Vancomycin inhibits bacterial cell wall synthesis by a mechanism distinct from beta-lactams. Which specific step does vancomycin target?
- A Inhibits transpeptidase (PBP) enzyme that cross-links peptidoglycan
- B Inhibits the MurA enzyme in the cytoplasm, blocking UDP-NAM synthesis
- C Binds to the D-Ala-D-Ala terminus of peptidoglycan precursors, sterically blocking transglycosylation and transpeptidation ✓
- D Disrupts the bacterial cell membrane by forming pores
Correct answer: C. Binds to the D-Ala-D-Ala terminus of peptidoglycan precursors, sterically blocking transglycosylation and transpeptidation
Explanation
Vancomycin is a glycopeptide that binds non-covalently but with very high affinity to the D-Ala-D-Ala dipeptide terminus of the lipid II peptidoglycan precursor. This bulky binding sterically hinders the transglycosylase and transpeptidase enzymes required to polymerize and cross-link the growing peptidoglycan chain. Vancomycin-resistant Enterococcus (VRE) evades this by modifying the terminus to D-Ala-D-Lac, reducing vancomycin binding 1000-fold. This mechanism differs from beta-lactams, which form covalent bonds with PBPs.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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