ArticleBiochemical pharmacology2021
Comparative metabolomics reveals key pathways associated with the synergistic activity of polymyxin B and rifampicin combination against multidrug-resistant Acinetobacter baumannii.
Article in Biochemical pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 26 citations in OpenAlex.
- BamA as a next-generation antibacterial target: mechanistic insights, inhibitor landscape, and rational drug design strategies.RSC advances · 2026Review
- Article
- Synergistic activity of rifampicin and polymyxin B against intracellular Gram-negative ESKAPE pathogens involves bacterial membrane alterations and enhanced oxidative damages.Antimicrobial agents and chemotherapy · 2026Article
- Dietary energy and protein gradients drive metabolic adaptation in growing-finishing yaks on the Qinghai-Tibet plateau.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Flash optimization of drug combinations for Acinetobacter baumannii with IDentif.AI-AMR.npj antimicrobials and resistance · 2025Article
- Natural products: A potential immunomodulators against inflammatory-related diseases.Inflammopharmacology · 2024Review
- Deciphering Antibiotic-Targeted Metabolic Pathways inLife (Basel, Switzerland) · 2024Article
- Discovery of new quaternized norharmane dimers as potential anti-MRSA agents.Journal of advanced research · 2024Article
- Metabolomics unveil key pathways underlying the synergistic activities of aztreonam and avibactam against multidrug-resistant Escherichia coli.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2024Article
- A case of treatment for pulmonary infection caused by multidrug-resistantRespirology case reports · 2024Article
- Synergistic Activity and Mechanism of Sanguinarine with Polymyxin B against Gram-Negative Bacterial Infections.Pharmaceutics · 2024Article
- Polymyxins: recent advances and challenges.Frontiers in pharmacology · 2024Review
- GATR-3, a Peptide That Eradicates Preformed Biofilms of Multidrug-ResistantAntibiotics (Basel, Switzerland) · 2023Article
- Computationally Designed AMPs with Antibacterial and Antibiofilm Activity against MDRAntibiotics (Basel, Switzerland) · 2023Article
- Model-informed dose optimisation of polymyxin-rifampicin combination therapy against multidrug-resistant Acinetobacter baumannii.International journal of antimicrobial agents · 2023Article
- Acinetobacter Metabolism in Infection and Antimicrobial Resistance.Infection and immunity · 2023Review
- Metabolic perturbations and key pathways associated with the bacteriostatic activity ofAccess microbiology · 2023Article
- Metabolomics revealed mechanism for the synergistic effect of sulbactam, polymyxin-B and amikacin combination againstFrontiers in microbiology · 2023Article
- Metabolomic and cultivation insights into the tolerance of the spacecraft-associatedFrontiers in microbiology · 2023Article
- Effects of amikacin, polymyxin-B, and sulbactam combination on the pharmacodynamic indices of mutant selection against multi-drug resistantFrontiers in microbiology · 2022Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Multidrug-resistant (MDR) Acinetobacter baumannii presents a critical challenge to human health worldwide and polymyxins are increasingly used as a last-line therapy. Due to the rapid emergence of resistance during polymyxin monotherapy, synergistic combinations (e.g. with rifampicin) are recommended to treat A. baumannii infections. However, most combination therapies are empirical, owing to a dearth of understanding on the mechanism of synergistic antibacterial killing. In the present study, we employed metabolomics to investigate the synergy mechanism of polymyxin B-rifampicin against A. baumannii AB5075, an MDR clinical isolate. The metabolomes of A. baumannii AB5075 were compared at 1 and 4 h following treatments with polymyxin B alone (0.75 mg/L, i.e. 3 × MIC), rifampicin alone (1 mg/L, i.e. 0.25 × MIC) and their combination. Polymyxin B monotherapy significantly perturbed glycerophospholipid and fatty acid metabolism at 1 h, reflecting its activity on bacterial outer membrane. Rifampicin monotherapy significantly perturbed glycerophospholipid, nucleotide and amino acid metabolism, which are related to the inhibition of RNA synthesis. The combination treatment significantly perturbed the metabolism of nucleotides, amino acids, fatty acids and glycerophospholipids at 1 and 4 h. Notably, the intermediate metabolite pools from pentose phosphate pathway were exclusively enhanced by the combination, while most metabolites from the nucleotide and amino acid biosynthesis pathways were significantly decreased. Overall, the synergistic activity of the combination was initially driven by polymyxin B which impacted pathways associated with outer membrane biogenesis; and subsequent effects were mainly attributed to rifampicin via the inhibition of RNA synthesis. This study is the first to reveal the synergistic killing mechanism of polymyxin-rifampicin combination against polymyxin-susceptible MDR A. baumannii at the network level. Our findings provide new mechanistic insights for optimizing this synergistic combination in patients.
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