{"doi":"10.1093/jac/dkaa245","title":"Lipid A profiling and metabolomics analysis of paired polymyxin-susceptible and -resistant MDR <i>Klebsiella pneumoniae</i> clinical isolates from the same patients before and after colistin treatment","abstract":"BACKGROUND: The increased incidence of polymyxin-resistant MDR Klebsiella pneumoniae has become a major global health concern. OBJECTIVES: To characterize the lipid A profiles and metabolome differences between paired polymyxin-susceptible and -resistant MDR K. pneumoniae clinical isolates. METHODS: Three 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. RESULTS: The 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. CONCLUSIONS: To our knowledge, this study is the first to reveal significant metabolic perturbations associated with polymyxin resistance in K. pneumoniae.","journal":"Journal of Antimicrobial Chemotherapy","year":2020,"id":64432,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":33,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.5546,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":340484,"name":"Irene Galani","orcid":"0000-0001-6455-9848","position":1,"is_corresponding":false},{"id":321534,"name":"Mei‐Ling Han","orcid":"0000-0002-0861-2437","position":2,"is_corresponding":false},{"id":340485,"name":"Ilias Karaiskos","orcid":"0000-0002-2226-0239","position":3,"is_corresponding":false},{"id":304456,"name":"Darren J. Creek","orcid":"0000-0001-7497-7082","position":4,"is_corresponding":false},{"id":326950,"name":"Yan Zhu","orcid":"0000-0001-7342-3782","position":5,"is_corresponding":false},{"id":340486,"name":"Yu-Wei Lin","orcid":"0000-0001-7316-5293","position":6,"is_corresponding":false},{"id":326951,"name":"Tony Velkov","orcid":"0000-0002-0017-7952","position":7,"is_corresponding":false},{"id":340487,"name":"Helen Giamarellou","orcid":"0000-0002-7387-5065","position":8,"is_corresponding":false},{"id":258541,"name":"Jian Li","orcid":"0000-0001-7953-8230","position":9,"is_corresponding":false},{"id":341160,"name":"Su Mon Aye","orcid":null,"position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-18T21:12:32.635050Z","pmid":"32696049","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}