Pharmacology · Antimicrobials (Cell Wall Inhibitors, Protein Synthesis Inhibitors, Fluoroquinolones)

Linezolid acts on bacterial ribosomes by a unique mechanism that makes cross-resistance with other protein synthesis inhibitors unlikely. This mechanism is:

  • A Inhibiting formation of the 70S initiation complex by binding to the 23S rRNA of the 50S subunit in a unique allosteric site that prevents fMet-tRNA from entering the P site
  • B Inhibiting peptidyl transferase activity on the 50S subunit by binding to the 23S rRNA at domain V
  • C Preventing translocation of the peptidyl-tRNA from A site to P site on the 50S subunit
  • D Blocking aminoacyl-tRNA binding to the A site of the 30S subunit
Correct answer: A. Inhibiting formation of the 70S initiation complex by binding to the 23S rRNA of the 50S subunit in a unique allosteric site that prevents fMet-tRNA from entering the P site

Explanation

Linezolid (an oxazolidinone) uniquely inhibits the initiation of translation by binding to domain V of the 23S rRNA of the 50S subunit, preventing the formation of the functional 70S initiation complex and blocking the entry of fMet-tRNA into the ribosomal P site. This early step in translation is targeted by no other clinically used antibiotic class, explaining the absence of cross-resistance. Chloramphenicol inhibits peptidyl transferase; fusidic acid and macrolides inhibit translocation; tetracyclines block A-site aminoacyl-tRNA entry.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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