Enterococcus faecium is isolated from a blood culture. Disc diffusion shows a vancomycin zone of 8 mm (resistant). PCR confirms vanA gene. The mechanism of vanA-mediated resistance is:
- A Mutations in the RNA polymerase gene (rpoB) reducing vancomycin binding to its target
- B Production of vancomycin-inactivating acetyltransferase enzyme encoded on a plasmid
- C Substitution of normal peptidoglycan precursor terminus D-Ala-D-Ala with D-Ala-D-Lac, reducing vancomycin binding affinity by ~1000-fold ✓
- D Efflux pump overexpression removing vancomycin from the periplasmic space before cell wall binding
Explanation
vanA (and vanB) gene clusters in VRE encode ligases that reprogram peptidoglycan synthesis. In the vanA phenotype, the terminal D-Ala-D-Ala of the pentapeptide precursor is replaced by D-Ala-D-Lac (D-lactate). Vancomycin normally binds D-Ala-D-Ala via five hydrogen bonds; replacement with D-Lac removes one critical hydrogen bond (due to an ester replacing an amide linkage), reducing binding affinity ~1000-fold — rendering the antibiotic ineffective. vanA confers high-level resistance to both vancomycin and teicoplanin. vanB confers resistance to vancomycin only (variable expression, teicoplanin-susceptible). VRE treatment options include linezolid and daptomycin.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
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