ArticleAntimicrobial agents and chemotherapy2016
Selective Inactivity of Pyrazinamide against Tuberculosis in C3HeB/FeJ Mice Is Best Explained by Neutral pH of Caseum.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed.
- Adjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole-blood bactericidal activity model.Scientific reports · 2018Trial
- Coadministration of Allopurinol To Increase Antimycobacterial Efficacy of Pyrazinamide as Evaluated in a Whole-Blood Bactericidal Activity Model.Antimicrobial agents and chemotherapy · 2017Trial
- MakingCell insight · 2026Review
- Mouse models of tuberculosis uniformly featuring hypoxic necrotic lesions and poor response to chemotherapy.Infection and immunity · 2026Article
- Essential role of MHC II in the antitubercular efficacy of pyrazinamide.Antimicrobial agents and chemotherapy · 2026Article
- Drug Exposure Dictates Evolutionary Dynamics of Drug-Resistant Tuberculosis: A Longitudinal Cohort Study in Beijing, China.Infection and drug resistance · 2026Article
- Mouse Models Uniformly Featuring Human-like Lesions Harboring Drug-tolerantbioRxiv : the preprint server for biology · 2025Article
- Pyrazinamide killsbioRxiv : the preprint server for biology · 2025Article
- Oxidative stress drives potent bactericidal activity of pyrazinamide againstbioRxiv : the preprint server for biology · 2024Article
- Bactericidal and sterilizing activity of novel regimens combining bedaquiline or TBAJ-587 with GSK2556286 and TBA-7371 in a mouse model of tuberculosis.Antimicrobial agents and chemotherapy · 2024Article
- Pyrazinoic acid, the active form of the anti-tuberculosis drug pyrazinamide, and aromatic carboxylic acid analogs are protonophores.Frontiers in molecular biosciences · 2024Article
- A Microtiter Plate Assay at Acidic pH to Identify Potentiators that Enhance Pyrazinamide Activity Against Mycobacterium tuberculosis.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Inhibition of host PARP1 contributes to the anti-inflammatory and antitubercular activity of pyrazinamide.Nature communications · 2023Article
- Drug distribution and efficacy of the DprE1 inhibitor BTZ-043 in the C3HeB/FeJ mouse tuberculosis model.Antimicrobial agents and chemotherapy · 2023Article
- Mycobacterial Genetic Technologies for Probing the Host-Pathogen Microenvironment.Infection and immunity · 2023Review
- Article
- Efficacy of Replacing Linezolid with OTB-658 in Anti-Tuberculosis Regimens in Murine Models.Antimicrobial agents and chemotherapy · 2023Article
- Advances in the design of combination therapies for the treatment of tuberculosis.Expert opinion on drug discovery · 2023Review
- Types and functions of heterogeneity in mycobacteria.Nature reviews. Microbiology · 2022Review
- Novel Regimens of Bedaquiline-Pyrazinamide Combined with Moxifloxacin, Rifabutin, Delamanid and/or OPC-167832 in Murine Tuberculosis Models.Antimicrobial agents and chemotherapy · 2022Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Pyrazinamide (PZA) is one of only two sterilizing drugs in the first-line antituberculosis regimen. Its activity is strongly pH dependent; the MIC changes by several orders of magnitude over a range of pH values that may be encountered in various in vivo compartments. We recently reported selective inactivity of PZA in a subset of C3HeB/FeJ mice with large caseous lung lesions. In the present study, we evaluated whether such inactivity was explained by poor penetration of PZA into such lesions or selection of drug-resistant mutants. Despite demonstrating similar dose-proportional PZA exposures in plasma, epithelial lining fluid, and lung lesions, no dose response was observed in a subset of C3HeB/FeJ mice with the highest CFU burden. Although PZA-resistant mutants eventually replaced the susceptible bacilli in BALB/c mice and in C3HeB/FeJ mice with low total CFU burdens, they never exceeded 1% of the total population in nonresponding C3HeB/FeJ mice. The selective inactivity of PZA in large caseous lesions of C3HeB/FeJ mice is best explained by the neutral pH of liquefying caseum.
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