MUTATIONS IN PNCA, A GENE ENCODING PYRAZINAMIDASE NICOTINAMIDASE, CAUSE RESISTANCE TO THE ANTITUBERCULOUS DRUG PYRAZINAMIDE IN TUBERCLE BACILLUS/

Naturally pyrazinamide (PZA)-resistant Mycobacterium bovis and acquire d PZA-resistant M, tuberculosis strains lose pyrazinamidase (PZase). T o investigate the molecular mechanism of PZA resistance, we have clone d the gene (pncA) encoding M, tuberculosis PZase. Mutations in pncA we re identified in both types of PZA-resistant strains, and transformati on of these strains with a functional pncA gene restored PZase activit y and PZA susceptibility. These findings, besides providing the basis for understanding how PZA works, should have implications for rapid de tection of PZA-resistant clinical isolates of M. tuberculosis and also for rapid differentiation of M. bovis from M. tuberculosis strains.