Pyrazinamide mechanism

The mechanism of action of pyrazinamide is not known; however, it has bacteriostatic action that appears to require metabolic conversion via pyrazinamidases (encoded by the pncA gene) present in M tuberculosis. Resistance occurs via mutations in the gene that encodes enzymes involved in the bioactivation of pyrazinamide and by increased expression of drug efflux systems. This develops rapidly when the drug is used alone, but there is minimal cross-resistance with other antimycobacterial drugs. Some resistant strains lack the pyrazinamidase. Pyrazinamide is active against tubercle bacilli in the acidic environment of lysosomes, and macrophages.