A healthcare worker exposed to TB converts her tuberculin test from negative to positive. She is placed on isoniazid preventive therapy (IPT). The primary mechanism of isoniazid action is:

• A Inhibition of arabinosyl transferases required for arabinogalactan synthesis
• B Inhibition of InhA (enoyl-ACP reductase) and KasA (beta-ketoacyl-ACP synthase) in mycolic acid synthesis after activation by KatG catalase-peroxidase ✓
• C Inhibition of RNA polymerase beta subunit
• D Generation of reactive nitrogen intermediates that damage DNA

Explanation

Isoniazid is a prodrug activated by the mycobacterial KatG catalase-peroxidase enzyme to form isonicotinoyl radical. The active metabolite forms a covalent adduct with NAD, which inhibits InhA (enoyl-ACP reductase) — the principal target — and KasA (beta-ketoacyl-ACP synthase), disrupting long-chain mycolic acid biosynthesis. Resistance most commonly results from katG mutations (reducing activation) or inhA promoter mutations. Ethambutol inhibits arabinosyl transferases (EmbB); rifampicin inhibits RNA polymerase.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.