Vancomycin inhibits cell wall synthesis by binding to D-Ala-D-Ala terminus of peptidoglycan precursors. Vancomycin-resistant Enterococcus (VRE) employs the vanA operon to replace D-Ala-D-Ala with:

• A D-Ala-D-Ser, reducing vancomycin affinity ~7-fold
• B L-Ala-D-Ala, preventing glycopeptide binding entirely
• C D-Glu-D-Ala, sterically hindering glycopeptide access
• D D-Ala-D-Lac, reducing vancomycin affinity ~1000-fold ✓

Explanation

The vanA operon encodes ligases that incorporate D-lactate instead of D-alanine at the terminal position, producing D-Ala-D-Lac. The loss of a single hydrogen bond between vancomycin and D-Lac reduces binding affinity approximately 1000-fold, conferring high-level resistance (MIC >256 mg/L). The vanB operon also produces D-Ala-D-Lac but is inducible and typically gives lower-level resistance.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.