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Difficulty: EasyInfectious Disease Mechanisms

A 32-year-old man comes to the clinic due to a painful, swollen boil on his left thigh. Physical examination shows a 3-cm erythematous, fluctuant skin abscess. He undergoes incision and drainage, and a sample is sent for culture. The culture grows Staphylococcus aureus that is resistant to oxacillin and cefazolin. Which of the following is the primary molecular mechanism responsible for this organism's antibiotic resistance?

  1. A
    Secretion of an enzyme that hydrolyzes the antibiotic's structural ring
  2. B
    Mutation changing the terminal amino acids of cell wall precursors
  3. C
    Downregulation of outer membrane porin channels
  4. Production of an altered penicillin-binding proteinAnswer
  5. E
    Upregulation of transmembrane efflux pumps

Answer

Production of an altered penicillin-binding protein
The correct answer identifies the production of an altered penicillin-binding protein. The patient's culture grew Staphylococcus aureus resistant to oxacillin, confirming an infection with methicillin-resistant Staphylococcus aureus (MRSA). MRSA resistance is primarily mediated by the acquisition of the staphylococcal cassette chromosome mec (SCCmec) containing the mecA gene. This gene encodes for PBP2a, a novel penicillin-binding protein with a significantly reduced binding affinity for all beta-lactam antibiotics, enabling the organism to synthesize peptidoglycan even in the presence of these drugs.

Step-by-Step Solution

1
Analyze the culture results provided in the vignette.
The patient has a skin abscess caused by Staphylococcus aureus that is resistant to oxacillin.
Identifying the specific organism and its resistance profile is necessary to determine the underlying molecular mechanism.
2
Correlate the resistance profile with the clinical entity.
Oxacillin-resistant S. aureus is clinically classified as methicillin-resistant S. aureus (MRSA).
Oxacillin and methicillin are structurally similar, and oxacillin resistance serves as the laboratory marker for MRSA.
3
Recall the molecular mechanism of resistance for MRSA.
MRSA strains acquire the mecA gene, which encodes for a variant penicillin-binding protein (PBP2a).
PBP2a has a very low affinity for beta-lactam antibiotics, allowing the bacteria to continue synthesizing its cell wall even in the presence of the drug.

Key Concept

Methicillin-resistant Staphylococcus aureus (MRSA) resistance is mediated by the mecA gene, which encodes an altered penicillin-binding protein (PBP2a) with reduced affinity for beta-lactam antibiotics.
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Topics

Infectious Disease Mechanisms

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