ArticleTuberculosis (Edinburgh, Scotland)2013
pncA gene expression and prediction factors on pyrazinamide resistance in Mycobacterium tuberculosis.
Article in Tuberculosis (Edinburgh, Scotland), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Transformer-accelerated discovery of inhibitors targeting the RpsAJournal of cheminformatics · 2026Article
- Comprehensive evaluation of the MeltPro MTB/PZA assay for prediction of pyrazinamide resistance in multidrug-resistant tuberculosis.Microbiology spectrum · 2025Article
- Pyrazinamide-resistant Tuberculosis Obscured From Common Targeted Molecular Diagnostics.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2023Article
- Detection of Mutations inCurrent issues in molecular biology · 2022Article
- Computational modeling and bioinformatic analyses of functional mutations in drug target genes inComputational and structural biotechnology journal · 2021Article
- Direct Determination of Pyrazinamide (PZA) Susceptibility by Sputum Microscopic Observation Drug Susceptibility (MODS) Culture at Neutral pH: the MODS-PZA Assay.Journal of clinical microbiology · 2020Article
- Metallochaperones Are Needed for Mycobacterium tuberculosis and Escherichia coli Nicotinamidase-Pyrazinamidase Activity.Journal of bacteriology · 2020Article
- Pyrazinamide Resistance and Mutation Patterns Among Multidrug-ResistantInfection and drug resistance · 2020Article
- Article
- Prevalence and molecular characterization of pyrazinamide resistance among multidrug-resistant Mycobacterium tuberculosis isolates from Southern China.BMC infectious diseases · 2017Article
- A multiple genome analysis of Mycobacterium tuberculosis reveals specific novel genes and mutations associated with pyrazinamide resistance.BMC genomics · 2017Article
- Cyclic di-GMP regulates Mycobacterium tuberculosis resistance to ethionamide.Scientific reports · 2017Article
- The Rate of Drug-Resistant Tuberculosis in Korean Children and Adolescents Since 2007.Journal of Korean medical science · 2017Article
- Mycobacterium kansasii.Microbiology spectrum · 2017Review
- Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection.The American journal of tropical medicine and hygiene · 2016Article
- Multicenter Study of the Emergence and Genetic Characteristics of Pyrazinamide-Resistant Tuberculosis in China.Antimicrobial agents and chemotherapy · 2016Article
- The efflux pump inhibitor timcodar improves the potency of antimycobacterial agents.Antimicrobial agents and chemotherapy · 2015Article
- Whole genome sequencing based characterization of extensively drug-resistant Mycobacterium tuberculosis isolates from Pakistan.PloS one · 2015Article
- Association between pncA gene mutations, pyrazinamidase activity, and pyrazinamide susceptibility testing in Mycobacterium tuberculosis.Antimicrobial agents and chemotherapy · 2014Article
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8 authors.
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Abstract
Mutations in the pyrazinamidase (PZAse) coding gene, pncA, have been considered as the main cause of pyrazinamide (PZA) resistance in Mycobacterium tuberculosis. However, recent studies suggest there is no single mechanism of resistance to PZA. The pyrazinoic acid (POA) efflux rate is the basis of the PZA susceptibility Wayne test, and its quantitative measurement has been found to be a highly sensitive and specific predictor of PZA resistance. Based on biological considerations, the POA efflux rate is directly determined by the PZAse activity, the level of pncA expression, and the efficiency of the POA efflux pump system. This study analyzes the individual and the adjusted contribution of PZAse activity, pncA expression and POA efflux rate on PZA resistance. Thirty M. tuberculosis strains with known microbiological PZA susceptibility or resistance were analyzed. For each strain, PZAse was recombinantly produced and its enzymatic activity measured. The level of pncA mRNA was estimated by quantitative RT-PCR, and the POA efflux rate was determined. Mutations in the pncA promoter were detected by DNA sequencing. All factors were evaluated by multiple regression analysis to determine their adjusted effects on the level of PZA resistance. Low level of pncA expression associated to mutations in the pncA promoter region was observed in pncA wild type resistant strains. POA efflux rate was the best predictor after adjusting for the other factors, followed by PZAse activity. These results suggest that tests which rely on pncA mutations or PZAse activity are likely to be less predictive of real PZA resistance than tests which measure the rate of POA efflux. This should be further analyzed in light of the development of alternate assays to determine PZA resistance.
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