Vancomycin resistance in Enterococcus faecium (VRE) most commonly results from substitution of which cell wall precursor, and which vancomycin resistance gene cluster mediates this?
- A D-Ala-D-Ala replaced by D-Ala-D-Ser; mediated by vanC gene cluster
- B Peptidoglycan cross-links altered by penicillin-binding protein mutation; mediated by vanB
- C D-Ala-D-Ala replaced by D-Ala-D-Asn; mediated by vanE gene cluster
- D D-Ala-D-Ala replaced by D-Ala-D-Lac; mediated by vanA gene cluster ✓
Explanation
The most clinically important vancomycin resistance in Enterococcus involves the vanA gene cluster (on transposon Tn1546), which encodes enzymes that remodel the peptidoglycan precursor terminus from D-Ala-D-Ala to D-Ala-D-Lac (D-Ala-D-lactate). Vancomycin normally binds to D-Ala-D-Ala with high affinity; the substitution of D-Lac for D-Ala reduces binding affinity by ~1000-fold. VanC confers intrinsic low-level resistance in E. gallinarum/E. casseliflavus via D-Ala-D-Ser substitution. VanB also replaces D-Ala-D-Lac but has lower-level, inducible resistance. The penicillin-binding protein mechanism is MRSA-type resistance, not VRE.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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