Vancomycin-resistant Enterococcus (VRE) carrying the vanA gene cluster exhibits resistance by which precise molecular mechanism?
- A Enzymatic hydrolysis of the vancomycin lactone ring by a VanX enzyme
- B Methylation of the 23S rRNA vancomycin-binding domain by a VanA methyltransferase
- C Alteration of peptidoglycan precursor terminus from D-Ala-D-Ala to D-Ala-D-Lac, reducing vancomycin binding affinity 1000-fold ✓
- D Overexpression of efflux pumps (VanABC transporter) that actively export vancomycin from the periplasm
Correct answer: C. Alteration of peptidoglycan precursor terminus from D-Ala-D-Ala to D-Ala-D-Lac, reducing vancomycin binding affinity 1000-fold
Explanation
The VanA cluster encodes VanH (a dehydrogenase producing D-Lac from pyruvate), VanA (a ligase replacing D-Ala with D-Lac in the dipeptide), and VanX (a dipeptidase eliminating residual D-Ala-D-Ala). The resulting D-Ala-D-Lac terminus has a 1000-fold lower affinity for vancomycin because the loss of the NH hydrogen-bond donor (replaced by ester oxygen of lactate) removes one of five critical hydrogen bonds. VanA phenotype is inducible and transferable; options A, C, D describe incorrect mechanisms.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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