ArticleThe Journal of antimicrobial chemotherapy2019
Repurposing ethyl bromopyruvate as a broad-spectrum antibacterial.
Article in The Journal of antimicrobial chemotherapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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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
8 citing papers in PubMed, 17 citations in OpenAlex.
- Drug Repurposing: An Emerging Strategy inJournal of microbiology and biotechnology · 2025Review
- Improving the treatment of bacterial infections caused by multidrug-resistant bacteria through drug repositioning.Frontiers in pharmacology · 2024Review
- Non-Antibiotic Drug Repositioning as an Alternative Antimicrobial Approach.Antibiotics (Basel, Switzerland) · 2022Review
- Recent advances to combat ESKAPE pathogens with special reference to essential oils.Frontiers in microbiology · 2022Review
- Diclofenac Resensitizes Methicillin-ResistantAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Potential of Bacterial Cellulose Chemisorbed with Anti-Metabolites, 3-Bromopyruvate or Sertraline, to Fight againstInternational journal of molecular sciences · 2020Article
- Synergistic Therapies as a Promising Option for the Treatment of Antibiotic-ResistantAntibiotics (Basel, Switzerland) · 2020Review
- Bioprospecting for Antibacterial Drugs: a Multidisciplinary Perspective on Natural Product Source Material, Bioassay Selection and Avoidable Pitfalls.Pharmaceutical research · 2020Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe emergence of drug-resistant bacteria is a major hurdle for effective treatment of infections caused by Mycobacterium tuberculosis and ESKAPE pathogens. In comparison with conventional drug discovery, drug repurposing offers an effective yet rapid approach to identifying novel antibiotics.
methodsEthyl bromopyruvate was evaluated for its ability to inhibit M. tuberculosis and ESKAPE pathogens using growth inhibition assays. The selectivity index of ethyl bromopyruvate was determined, followed by time-kill kinetics against M. tuberculosis and Staphylococcus aureus. We first tested its ability to synergize with approved drugs and then tested its ability to decimate bacterial biofilm. Intracellular killing of M. tuberculosis was determined and in vivo potential was determined in a neutropenic murine model of S. aureus infection.
resultsWe identified ethyl bromopyruvate as an equipotent broad-spectrum antibacterial agent targeting drug-susceptible and -resistant M. tuberculosis and ESKAPE pathogens. Ethyl bromopyruvate exhibited concentration-dependent bactericidal activity. In M. tuberculosis, ethyl bromopyruvate inhibited GAPDH with a concomitant reduction in ATP levels and transferrin-mediated iron uptake. Apart from GAPDH, this compound inhibited pyruvate kinase, isocitrate lyase and malate synthase to varying extents. Ethyl bromopyruvate did not negatively interact with any drug and significantly reduced biofilm at a 64-fold lower concentration than vancomycin. When tested in an S. aureus neutropenic thigh infection model, ethyl bromopyruvate exhibited efficacy equal to that of vancomycin in reducing bacterial counts in thigh, and at 1/25th of the dosage.
conclusionsEthyl bromopyruvate exhibits all the characteristics required to be positioned as a potential broad-spectrum antibacterial agent.
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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.