Pyrazinamide (PZA) functions as a prodrug, which is converted into its active form, pyrazinoic acid (POA), by the PZase/nicotinamidase enzyme encoded by the pncA gene of Mycobacterium tuberculosis. Its primary mechanism of action is likely related to pyrazinoic acid. Once pyrazinoic acid penetrates into phagocytes and subsequently into the bacterial cells of Mycobacterium tuberculosis, it is deaminated by amidases within the bacterial cells, converting into pyrazinoic acid that exerts its antibacterial effect. At a pH range of 5-5.5, PZA exhibits its strongest bactericidal activity, making it an optimal therapeutic agent against Mycobacterium tuberculosis residing within phagocytes that grow slowly in an acidic environment.
