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Pyrazinamide and pyrazinoic acid activity against tubercle bacilli in cultured human macrophages and in the BACTEC system.

Publication ,  Journal Article
Salfinger, M; Crowle, AJ; Reller, LB
Published in: J Infect Dis
July 1990

Pyrazinamide (PZA) has become an essential component of current 6-month regimens for therapy of tuberculosis. Susceptible strains of tubercle bacilli convert PZA to pyrazinoic acid (POA) through pyrazinamidase (PZase), which resistant strains and Mycobacterium bovis bacille Calmette-Guérin lack. PZA susceptibility results obtained in cultured human macrophages were compared with those in the broth BACTEC system with 7H12 medium at pH 6.0 for strains known to be PZase-positive or -negative. Although added POA was unable to inhibit tubercle bacilli in cultured macrophages, it was able to inhibit them at very high concentrations in the BACTEC broth. Intracellularly formed POA would not be able to escape from the macrophage, and therefore would accumulate sufficiently to lower pH to toxic levels for tubercle bacilli. The results suggest that the cultured macrophages contribute actively or passively to the effectiveness of PZA, such as through the proposed mechanism of low pH generated by PZase in the phagolysosomes.

Duke Scholars

Published In

J Infect Dis

DOI

ISSN

0022-1899

Publication Date

July 1990

Volume

162

Issue

1

Start / End Page

201 / 207

Location

United States

Related Subject Headings

  • Pyrazinamide
  • Mycobacterium tuberculosis
  • Mycobacterium bovis
  • Microbiology
  • Macrophages
  • Hydrogen-Ion Concentration
  • Humans
  • Culture Media
  • Cells, Cultured
  • Amidohydrolases
 

Citation

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MLA
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Salfinger, M., Crowle, A. J., & Reller, L. B. (1990). Pyrazinamide and pyrazinoic acid activity against tubercle bacilli in cultured human macrophages and in the BACTEC system. J Infect Dis, 162(1), 201–207. https://doi.org/10.1093/infdis/162.1.201
Salfinger, M., A. J. Crowle, and L. B. Reller. “Pyrazinamide and pyrazinoic acid activity against tubercle bacilli in cultured human macrophages and in the BACTEC system.J Infect Dis 162, no. 1 (July 1990): 201–7. https://doi.org/10.1093/infdis/162.1.201.
Salfinger, M., et al. “Pyrazinamide and pyrazinoic acid activity against tubercle bacilli in cultured human macrophages and in the BACTEC system.J Infect Dis, vol. 162, no. 1, July 1990, pp. 201–07. Pubmed, doi:10.1093/infdis/162.1.201.
Journal cover image

Published In

J Infect Dis

DOI

ISSN

0022-1899

Publication Date

July 1990

Volume

162

Issue

1

Start / End Page

201 / 207

Location

United States

Related Subject Headings

  • Pyrazinamide
  • Mycobacterium tuberculosis
  • Mycobacterium bovis
  • Microbiology
  • Macrophages
  • Hydrogen-Ion Concentration
  • Humans
  • Culture Media
  • Cells, Cultured
  • Amidohydrolases