Pyrazinamide is bactericidal against Mycobacterium tuberculosis only at an acidic pH, such as inside macrophage phagolysosomes and caseous lesions. Its activity depends on conversion to the active compound by which enzyme?

• A Catalase-peroxidase encoded by katG
• B RNA polymerase encoded by rpoB
• C Pyrazinamidase encoded by pncA ✓
• D Dihydrofolate reductase

Explanation

Pyrazinamide is a prodrug that enters bacilli passively and is converted by bacterial pyrazinamidase, the product of the pncA gene, into pyrazinoic acid, its active form. Mutations in pncA confer pyrazinamide resistance, and this is the basis of molecular resistance testing. KatG mutations cause isoniazid resistance, rpoB mutations cause rifampicin resistance, and dihydrofolate reductase is unrelated to any first-line anti-TB drug mechanism.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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