Pyrazinamide is a crucial component of the short-course anti-TB regimen. Its activity is unique because it:

• A Is bactericidal against all tubercle bacilli in neutral and alkaline environments
• B Inhibits mycobacterial cell wall arabinosyl transferase, preventing arabinogalactan synthesis
• C Is uniquely active against intracellular semi-dormant bacilli in an acidic milieu (inside phagolysosomes), requiring conversion to pyrazinoic acid by bacterial pyrazinamidase ✓
• D Inhibits RNA polymerase in mycobacteria, acting synergistically with isoniazid

Explanation

Pyrazinamide (PZA) is a nicotinamide analogue that is converted by mycobacterial pyrazinamidase (pncA gene product) to pyrazinoic acid (POA). POA is protonated at acidic pH and the protonated form disrupts mycobacterial membrane energy transport and inhibits fatty acid synthetase I. Its activity is specific to the acidic environment of phagolysosomes, where persister bacilli reside; this is why PZA uniquely sterilises this otherwise drug-inaccessible compartment and permits 6-month short-course therapy.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.