A hospital outbreak of MRSA is traced to a strain with vanA gene cluster. This organism, unlike typical MRSA, requires treatment with daptomycin. Why does the vanA gene confer resistance to both vancomycin AND cross-resistance to linezolid may develop?
- A vanA encodes efflux pumps that export both vancomycin and linezolid
- B vanA encodes a D-Ala-D-Lac ligase replacing D-Ala-D-Ala in peptidoglycan termini, reducing vancomycin binding; linezolid resistance arises independently via 23S rRNA mutations ✓
- C vanA modifies the 50S ribosomal subunit target reducing linezolid binding
- D vanA mediates beta-lactamase production that destroys vancomycin and linezolid
Correct answer: B. vanA encodes a D-Ala-D-Lac ligase replacing D-Ala-D-Ala in peptidoglycan termini, reducing vancomycin binding; linezolid resistance arises independently via 23S rRNA mutations
Explanation
The vanA gene cluster encodes enzymes that reprogram cell wall synthesis: VanH reduces pyruvate to D-lactate, and VanA forms D-Ala-D-Lac dipeptide (replacing D-Ala-D-Ala). Vancomycin binds D-Ala-D-Ala with 1000-fold higher affinity than D-Ala-D-Lac, so vanA abolishes vancomycin binding. Cross-resistance to linezolid is not encoded by vanA — it occurs independently through mutations in the 23S rRNA gene (domain V) or cfr gene (methyltransferase), hence options B, C, D are incorrect.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.