Vancomycin-resistant Enterococcus (VRE) with the VanA phenotype is resistant due to which precise molecular mechanism?
- A Substitution of D-Ala-D-Ala terminal residue with D-Ala-D-Lac, reducing vancomycin binding affinity 1000-fold ✓
- B Production of beta-lactamase that hydrolyses the vancomycin molecule
- C Efflux pump that transports vancomycin out of the bacterial cell
- D Modification of PBP2a with reduced affinity for vancomycin
Correct answer: A. Substitution of D-Ala-D-Ala terminal residue with D-Ala-D-Lac, reducing vancomycin binding affinity 1000-fold
Explanation
Vancomycin exerts its effect by binding the D-Ala-D-Ala terminal of peptidoglycan precursors, inhibiting transglycosylation. VanA-type resistance is conferred by the van gene cluster, which reprograms the peptidoglycan synthesis to produce D-Ala-D-Lac termini instead. The ester bond in D-Lac compared to the amide bond in D-Ala eliminates one hydrogen bond, reducing binding affinity by approximately 1000-fold. Beta-lactamase and PBP2a modifications are mechanisms of beta-lactam resistance, not vancomycin resistance.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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