ArticleAntimicrobial agents and chemotherapy2016
Untargeted Metabolomics To Ascertain Antibiotic Modes of Action.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 96 citations in OpenAlex.
- Article
- Antibiotic resistance inFrontiers in microbiology · 2026Review
- Usnic acid impacts energy production and iron metabolism inmSystems · 2025Article
- Advancing antibiotic discovery with bacterial cytological profiling: a high-throughput solution to antimicrobial resistance.Frontiers in microbiology · 2025Review
- Beyond antibiotics: exploring multifaceted approaches to combat bacterial resistance in the modern era: a comprehensive review.Frontiers in cellular and infection microbiology · 2025Review
- Investigation of antibacterial mode of action of ω-aminoalkoxylxanthones by NMR-based metabolomics and molecular docking.Metabolomics : Official journal of the Metabolomic Society · 2024Article
- Transcriptomic investigations of polymyxins and colistin/sulbactam combination against carbapenem-resistantComputational and structural biotechnology journal · 2024Article
- Advancing Anticancer Drug Discovery: Leveraging Metabolomics and Machine Learning for Mode of Action Prediction by Pattern Recognition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Metabolomics analysis of the lactobacillus plantarum ATCC 14917 response to antibiotic stress.BMC microbiology · 2024Article
- Article
- Integrated Transcriptomic and Metabolomic Mapping Reveals the Mechanism of Action of Ceftazidime/Avibactam against Pan-Drug-ResistantACS infectious diseases · 2023Article
- The Combination of Antibiotic and Non-Antibiotic Compounds Improves Antibiotic Efficacy against Multidrug-Resistant Bacteria.International journal of molecular sciences · 2023Review
- Empowering drug off-target discovery with metabolic and structural analysis.Nature communications · 2023Article
- Untangling the Complexities of Processing and Analysis for Untargeted LC-MS Data Using Open-Source Tools.Metabolites · 2023Article
- Overview on Strategies and Assays for Antibiotic Discovery.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Exogenous metabolite feeding on altering antibiotic susceptibility in Gram-negative bacteria through metabolic modulation: a review.Metabolomics : Official journal of the Metabolomic Society · 2022Review
- Combining CRISPRi and metabolomics for functional annotation of compound libraries.Nature chemical biology · 2022Article
- Mechanisms Underlying Synergistic Killing of Polymyxin B in Combination with Cannabidiol againstPharmaceutics · 2022Article
- Integration of Transcriptomics Data and Metabolomic Data Using Biomedical Literature Mining and Pathway Analysis.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Metabolomics Insights into Chemical Convergence inMetabolites · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Deciphering the mode of action (MOA) of new antibiotics discovered through phenotypic screening is of increasing importance. Metabolomics offers a potentially rapid and cost-effective means of identifying modes of action of drugs whose effects are mediated through changes in metabolism. Metabolomics techniques also collect data on off-target effects and drug modifications. Here, we present data from an untargeted liquid chromatography-mass spectrometry approach to identify the modes of action of eight compounds: 1-[3-fluoro-4-(5-methyl-2,4-dioxo-pyrimidin-1-yl)phenyl]-3-[2-(trifluoromethyl)phenyl]urea (AZ1), 2-(cyclobutylmethoxy)-5'-deoxyadenosine, triclosan, fosmidomycin, CHIR-090, carbonyl cyanidem-chlorophenylhydrazone (CCCP), 5-chloro-2-(methylsulfonyl)-N-(1,3-thiazol-2-yl)-4-pyrimidinecarboxamide (AZ7), and ceftazidime. Data analysts were blind to the compound identities but managed to identify the target as thymidylate kinase for AZ1, isoprenoid biosynthesis for fosmidomycin, acyl-transferase for CHIR-090, and DNA metabolism for 2-(cyclobutylmethoxy)-5'-deoxyadenosine. Changes to cell wall metabolites were seen in ceftazidime treatments, although other changes, presumably relating to off-target effects, dominated spectral outputs in the untargeted approach. Drugs which do not work through metabolic pathways, such as the proton carrier CCCP, have no discernible impact on the metabolome. The untargeted metabolomics approach also revealed modifications to two compounds, namely, fosmidomycin and AZ7. An untreated control was also analyzed, and changes to the metabolome were seen over 4 h, highlighting the necessity for careful controls in these types of studies. Metabolomics is a useful tool in the analysis of drug modes of action and can complement other technologies already in use.
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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.