Pyrazinamide is inactive against Mycobacterium tuberculosis at neutral pH but becomes bactericidal within acidic phagosomes and caseous foci. Resistance to pyrazinamide most commonly results from:

• A Mutation in rrs conferring altered ribosomal binding
• B Mutation in rpoB altering the RNA polymerase binding site
• C Overexpression of the emb operon causing arabinosyl transferase modification
• D Mutation in the pncA gene encoding pyrazinamidase, preventing conversion to pyrazinoic acid ✓

Explanation

Pyrazinamide is a prodrug that must be converted by mycobacterial pyrazinamidase, encoded by pncA, into active pyrazinoic acid. About 95 percent of pyrazinamide-resistant isolates carry loss-of-function mutations in pncA. The rpoB mutation causes rifampicin resistance, emb overexpression causes ethambutol resistance, and rrs mutations cause aminoglycoside resistance.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.