Rifampicin monoresistance in M. tuberculosis most commonly results from mutation in which specific region of the rpoB gene?

• A katG codon 315 (catalase-peroxidase)
• B inhA promoter region at −15 position
• C pncA gene encoding pyrazinamidase
• D Codons 507–533 of rpoB (rifampicin resistance-determining region, RRDR) ✓

Explanation

Rifampicin resistance in M. tuberculosis is caused by mutations in the rpoB gene (encoding the beta subunit of RNA polymerase), particularly in the 81-bp rifampicin resistance-determining region (RRDR) spanning codons 507–533 (historical numbering 516–533). The most common mutation is at codon 531 (Ser531Leu) and codon 516 (Asp516Val/Tyr), collectively accounting for >95% of rifampicin resistance. Detection by Xpert MTB/RIF assay (GeneXpert) targets the rpoB RRDR — probe non-hybridisation indicates RRDR mutation. katG Ser315 and inhA promoter −15 mutations are associated with isoniazid resistance; pncA mutations confer pyrazinamide resistance.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

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