Pyrazinamide exerts its bactericidal activity against semidormant bacilli inside caseous lesions primarily because of which property?

• A It is converted to pyrazinoic acid, which acts most effectively at acidic pH ✓
• B It inhibits DNA-dependent RNA polymerase at neutral pH
• C It inhibits arabinosyl transferase in the cell wall
• D It generates hydroxyl radicals through Fenton chemistry

Explanation

Pyrazinamide is a prodrug that enters bacilli passively and is converted by the bacterial pyrazinamidase encoded by the pncA gene into pyrazinoic acid. This metabolite disrupts membrane transport and energy metabolism, and its activity is maximal at the acidic pH found within macrophage phagosomes and caseous foci, where other first-line drugs work poorly. It targets semidormant persisters, allowing shortening of therapy to 6 months. Rifampicin inhibits RNA polymerase and fluoroquinolones target DNA gyrase.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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