Which antibiotic resistance mechanism is conferred by the mecA gene in methicillin-resistant Staphylococcus aureus (MRSA)?

Question

Accepted Answer

D. Altered penicillin-binding protein (PBP2a) with low affinity for β-lactams. ## mecA Gene and MRSA Resistance Mechanism

**Key Point:** The mecA gene encodes an altered penicillin-binding protein (PBP2a) that has dramatically reduced affinity for β-lactam antibiotics, allowing continued cell wall synthesis even in the presence of β-lactams.

### Molecular Basis of mecA-Mediated Resistance

1. **Normal PBPs (PBP1, PBP2, PBP3):** Bind β-lactams with high affinity → inhibition of transpeptidation → cell wall disruption
2. **PBP2a (encoded by mecA):** 
   - Has altered active site geometry
   - Binds β-lactams with very low affinity (Km ~1000× higher)
   - Maintains transpeptidase activity despite β-lactam presence
   - Allows continued peptidoglycan cross-linking
   - Result: **Resistance to all β-lactams including methicillin, oxacillin, nafcillin**

### Comparison of S. aureus Resistance Mechanisms

| Mechanism | Gene(s) | Antibiotic Class | Resistance Pattern |
|---|---|---|---|
| **PBP2a alteration** | **mecA** | **β-lactams** | **Broad (MRSA phenotype)** |
| β-lactamase production | blaZ | β-lactams (not β-lactamase inhibitors) | Penicillin, ampicillin only |
| Ribosomal methylation | ermC, ermA | Macrolides, lincosamides | MLSB resistance |
| Efflux pumps | norA, norB | Fluoroquinolones | Reduced fluoroquinolone susceptibility |
| Vancomycin resistance | vanA, vanB | Glycopeptides | Rare in S. aureus |

**High-Yield:** MRSA is defined by mecA presence (genotypic) or oxacillin/cefoxitin resistance (phenotypic). PBP2a is the sole mechanism — not β-lactamase.

**Mnemonic:** **mecA = Modified Enzyme Creates Antibiotic resistance** — the altered PBP2a is the "modified enzyme."

**Clinical Pearl:** Vancomycin or linezolid are used for MRSA infections because they bypass the PBP2a mechanism entirely — vancomycin inhibits earlier steps in peptidoglycan synthesis (D-Ala-D-Ala), and linezolid inhibits protein synthesis.

Answer

A. Modification of the peptidoglycan cross-linking site

Answer

B. Efflux pump-mediated extrusion of β-lactam antibiotics

Answer

C. Production of β-lactamase that hydrolyzes the β-lactam ring

Which antibiotic resistance mechanism is conferred by the mecA gene in methicillin-resistant Staphylococcus aureus (MRSA)?

Explanation

mecA Gene and MRSA Resistance Mechanism

Molecular Basis of mecA-Mediated Resistance

Comparison of S. aureus Resistance Mechanisms

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Mechanism	Gene(s)	Antibiotic Class	Resistance Pattern
PBP2a alteration	mecA	β-lactams	Broad (MRSA phenotype)
β-lactamase production	blaZ	β-lactams (not β-lactamase inhibitors)	Penicillin, ampicillin only
Ribosomal methylation	ermC, ermA	Macrolides, lincosamides	MLSB resistance
Efflux pumps	norA, norB	Fluoroquinolones	Reduced fluoroquinolone susceptibility
Vancomycin resistance	vanA, vanB	Glycopeptides	Rare in S. aureus