriber-supported newsletter designed to help you survive medical school, pass your USMLE exams, and match into your dream residency program.
Here’s what’s on tap for issue #93 of the USMLE Times:
Question of the Week (Microbiology)
This week’s video training (5 Common Step 1 Prep Mistakes)
Question deep-dive & breakdown
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Let’s dive in!
A 40-year-old female presents to the clinic for 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 minor 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. Phospholipase-induced degradation of the cell membrane
B. Inhibition of neurotransmitter release via protease
C. N-glycosidase inactivation of 60S ribosome
D. Increase of intracellular cAMP via adenylate cyclase
E. Inactivation of elongation factor via ribosyl transferase
The answer & question breakdown is at the bottom of the post.
🔗 LINKS TO RECENT POSTS
USMLE Times Issue #92 - READ HERE
USMLE Practice Question #57 - DO IT HERE
USMLE Practice Question #56 - DO IT HERE
ANSWER + QUESTION BREAKDOWN
The Mental Model for this week’s question:
Step 1. Determine the question’s goal (Identify the mechanism of injury caused by the organism). This is a 2nd order question: 1) ID the organism, 2) Recognize its MOA.
Step 2. Read the vignette and identify the causative organism.
Step 3. Ask yourself how this organism exerts the effects noted in the question.
Step 4. Look at the answer choices to identify the option closest to your statement from “step 3” above.
GENERAL ANALYSIS
The question asks for the mechanism of cellular damage caused by the organism identified in the tissue culture. Given the organism's characteristics and clinical presentation, it is essential to identify the specific toxin and its mechanism of action responsible for the observed necrosis.
ANSWER CHOICES:
ANSWER CHOICE A: Phospholipase-induced degradation of the cell membrane
This is consistent with C. perfrigens, which produces an alpha toxin with phospholipase C activity. This enzyme degrades phospholipids in cell membranes, leading to cell lysis and tissue necrosis. The alpha toxin's phospholipase activity is responsible for the rapid tissue destruction associated with gas gangrene.
ANSWER CHOICE B: Inhibition of neurotransmitter release via protease
This mechanism is associated with botulinum toxin (C. botulinum), which cleaves SNARE proteins necessary for neurotransmitter release at synaptic junctions. It results in flaccid paralysis due to the inability of neurons to release acetylcholine, leading to muscle weakness.
ANSWER CHOICE C: N-glycosidase inactivation of 60S ribosome
This mechanism is characteristic of Shiga toxin and ricin, which remove an adenine residue from the 28S rRNA of the 60S ribosomal subunit, inhibiting protein synthesis. The interruption of protein production leads to cell death.
ANSWER CHOICE D: Increase of intracellular cAMP via adenylate cyclase
This mechanism is seen with toxins like cholera toxin and pertussis toxin, which increase cAMP levels in host cells. Elevated cAMP disrupts ion transport and fluid balance, leading to symptoms such as diarrhea (in cholera) or respiratory secretions (in pertussis).
ANSWER CHOICE E: Inactivation of elongation factor via ribosyl transferase
This mechanism is associated with diphtheria toxin, which inhibits protein synthesis via ADP-ribosylation of elongation factor 2 (EF-2). Impaired protein production results in cell death, contributing to the systemic effects of diphtheria.
THE VERDICT…
The primary virulence factor of Clostridium perfringens responsible for tissue necrosis in gas gangrene is its alpha toxin. This toxin possesses phospholipase C activity, which hydrolyzes phospholipids in cell membranes, leading to cell lysis and extensive tissue destruction.
The rapid progression of necrosis and gas production is characteristic of infections caused by this organism.
Therefore, phospholipase-induced degradation of cell membranes is the correct mechanism describing how this organism causes cellular damage.
FINAL ANSWER: A: Phospholipase-induced degradation of the cell membrane
That’s it for issue #93 of The USMLE Times!
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See you next time 👋