A 45-year-old man started on antituberculous therapy develops orange discoloration of his urine and tears. The causative drug exerts its antibacterial effect by binding which molecular target?
- A Beta subunit of bacterial DNA-dependent RNA polymerase, blocking transcription initiation ✓
- B Alpha subunit of bacterial RNA polymerase, blocking promoter clearance
- C 30S ribosomal subunit, blocking fMet-tRNA binding
- D Bacterial DNA gyrase, blocking fork progression
Correct answer: A. Beta subunit of bacterial DNA-dependent RNA polymerase, blocking transcription initiation
Explanation
Rifampicin forms a stable complex with the beta subunit (rpoB product) of bacterial DNA-dependent RNA polymerase, sterically blocking extension of the transcript beyond two to three nucleotides, so initiation fails. Mammalian nuclear RNA polymerase is resistant, accounting for selective toxicity. Resistance arises rapidly through point mutations in rpoB. Orange body fluid discoloration is a classic harmless clue to rifampicin therapy.
Reference: Katzung Basic and Clinical Pharmacology, 16th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.