Pyrazinamide is bactericidal against semi-dormant bacilli inside caseous lesions. Its activity is strictly dependent on which property of its site of action?

• A Neutral pH, requiring bacterial catalase-peroxidase activation
• B Acidic pH, where the drug is converted to pyrazinoic acid by bacterial pyrazinamidase ✓
• C Alkaline pH, enhancing diffusion through the mycolic acid layer
• D Oxygen tension, because the prodrug requires aerobic respiration

Explanation

Pyrazinamide enters bacilli by passive diffusion and is converted by the bacterial enzyme pyrazinamidase (encoded by pncA) into pyrazinoic acid, which disrupts mycobacterial membranes. This conversion and activity occur only at acidic pH, so the drug acts on bacilli within acidified phagosomes and caseous foci. Loss-of-function mutations in pncA confer resistance. It has no role against actively replicating extracellular bacilli in neutral-pH cavities.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.