Rifampicin resistance in Mycobacterium tuberculosis is clinically used as a proxy marker for MDR-TB. The molecular basis for rifampicin resistance is:
- A Upregulation of efflux pumps that expel rifampicin from the mycobacterial cell
- B Mutations in the rpoB gene encoding the beta-subunit of RNA polymerase, reducing rifampicin binding affinity at the drug's target ✓
- C Induction of rifampicin-inactivating ADP-ribosyl transferase enzymes
- D Reduced cell wall permeability due to loss of specific porin-like channels
Correct answer: B. Mutations in the rpoB gene encoding the beta-subunit of RNA polymerase, reducing rifampicin binding affinity at the drug's target
Explanation
Rifampicin binds to the beta-subunit of bacterial RNA polymerase (encoded by rpoB), blocking the elongation of nascent RNA at the DNA-RNA polymerase junction. Resistance arises from point mutations in the 81-bp rifampicin resistance-determining region (RRDR) of rpoB, most commonly at codon 531 (S531L) or 526 (H526Y/D). These mutations reduce rifampicin binding without substantially impairing the polymerase function. Xpert MTB/RIF detects rpoB mutations to diagnose rifampicin resistance rapidly as a proxy for MDR-TB.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.