ArticleThe Journal of antimicrobial chemotherapy2020
Lipid A profiling and metabolomics analysis of paired polymyxin-susceptible and -resistant MDR Klebsiella pneumoniae clinical isolates from the same patients before and after colistin treatment.
Article in The Journal of antimicrobial chemotherapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 31 citations in OpenAlex.
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- Label-Free Differentiation of Antimicrobial Resistance Groups Using Raman Spectroscopy.Analytical chemistry · 2026Article
- Serum proteomic profiling of sepsis patients reveals a protein-based diagnostic model, with metabolomic insights into carbapenem-resistantFrontiers in immunology · 2026Article
- Integrated Proteomics and Metabolomics Reveal Multifaceted Mechanisms of Colistin Resistance inInfection and drug resistance · 2026Article
- Emergence, Molecular Characteristics and Resistance Mechanisms of Colistin-ResistantInfection and drug resistance · 2025Article
- A novel small RNA PhaS contributes to polymyxin B-heteroresistance in carbapenem-resistantEmerging microbes & infections · 2024Article
- Article
- Lipid A Modification and Metabolic Adaptation in Polymyxin-Resistant, New Delhi Metallo-β-Lactamase-Producing Klebsiella pneumoniae.Microbiology spectrum · 2023Article
- Exogenous glutathione reverses meropenem resistance in carbapenem-resistantFrontiers in pharmacology · 2023Article
- Metabolic perturbations and key pathways associated with the bacteriostatic activity ofAccess microbiology · 2023Article
- A cyclic adenosine monophosphate response element-binding protein inhibitor enhances the antibacterial activity of polymyxin B by inhibiting the ATP hydrolyzation activity of CrrB.Frontiers in pharmacology · 2022Article
- Cell Membrane Remodeling Mediates Polymyxin B Resistance inFrontiers in microbiology · 2022Article
- Disulfiram Enhances the Activity of Polymyxin B AgainstInfection and drug resistance · 2022Article
- Polymyxin Triple Combinations against Polymyxin-Resistant, Multidrug-Resistant, KPC-Producing Klebsiella pneumoniae.Antimicrobial agents and chemotherapy · 2020Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundThe increased incidence of polymyxin-resistant MDR Klebsiella pneumoniae has become a major global health concern.
objectivesTo characterize the lipid A profiles and metabolome differences between paired polymyxin-susceptible and -resistant MDR K. pneumoniae clinical isolates.
methodsThree pairs of K. pneumoniae clinical isolates from the same patients were examined [ATH 7 (polymyxin B MIC 0.25 mg/L) versus ATH 8 (64 mg/L); ATH 15 (0.5 mg/L) versus ATH 16 (32 mg/L); and ATH 17 (0.5 mg/L) versus ATH 18 (64 mg/L)]. Lipid A and metabolomes were analysed using LC-MS and bioinformatic analysis was conducted.
resultsThe predominant species of lipid A in all three paired isolates were hexa-acylated and 4-amino-4-deoxy-l-arabinose-modified lipid A species were detected in the three polymyxin-resistant isolates. Significant metabolic differences were evident between the paired isolates. Compared with their corresponding polymyxin-susceptible isolates, the levels of metabolites in amino sugar metabolism (UDP-N-acetyl-α-d-glucosamine and UDP-N-α-acetyl-d-mannosaminuronate) and central carbon metabolism (e.g. pentose phosphate pathway and tricarboxylic acid cycle) were significantly reduced in all polymyxin-resistant isolates [fold change (FC) > 1.5, P < 0.05]. Similarly, nucleotides, amino acids and key metabolites in glycerophospholipid metabolism, namely sn-glycerol-3-phosphate and sn-glycero-3-phosphoethanolamine, were significantly reduced across all polymyxin-resistant isolates (FC > 1.5, P < 0.05) compared with polymyxin-susceptible isolates. However, higher glycerophospholipid levels were evident in polymyxin-resistant ATH 8 and ATH 16 (FC > 1.5, P < 0.05) compared with their corresponding susceptible isolates.
conclusionsTo our knowledge, this study is the first to reveal significant metabolic perturbations associated with polymyxin resistance in K. pneumoniae.
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