ArticleScience (New York, N.Y.)2011
Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis.
Article in Science (New York, N.Y.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 231 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
231 citing papers in PubMed, 2 syntheses or guidelines pooled it, 508 citations in OpenAlex.
- Systematic review of mutations in pyrazinamidase associated with pyrazinamide resistance in Mycobacterium tuberculosis clinical isolates.Antimicrobial agents and chemotherapy · 2015Pooled it
- A Global Perspective on Pyrazinamide Resistance: Systematic Review and Meta-Analysis.PloS one · 2015Pooled it
- Effects of mutations conferring pyrazinamide resistance among multidrug-resistant tuberculosis isolates from China.Microbiology spectrum · 2026Article
- Transformer-accelerated discovery of inhibitors targeting the RpsAJournal of cheminformatics · 2026Article
- Influence of SmpB and ClpX interactions and interactomes on the transcription profile of Mycobacterium tuberculosis.The Biochemical journal · 2026Article
- Drug Exposure Dictates Evolutionary Dynamics of Drug-Resistant Tuberculosis: A Longitudinal Cohort Study in Beijing, China.Infection and drug resistance · 2026Article
- The epidemiology and gene mutation characteristics of pyrazinamide-resistantEmerging microbes & infections · 2025Article
- Pyrazinamide killsbioRxiv : the preprint server for biology · 2025Article
- Characterization of Drug Resistance Mutations inMicroorganisms · 2025Article
- Comprehensive evaluation of the MeltPro MTB/PZA assay for prediction of pyrazinamide resistance in multidrug-resistant tuberculosis.Microbiology spectrum · 2025Article
- The role of bacterial metabolism in antimicrobial resistance.Nature reviews. Microbiology · 2025Review
- Bacterial ribosome heterogeneity facilitates rapid response to stress.Journal of bacteriology · 2025Review
- The Identification of Novel Mutations in ATP-Dependent Protease ClpC1 Assists in the Molecular Diagnosis of Obscured Pyrazinamide-Resistant Tuberculosis Clinical Isolates.Microorganisms · 2025Article
- Development of a multiplex loop-mediated isothermal amplification (LAMP) method for differential detection ofMicrobiology spectrum · 2025Article
- Development and validation of a liquid chromatography-tandem mass spectrometry assay for the simultaneous analysis of isoniazid and pyrazinamide in cerebrospinal fluid.Journal of pharmaceutical and biomedical analysis · 2025Article
- Differential scanning fluorimetry followed by microscale thermophoresis and/or isothermal titration calorimetry as an efficient tool for ligand screening.Biophysical reviews · 2025Review
- Determining the minimum inhibitory concentrations of pyrazinamide againstFrontiers in microbiology · 2025Article
- Residual host cell proteins: sources, properties, detection methods and data acquisition modes.Frontiers in microbiology · 2025Review
- A scoping review about smoking, smoking cessation and their effects on anti-tuberculosis agents: insights into drug metabolisms, safety, and effectiveness.Frontiers in pharmacology · 2025Review
- Sophorolipid: An Effective Biomolecule for Targeting Microbial Biofilms.Current microbiology · 2024Review
171 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Pyrazinamide (PZA) is a first-line tuberculosis drug that plays a unique role in shortening the duration of tuberculosis chemotherapy. PZA is hydrolyzed intracellularly to pyrazinoic acid (POA) by pyrazinamidase (PZase, encoded by pncA), an enzyme frequently lost in PZA-resistant strains, but the target of POA in Mycobacterium tuberculosis has remained elusive. Here, we identify a previously unknown target of POA as the ribosomal protein S1 (RpsA), a vital protein involved in protein translation and the ribosome-sparing process of trans-translation. Three PZA-resistant clinical isolates without pncA mutation harbored RpsA mutations. RpsA overexpression conferred increased PZA resistance, and we confirmed that POA bound to RpsA (but not a clinically identified ΔAla mutant) and subsequently inhibited trans-translation rather than canonical translation. Trans-translation is essential for freeing scarce ribosomes in nonreplicating organisms, and its inhibition may explain the ability of PZA to eradicate persisting organisms.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.