The Sound of Evolution
Pyrazinamide
Mechanism of action:
Pyrazinamide is a pyrazinecarboxamide derivative. After entering Mycobacterium tuberculosis, pyrazinamide is hydrolyzed by the bacterial pyrazinamidase/nicotinamidase into pyrazinoic acid. The accumulation of pyrazinoic acid within the bacterium interferes with membrane potential, inhibits energy production and proton motive force, and prevents bacterial survival even under low-metabolic conditions.
Reference(s):
1. Yee D et al. (2003). Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis. Am J Respir Crit Care Med.
2. Boshoff HI et al. (2002). Effects of pyrazinamide on fatty acid synthesis by whole mycobacterial cells and purified fatty acid synthase I. J Bacteriol.
3. Zimhony O et al. (2007). Pyrazinoic acid and its n-propyl ester inhibit fatty acid synthase type I in replicating tubercle bacilli. Antimicrob Agents Chemother.