A researcher finds a resistant S. aureus strain that carries a plasmid encoding a new vanA-like operon. Based on known mechanisms, what specific biochemical change should they look for to explain high-level vancomycin resistance?

• A. A change in the peptidoglycan precursor terminus from D-Ala-D-Ala to D-Ala-D-Lac (or D-Ala-D-Ser), which reduces vancomycin binding affinity and confers resistance.
• B. An upregulation of human-like membrane lipids in the bacterial membrane that inactivate vancomycin by covalent modification once the drug reaches the cell surface, a widely documented mechanism in gram-positive pathogens.
• C. A mutation that converts peptidoglycan glycan strands to entirely L-amino-acid-based polymers that cannot bind any glycopeptides, which is a well-known and common mechanism in staphylococci.
• D. Complete loss of all peptidoglycan synthesis enzymes rendering the cell wall absent so vancomycin has no substrate and thus appears ineffective, which is the standard evolutionary route to antibiotic resistance.

Answer: (A)