ArticleScientific reports2017
Anti-tubercular Activity of Pyrazinamide is Independent of trans-Translation and RpsA.
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 30 papers.
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Who cites it
30 citing papers in PubMed, 60 citations in OpenAlex.
- The epidemiology and gene mutation characteristics of pyrazinamide-resistantEmerging microbes & infections · 2025Article
- Pyrazinamide killsbioRxiv : the preprint server for biology · 2025Article
- AACS infectious diseases · 2025Article
- Enhancing diagnostic efficiency of pyrazinamide resistance inCurrent research in microbial sciences · 2025Article
- Bifidobacterium adolescentis is resistant to pyrazinamide, isoniazid, and streptomycin.Scientific reports · 2024Article
- Extraribosomal Functions of Bacterial Ribosomal Proteins-An Update, 2023.International journal of molecular sciences · 2024Review
- Prevalence, Transmission and Genetic Diversity of Pyrazinamide Resistance Among Multidrug-ResistantInfection and drug resistance · 2024Article
- Synthesis, antimycobacterial evaluation, and molecular docking study of 1,2,4-triazole derivatives.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Review
- Selection of Multi-Drug Targets against Drug-ResistantInternational journal of molecular sciences · 2023Article
- Structure activity relationship of pyrazinoic acid analogs as potential antimycobacterial agents.Bioorganic & medicinal chemistry · 2022Article
- Review
- Safe and easy in vitro evaluation of tmRNA-SmpB-mediatedRNA (New York, N.Y.) · 2021Article
- Activity of Pyrazinamide againstAntibiotics (Basel, Switzerland) · 2021Article
- Overcoming the Challenges of Pyrazinamide Susceptibility Testing in Clinical Mycobacterium tuberculosis Isolates.Antimicrobial agents and chemotherapy · 2021Article
- Article
- The Bewildering Antitubercular Action of Pyrazinamide.Microbiology and molecular biology reviews : MMBR · 2020Review
- Metallochaperones Are Needed for Mycobacterium tuberculosis and Escherichia coli Nicotinamidase-Pyrazinamidase Activity.Journal of bacteriology · 2020Article
- Characterization ofFrontiers in microbiology · 2020Article
- Pharmacological and Molecular Mechanisms Behind the Sterilizing Activity of Pyrazinamide.Trends in pharmacological sciences · 2019Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Pyrazinamide (PZA) is a first line anti-tubercular drug for which the mechanism of action remains unresolved. Recently, it was proposed that the active form of PZA, pyrazinoic acid (POA), disrupts the ribosome rescue process of trans-translation in Mycobacterium tuberculosis. This model suggested that POA binds within the carboxy-terminal domain of ribosomal protein S1 (RpsA) and inhibits trans-translation leading to accumulation of stalled ribosomes. Here, we demonstrate that M. tuberculosis RpsA interacts with single stranded RNA, but not with POA. Further, we show that an rpsA polymorphism previously identified in a PZA resistant strain does not confer PZA resistance when reconstructed in a laboratory strain. Finally, by utilizing an in vitro trans-translation assay with purified M. tuberculosis ribosomes we find that an interfering oligonucleotide can inhibit trans-translation, yet POA does not inhibit trans-translation. Based on these findings, we conclude that the action of PZA is entirely independent of RpsA and trans-translation in M. tuberculosis.
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