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

Nat Med. 1996 Jun;2(6):662-7. doi: 10.1038/nm0696-662.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidohydrolases / chemistry
  • Amidohydrolases / genetics*
  • Amidohydrolases / pharmacology*
  • Amino Acid Sequence
  • Base Sequence
  • Cloning, Molecular
  • Drug Resistance, Microbial / genetics*
  • Molecular Sequence Data
  • Mutation*
  • Mycobacterium bovis / drug effects
  • Mycobacterium bovis / enzymology
  • Mycobacterium bovis / genetics
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / enzymology
  • Mycobacterium tuberculosis / genetics*
  • Nicotinamidase / chemistry
  • Nicotinamidase / genetics
  • Transformation, Genetic


  • Amidohydrolases
  • pyrazinamide deamidase
  • Nicotinamidase

Associated data

  • GENBANK/U59967