Isoniazid (INH) resistance in Mycobacterium tuberculosis most commonly arises from mutation in which gene, and what enzyme activity does INH normally inhibit?

• A katG gene mutation; INH (as active intermediate) inhibits InhA (enoyl-ACP reductase) involved in mycolic acid synthesis ✓
• B rpoB gene mutation; INH inhibits RNA polymerase beta-subunit
• C pncA gene mutation; INH inhibits pyrazinamidase
• D gyrA gene mutation; INH inhibits DNA gyrase

Explanation

INH is a prodrug activated by the mycobacterial catalase-peroxidase encoded by katG to form isonicotinoyl-NAD, which inhibits InhA (enoyl-ACP reductase), an enzyme critical for mycolic acid biosynthesis. Resistance most commonly results from katG mutations (loss of prodrug activation) or inhA promoter mutations (overexpression of the target). rpoB mutations confer rifampicin resistance. pncA mutations confer pyrazinamide resistance. gyrA/gyrB mutations confer fluoroquinolone resistance.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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