ArticleScientific reports2018
Untargeted metabolomics reveals a new mode of action of pretomanid (PA-824).
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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The trial behind it
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
52 citing papers in PubMed, 104 citations in OpenAlex.
- A novel antituberculosis agent exhibits potent clinical efficacy and good safety profile: an open-label, randomized-controlled, multicenter, phase 2a trial.Signal transduction and targeted therapy · 2025Trial
- Bedaquiline, Pretomanid, Linezolid, and Moxifloxacin: Mechanisms of Action, Drug Interactions, Adverse Effects and Use in Special Situations.Microorganisms · 2026Review
- Combined computational and classical medicinal chemistry procedure to disclose novel pyrrole-based compounds as potential antituberculosis agents.Journal of computer-aided molecular design · 2026Article
- Metabolomic changes in the peripheral blood of wild trapped badgers (Meles meles) correlate with bovine tuberculosis (Mycobacterium bovis) infection status.BMC veterinary research · 2025Article
- Current landscape of innovative drug development and regulatory support in China.Signal transduction and targeted therapy · 2025Review
- Mapping the molecular signature of ABA-regulated gene expression in germinating barley embryos.BMC plant biology · 2025Article
- Compounds Containing 2,3-Bis(phenylamino) Quinoxaline Exhibit Activity Against Methicillin-Resistant Staphylococcus aureus, Enterococcus faecalis, and Their Biofilms.MicrobiologyOpen · 2024Article
- The cap-binding complex modulates ABA-responsive transcript splicing during germination in barley (Hordeum vulgare).Scientific reports · 2024Article
- Antitubercular drugs: possible role of natural products acting as antituberculosis medication in overcoming drug resistance and drug-induced hepatotoxicity.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Advances in Diagnostics and Drug Discovery against Resistant and Latent Tuberculosis Infection.Pharmaceutics · 2023Review
- Wollamide Cyclic Hexapeptides Synergize with Established and New Tuberculosis Antibiotics in Targeting Mycobacterium tuberculosis.Microbiology spectrum · 2023Article
- DprE2 is a molecular target of the anti-tubercular nitroimidazole compounds pretomanid and delamanid.Nature communications · 2023Article
- Sample Preparation in Microbial Metabolomics: Advances and Challenges.Advances in experimental medicine and biology · 2023Article
- Untargeted metabolomics reveals sour jujube kernel benefiting the nutritional value and flavor ofOpen life sciences · 2023Article
- Multi-omics Investigation into the Mechanism of Action of an Anti-tubercular Fatty Acid Analogue.Journal of the American Chemical Society · 2022Article
- Article
- Metabotyping the Welsh population of badgers based on thoracic fluid.Metabolomics : Official journal of the Metabolomic Society · 2022Article
- Defining key metabolic roles in osmotic adjustment and ROS homeostasis in the recretohalophyte Karelinia caspia under salt stress.Physiologia plantarum · 2022Article
- Integrating in vitro metabolomics with a 96-well high-throughput screening platform.Metabolomics : Official journal of the Metabolomic Society · 2022Article
- Uncovering interactions between mycobacterial respiratory complexes to target drug-resistantFrontiers in cellular and infection microbiology · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Pretomanid is a promising anti-tubercular drug currently at clinical phase III, but its mechanisms of action are currently unclear. This study aimed to: (i) reveal the metabolome of Mycobacterium smegmatis under pretomanid treatment; (ii) compare major sources of metabolite variation in bacteria treated with pretomanid treatment and other antibiotics; and (iii) to target metabolites responsible for the killing activity of pretomanid in mycobacteria. Untargeted high-resolution metabolite profiling was carried out using flow infusion electrospray ion high resolution mass spectrometry (FIE-HRMS) to identify and quantify metabolites. The identification of key metabolites was independently confirmed by gas-chromatography time-of flight mass spectrometry (GC-tofMS) in comparison to standards. Pretomanid treatments generated a unique distinctive metabolite profile when compared to ampicillin, ethambutol, ethionamide, isoniazid, kanamycin, linezolid, rifampicin and streptomycin. Metabolites which differed significantly only with pretomanid treatment were identified and mapped on to bacterial metabolic pathways. This targeted the pentose phosphate pathway with significant accumulation seen with fructose-6-phosphate, ribose-5-phosphate and glyceraldehyde-3-phosphate. These effects were linked to the accumulation of a toxic metabolite methylglyoxal. This compound showed significant antimicrobial activity (MIC 0.65 mM) against M. smegmatis.
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Registered trials
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