A patient with nosocomial pneumonia due to MRSA is given vancomycin. The mechanism of vancomycin resistance in vancomycin-resistant enterococci (VRE) carrying the vanA gene is:
- A Production of beta-lactamase that hydrolyses the vancomycin molecule
- B Efflux pump overexpression that extrudes vancomycin from the cell
- C Substitution of D-Ala–D-Ala terminus with D-Ala–D-Lac, reducing vancomycin binding affinity 1000-fold ✓
- D Thickening of the peptidoglycan layer to trap and prevent vancomycin from reaching target
Correct answer: C. Substitution of D-Ala–D-Ala terminus with D-Ala–D-Lac, reducing vancomycin binding affinity 1000-fold
Explanation
Vancomycin binds the D-Ala–D-Ala terminus of peptidoglycan precursors, inhibiting transglycosylation and transpeptidation. The vanA gene cluster encodes enzymes that substitute D-Lac for D-Ala at the terminal position; this single change reduces binding affinity by approximately 1000-fold, conferring high-level resistance. Beta-lactamase does not cleave vancomycin (option A); the thickened cell wall trapping mechanism is seen in VISA strains (option D).
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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