Vancomycin inhibits cell wall synthesis by binding D-Ala-D-Ala terminus of peptidoglycan precursors. Vancomycin-resistant Enterococcus (VRE) with vanA gene exhibits resistance via which precise mechanism?

• A Enzymatic degradation of vancomycin by a vancomycin esterase
• B Efflux pump overexpression that removes vancomycin before it can bind
• C Thickening of the outer membrane preventing vancomycin penetration to the cell wall
• D Reprogramming of peptidoglycan terminus from D-Ala-D-Ala to D-Ala-D-Lac, reducing vancomycin binding affinity 1000-fold ✓

Explanation

The vanA operon encodes ligases that substitute D-lactate for the terminal D-alanine in the peptidoglycan precursor, forming D-Ala-D-Lac instead of D-Ala-D-Ala. This single substitution abolishes the hydrogen bond at the binding site, reducing vancomycin affinity by approximately 1000-fold. The vanA gene is plasmid-borne, enabling horizontal transfer to other organisms including Staphylococcus aureus (VRSA). Oritavancin and dalbavancin are newer lipoglycopeptides that retain activity against some VRE phenotypes through a second binding mechanism.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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