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

The Journal of Infectious Diseases
M SalfingerL B Reller

Abstract

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.

Citations

Aug 1, 1994·International Journal of Antimicrobial Agents·V St Georgiev
Feb 1, 1993·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·K Fuursted
Nov 15, 2006·Antimicrobial Agents and Chemotherapy·Oren ZimhonyWilliam R Jacobs
Feb 2, 2011·Antimicrobial Agents and Chemotherapy·Zahoor AhmadPetros C Karakousis
Sep 1, 1995·Antimicrobial Agents and Chemotherapy·S YamamotoT Ura
Jul 18, 2002·Antimicrobial Agents and Chemotherapy·Takemasa TakiiKikuo Onozaki
Jan 28, 2005·Antimicrobial Agents and Chemotherapy·Takemasa TakiiKikuo Onozaki
Dec 1, 1992·The American Review of Respiratory Disease·J A SbarbaroA J Crowle
Mar 15, 2005·Clinical Pharmacokinetics·Vincent Launay-VacherGilbert Deray
Nov 2, 2015·Advances in Medical Sciences·Moses NjireTianyu Zhang
Dec 1, 1996·Tubercle and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease·J A SbarbaroA J Crowle
Jun 1, 1992·The Journal of Pediatrics·J R StarkeJ Jereb
Jan 5, 2013·The Brazilian Journal of Infectious Diseases : an Official Publication of the Brazilian Society of Infectious Diseases·Adeeb ShehzadYoung Sup Lee
Jul 13, 2002·Biopharmaceutics & Drug Disposition·Aida MehmedagicOlivier Lafont
Oct 31, 2019·The Journal of Infectious Diseases·Jason D SimmonsThomas R Hawn
Nov 2, 2019·EBioMedicine·Elise A Lamont, Anthony D Baughn
May 29, 1999·Antimicrobial Agents and Chemotherapy·J E ConteE Zurlinden
Jun 23, 2021·Nature Communications·Pierre SantucciMaximiliano G Gutierrez
Feb 24, 2001·Current Problems in Pediatrics·K C Smith

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