ArticleScientific reports2017
Untargeted metabolomics analysis reveals key pathways responsible for the synergistic killing of colistin and doripenem combination against Acinetobacter baumannii.
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 50 papers.
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Who cites it
50 citing papers in PubMed, 99 citations in OpenAlex.
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- Metabolic profiling unveils enhanced antibacterial synergy of polymyxin B and teixobactin against multi-drug resistant Acinetobacter baumannii.Scientific reports · 2024Article
- Combinations of Antibiotics Effective against Extensively- and Pandrug-ResistantMicroorganisms · 2024Article
- Providing insight into the mechanism of action of cationic lipidated oligomers using metabolomics.mSystems · 2024Article
- Identifying and mathematically modeling the time-course of extracellular metabolic markers associated with resistance to ceftolozane/tazobactam inAntimicrobial agents and chemotherapy · 2024Article
- Gut microbiome features and metabolites in non-alcoholic fatty liver disease among community-dwelling middle-aged and older adults.BMC medicine · 2024Article
- Acinetobacter Metabolism in Infection and Antimicrobial Resistance.Infection and immunity · 2023Review
- Exploring Synergistic Combinations in Extended and Pan-Drug Resistant (XDR and PDR) Whole Genome SequencedMicroorganisms · 2023Article
- A Bittersweet Kiss of Gram-Negative Bacteria: The Role of ADP-Heptose in the Pathogenesis of Infection.Microorganisms · 2023Review
- Gold(I) selenium N-heterocyclic carbene complexes as potent antibacterial agents against multidrug-resistant gram-negative bacteria via inhibiting thioredoxin reductase.Redox biology · 2023Article
- Combating Escherichia coli O157:H7 with Functionalized Chickpea-Derived Antimicrobial Peptides.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Sample Preparation in Microbial Metabolomics: Advances and Challenges.Advances in experimental medicine and biology · 2023Article
- Metabolomics revealed mechanism for the synergistic effect of sulbactam, polymyxin-B and amikacin combination againstFrontiers in microbiology · 2023Article
- Metabolic perturbations and key pathways associated with the bacteriostatic activity ofAccess microbiology · 2023Article
- Isotopic Tracer for Absolute Quantification of Metabolites of the Pentose Phosphate Pathway in Bacteria.Metabolites · 2022Review
- Integrated metabolomic and transcriptomic analyses of the synergistic effect of polymyxin-rifampicin combination against Pseudomonas aeruginosa.Journal of biomedical science · 2022Article
- OBIF: an omics-based interaction framework to reveal molecular drivers of synergy.NAR genomics and bioinformatics · 2022Article
- Bacterial Metabolomics: Sample Preparation Methods.Biochemistry research international · 2022Review
- Comparative metabolomics revealed key pathways associated with the synergistic killing of multidrug-resistantComputational and structural biotechnology journal · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Combination therapy is deployed for the treatment of multidrug-resistant Acinetobacter baumannii, as it can rapidly develop resistance to current antibiotics. This is the first study to investigate the synergistic effect of colistin/doripenem combination on the metabolome of A. baumannii. The metabolite levels were measured using LC-MS following treatment with colistin (2 mg/L) or doripenem (25 mg/L) alone, and their combination at 15 min, 1 hr and 4 hr (n = 4). Colistin caused early (15 min and 1 hr) disruption of the bacterial outer membrane and cell wall, as demonstrated by perturbation of glycerophospholipids and fatty acids. Concentrations of peptidoglycan biosynthesis metabolites decreased at 4 hr by doripenem alone, reflecting its mechanism of action. The combination induced significant changes to more key metabolic pathways relative to either monotherapy. Down-regulation of cell wall biosynthesis (via D-sedoheptulose 7-phosphate) and nucleotide metabolism (via D-ribose 5-phosphate) was associated with perturbations in the pentose phosphate pathway induced initially by colistin (15 min and 1 hr) and later by doripenem (4 hr). We discovered that the combination synergistically killed A. baumannii via time-dependent inhibition of different key metabolic pathways. Our study highlights the significant potential of systems pharmacology in elucidating the mechanism of synergy and optimizing antibiotic pharmacokinetics/pharmacodynamics.
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