Linezolid resistance emerging in enterococci and staphylococci through horizontal transfer of the cfr gene is caused by:
- A Ribosomal RNA methyltransferase-mediated methylation of A2503 in the 23S rRNA, blocking drug binding at the peptidyl transferase centre ✓
- B Efflux of the drug via an ABC transporter encoded on the same transposon
- C Mutation of the L4 and L22 ribosomal proteins widening the nascent peptide exit tunnel
- D Enzymatic acetylation of the morpholine ring of linezolid
Correct answer: A. Ribosomal RNA methyltransferase-mediated methylation of A2503 in the 23S rRNA, blocking drug binding at the peptidyl transferase centre
Explanation
The plasmid- and transposon-borne cfr gene encodes a 23S rRNA methyltransferase that adds a methyl group to B2503 within the peptidyl transferase centre, reducing linezolid binding and simultaneously conferring the PhLOPSa phenotype (resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins and streptogramin B). Ribosomal protein L3/L4 alterations and mutations in the 23S rRNA V domain cause resistance too, but they arise by mutation rather than transfer. No enzyme that chemically degrades or acetylates linezolid is known.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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