Linezolid and tedizolid are oxazolidinone antibiotics active against gram-positive organisms including VRE and MRSA. Their mechanism of action is unique because they target:
- A The 50S ribosomal subunit at the peptidyl transferase centre, preventing formation of the 70S initiation complex ✓
- B The 30S ribosomal A site, causing misreading of mRNA codons
- C RNA polymerase sigma factor, preventing transcription initiation
- D The 50S ribosomal L22/L4 proteins, causing premature peptide chain ejection
Explanation
Oxazolidinones bind to the 23S rRNA of the 50S ribosomal subunit at a site that overlaps the A-site of the peptidyl transferase centre (PTC). This prevents the proper positioning of the 50S subunit onto the 30S initiation complex (fMet-tRNA-mRNA), blocking formation of the 70S initiation complex at a very early step in translation. This mechanism is distinct from all other ribosome-targeting antibiotics (chloramphenicol, macrolides, tetracyclines), explaining the lack of cross-resistance. Linezolid also inhibits human mitochondrial ribosome (similar 23S rRNA), explaining myelosuppression with prolonged use.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.