ArticleNature communications2017
A comprehensive characterization of PncA polymorphisms that confer resistance to pyrazinamide.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 119 citations in OpenAlex.
- Algorithmic Determinants of Performance Heterogeneity in Whole-Genome Sequencing-Based Prediction of Drug Resistance inMicroorganisms · 2026Review
- Predicting pyrazinamide resistance in Mycobacterium tuberculosis using a graph convolutional network.BMC microbiology · 2026Article
- Targeted Next-Generation Sequencing in Drug-Resistant Tuberculosis: WHO Guidance and Practical Implementation Priorities.Biomedicines · 2026Review
- From mutation detection to treatment decisions: CRISPR-enabled diagnostics for drug-resistant tuberculosis.Frontiers in bioengineering and biotechnology · 2026Review
- Combating Drug-Resistant Tuberculosis: Advancements in Diagnostics and Therapeutics.Pulmonary medicine · 2026Review
- Evaluating selection at intermediate scales within genes provides robust identification of genes under positive selection in M. tuberculosis clinical isolates.Tuberculosis (Edinburgh, Scotland) · 2025Article
- The epidemiology and gene mutation characteristics of pyrazinamide-resistantEmerging microbes & infections · 2025Article
- Characterization of Drug Resistance Mutations inMicroorganisms · 2025Article
- Evaluating selection at intermediate scales within genes provides robust identification of genes under positive selection inbioRxiv : the preprint server for biology · 2025Article
- Comprehensive evaluation of the MeltPro MTB/PZA assay for prediction of pyrazinamide resistance in multidrug-resistant tuberculosis.Microbiology spectrum · 2025Article
- Determining the minimum inhibitory concentrations of pyrazinamide againstFrontiers in microbiology · 2025Article
- A simplified pyrazinamidase test forJournal of clinical microbiology · 2024Article
- Integrating bacterial molecular genetics with chemical biology for renewed antibacterial drug discovery.The Biochemical journal · 2024Review
- Biphasic Medium Using Nicotinamide for Detection of Pyrazinamide Resistance inAntibiotics (Basel, Switzerland) · 2024Article
- A robust computational quest: Discovering potential hits to improve the treatment of pyrazinamide-resistant Mycobacterium tuberculosis.Journal of cellular and molecular medicine · 2024Article
- Prediction of pyrazinamide resistance inJAC-antimicrobial resistance · 2024Article
- Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach.Nature communications · 2024Article
- Prevalence, Transmission and Genetic Diversity of Pyrazinamide Resistance Among Multidrug-ResistantInfection and drug resistance · 2024Article
- Clinical Significance of Preoperative Pyrazinamide-Containing Therapy in Tuberculous Constrictive Pericarditis.Infection and drug resistance · 2024Article
- Quantitative measurement of antibiotic resistance inResearch square · 2023Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Tuberculosis chemotherapy is dependent on the use of the antibiotic pyrazinamide, which is being threatened by emerging drug resistance. Resistance is mediated through mutations in the bacterial gene pncA. Methods for testing pyrazinamide susceptibility are difficult and rarely performed, and this means that the full spectrum of pncA alleles that confer clinical resistance to pyrazinamide is unknown. Here, we performed in vitro saturating mutagenesis of pncA to generate a comprehensive library of PncA polymorphisms resultant from a single-nucleotide polymorphism. We then screened it for pyrazinamide resistance both in vitro and in an infected animal model. We identify over 300 resistance-conferring substitutions. Strikingly, these mutations map throughout the PncA structure and result in either loss of enzymatic activity and/or decrease in protein abundance. Our comprehensive mutational and screening approach should stand as a paradigm for determining resistance mutations and their mechanisms of action.The antibiotic pyrazinamide is central to tuberculosis treatment regimens, globally. Despite its efficacy, resistance to the drug is increasing. Here, Eric Rubin and colleagues characterise the genetic basis of pyrazinamide resistance.
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