A hospital reports several Enterococcus faecium bloodstream isolates that became linezolid resistant during prolonged therapy. Sequencing shows no cfr gene, but multiple copies of the 23S rRNA gene carry a G2576T transition. The resistance mechanism demonstrated here is:
- A Enzymatic degradation of the drug by a hydrolase
- B Efflux mediated by an ABC transporter
- C Target modification by ribosomal RNA mutation decreasing linezolid binding ✓
- D Altered permeability of the outer membrane
Correct answer: C. Target modification by ribosomal RNA mutation decreasing linezolid binding
Explanation
Linezolid binds the 50S peptidyl-transferase centre near the P site. Mutations such as G2576T in domain V of 23S rRNA reduce binding affinity; because bacteria carry multiple rrn copies, the number of mutated copies determines the level of resistance. The cfr ribosomal methyltransferase gene confers resistance by methylating A2503, and it is the classic alternative mechanism when sequencing excludes 23S mutation.
Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.