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Difficulty: EasyInfectious Disease Mechanisms

An otherwise healthy carpenter is evaluated at an urgent care center for a tender, erythematous, and fluctuant nodule on the left thigh. Vital signs are within normal limits. The clinician performs an incision and drainage, yielding frank pus. A Gram stain of the purulent material demonstrates Gram-positive cocci arranged in grape-like clusters. Subsequent bacterial culture isolates an organism that demonstrates resistance to oxacillin. Which of the following is the most likely molecular mechanism underlying this pathogen's antimicrobial resistance profile?

  1. Synthesis of a modified penicillin-binding proteinAnswer
  2. B
    Enzymatic cleavage of the beta-lactam ring
  3. C
    Structural alteration of the terminal peptide in the cell wall precursor
  4. D
    Decreased intracellular drug accumulation via active efflux pumps
  5. E
    Point mutations in the genes encoding DNA gyrase and topoisomerase IV

Answer

The correct answer is the synthesis of a modified penicillin-binding protein.
The clinical presentation of a purulent soft tissue infection with a Gram stain showing Gram-positive cocci in clusters is highly characteristic of a Staphylococcus aureus infection. Resistance to oxacillin indicates that this is a methicillin-resistant S. aureus (MRSA) strain. MRSA develops resistance to beta-lactamase-resistant penicillins (such as oxacillin, nafcillin, and methicillin) through the acquisition of the staphylococcal cassette chromosome mec (SCCmec), which contains the mecA gene. This gene encodes penicillin-binding protein 2a (PBP2a), a modified transpeptidase that has a significantly reduced affinity for beta-lactam antibiotics. This alteration allows the bacteria to maintain cell wall cross-linking and survive even in the presence of beta-lactam drugs.

Step-by-Step Solution

1
Identify the likely pathogen based on the clinical presentation and Gram stain.
A purulent skin infection yielding Gram-positive cocci in grape-like clusters strongly indicates Staphylococcus aureus.
Recognizing the pathogen is the first step in determining its characteristic resistance mechanisms.
2
Interpret the significance of the antimicrobial susceptibility results.
The organism is resistant to oxacillin, indicating it is a methicillin-resistant Staphylococcus aureus (MRSA) strain.
Oxacillin is a beta-lactamase-resistant penicillin used in laboratory testing to detect methicillin resistance.
3
Identify the molecular mechanism that confers oxacillin/methicillin resistance in this pathogen.
MRSA acquires the mecA gene, which encodes a variant penicillin-binding protein (PBP2a) with very low affinity for beta-lactam antibiotics.
This allows the bacteria to continue synthesizing its cell wall even when beta-lactam antibiotics are present.

Key Concept

Methicillin-resistant Staphylococcus aureus (MRSA) exhibits resistance to all beta-lactam antibiotics (except ceftaroline) through the acquisition of the mecA gene, which encodes a modified transpeptidase known as penicillin-binding protein 2a (PBP2a) that has decreased affinity for these drugs.
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Infectious Disease Mechanisms

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