Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the antituberculous drug pyrazinamide in tubercle bacillus

Angelo Scorpio, Ying Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Naturally pyrazinamide (PZA)-resistant Mycobacterium bovis and acquired PZA-resistant M. tuberculosis strains lose pyrazinamidase (PZase). To investigate the molecular mechanism of PZA resistance, we have cloned the gene (pncA) encoding M. tuberculosis PZase. Mutations in pncA were identified in both types of PZA-resistant strains, and transformation of these strains with a functional pncA gene restored PZase activity and PZA susceptibility. These findings, besides providing the basis for understanding how PZA works, should have implications for rapid detection of PZA-resistant clinical isolates of M. tuberculosis and also for rapid differentiation of M. bovis from M. tuberculosis strains.

Original languageEnglish (US)
Pages (from-to)662-667
Number of pages6
JournalNature medicine
Volume2
Issue number6
DOIs
StatePublished - Jul 4 1996

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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