Linezolid resistance emerges during prolonged therapy in a vancomycin-resistant Enterococcus faecium isolate. Sequencing shows post-translational methylation of adenine 2503 in the 23S rRNA. Which genetic element accounts for this mechanism?
- A vanA ligase altering peptidoglycan termini
- B G2576T point mutation in domain V of the 23S rRNA gene
- C cfr gene encoding a ribosomal RNA methyltransferase ✓
- D erm gene methylating A2058 of the 23S rRNA
Correct answer: C. cfr gene encoding a ribosomal RNA methyltransferase
Explanation
The cfr gene encodes a methyltransferase that adds a methyl group to adenine 2503 of 23S rRNA, the nucleotide targeted by linezolid, oxazolidinones, phenicols, lincosamides and pleuromutilins. Because cfr is carried on mobile elements it can transfer horizontally, unlike the alternative mechanism of G2576T mutation in multiple 23S rRNA copies, which develops stepwise during therapy. vanA alters the peptidoglycan target for glycopeptides only, and erm methylation at C2058 confers MLSb resistance without affecting linezolid.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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