An Enterococcus faecium bloodstream isolate initially susceptible to linezolid develops resistance during prolonged therapy. Sequencing reveals acquisition of the cfr gene. What is the mechanism conferred by cfr?
- A C8 methylation of adenine 2503 in 23S rRNA by a SAM-dependent methyltransferase, reducing linezolid binding ✓
- B Ribosomal protection protein binding the 50S subunit
- C Efflux of oxazolidinones via a major facilitator pump
- D Enzymatic degradation of the oxazolidinone ring by an esterase
Correct answer: A. C8 methylation of adenine 2503 in 23S rRNA by a SAM-dependent methyltransferase, reducing linezolid binding
Explanation
cfr encodes a methyltransferase that methylates C2503 of 23S rRNA at the A8 position, sterically hindering linezolid binding at the peptidyl transferase centre. Because C2503 sits in the overlapping binding site for several drug classes, cfr also confers resistance to phenicols, lincosamides, pleuromutilins and streptogramin C (the PhLOPS-C phenotype). Ribosomal protection proteins mediate tetracycline resistance, and enzymatic drug degradation plays no role in oxazolidinone resistance.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.