ArticleScientific reports2017
A Multinational Analysis of Mutations and Heterogeneity in PZase, RpsA, and PanD Associated with Pyrazinamide Resistance in M/XDR Mycobacterium tuberculosis.
Article in Scientific reports, 2017. 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, 38 citations in OpenAlex.
- Pervasive genome structure heterogeneity iniScience · 2026Article
- The Identification of Novel Mutations in ATP-Dependent Protease ClpC1 Assists in the Molecular Diagnosis of Obscured Pyrazinamide-Resistant Tuberculosis Clinical Isolates.Microorganisms · 2025Article
- Enhancing diagnostic efficiency of pyrazinamide resistance inCurrent research in microbial sciences · 2025Article
- Oxidative stress drives potent bactericidal activity of pyrazinamide againstbioRxiv : the preprint server for biology · 2024Article
- Prediction of pyrazinamide resistance inJAC-antimicrobial resistance · 2024Article
- Prevalence, Transmission and Genetic Diversity of Pyrazinamide Resistance Among Multidrug-ResistantInfection and drug resistance · 2024Article
- Lineage classification and antitubercular drug resistance surveillance ofMicrobiology spectrum · 2023Article
- Overcoming the Challenges of Pyrazinamide Susceptibility Testing in Clinical Mycobacterium tuberculosis Isolates.Antimicrobial agents and chemotherapy · 2021Article
- Laboratory Evaluation of a Lateral-Flow Cell for Molecular Detection of First-Line and Second-Line Antituberculosis Drug Resistance.Journal of clinical microbiology · 2020Article
- Migrations do not modify Mycobacterium tuberculosis resistance rates: a 20-year retrospective study.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2020Article
- The Bewildering Antitubercular Action of Pyrazinamide.Microbiology and molecular biology reviews : MMBR · 2020Review
- Characterization ofFrontiers in microbiology · 2020Article
- Detection of Novel Gene Mutations Associated with Pyrazinamide Resistance in Multidrug-ResistantInfection and drug resistance · 2020Article
- Molecular characterization of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates identifies local transmission of infection in Kuwait, a country with a low incidence of TB and MDR-TB.European journal of medical research · 2019Article
- Pyrazinoic Acid Inhibits the Bifunctional Enzyme (Rv2783) inPathogens (Basel, Switzerland) · 2019Article
- Introducing RpsA Point Mutations Δ438A and D123A into the Chromosome of Mycobacterium tuberculosis Confirms Their Role in Causing Resistance to Pyrazinamide.Antimicrobial agents and chemotherapy · 2019Article
- MODS-Wayne, a Colorimetric Adaptation of the Microscopic-Observation Drug Susceptibility (MODS) Assay for Detection ofJournal of clinical microbiology · 2019Article
- Occurrence of disputed rpoB mutations among Mycobacterium tuberculosis isolates phenotypically susceptible to rifampicin in a country with a low incidence of multidrug-resistant tuberculosis.BMC infectious diseases · 2019Article
- Improved Bactec MGIT 960 Pyrazinamide Test Decreases Detection of False Mycobacterium tuberculosis Pyrazinamide Resistance.Journal of clinical microbiology · 2017Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Pyrazinamide (PZA) is an important first-line drug in all existing and new tuberculosis (TB) treatment regimens. PZA-resistance in M. tuberculosis is increasing, especially among M/XDR cases. Noted issues with PZA Drug Susceptibility Testing (DST) have driven the search for alternative tests. This study provides a comprehensive assessment of PZA molecular diagnostics in M/XDR TB cases. A set of 296, mostly XDR, clinical M. tuberculosis isolates from four countries were subjected to DST for eight drugs, confirmatory Wayne's assay, and whole-genome sequencing. Three genes implicated in PZA resistance, pncA, rpsA, and panD were investigated. Assuming all non-synonymous mutations cause resistance, we report 90% sensitivity and 65% specificity for a pncA-based molecular test. The addition of rpsA and panD potentially provides 2% increase in sensitivity. Molecular heterogeneity in pncA was associated with resistance and should be evaluated as a diagnostic tool. Mutations near the N-terminus and C-terminus of PZase were associated with East-Asian and Euro-American lineages, respectively. Finally, Euro-American isolates are most likely to have a wild-type PZase and escape molecular detection. Overall, the 8-10% resistance without markers may point to alternative mechanisms of resistance. Confirmatory mutagenesis may improve the disconcertingly low specificity but reduce sensitivity since not all mutations may cause resistance.
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