ArticleThe Journal of antimicrobial chemotherapy2019
Octapeptin C4 and polymyxin resistance occur via distinct pathways in an epidemic XDR Klebsiella pneumoniae ST258 isolate.
Article in The Journal of antimicrobial chemotherapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Rapid profiling of polymyxin B susceptibility in Gram-negative bacteria with a novel polymyxin-derived fluorescent probe.Journal of advanced research · 2026Article
- The colistin resistance pandemic: A dual threat from plasmid-encoded mobilised colistin resistance genes and chromosomal mutations.African journal of laboratory medicine · 2026Review
- Characterisation ofJAC-antimicrobial resistance · 2025Article
- Article
- Genomic Insights into Bacterial Resistance to Proline-Rich Antimicrobial Peptide Bac7.Membranes · 2023Article
- Review
- Characterization of Carbapenemase-ProducingAntibiotics (Basel, Switzerland) · 2022Article
- Bacterial signaling as an antimicrobial target.Current opinion in microbiology · 2020Review
- Overcoming Intrinsic and Acquired Resistance Mechanisms Associated with the Cell Wall of Gram-Negative Bacteria.Antibiotics (Basel, Switzerland) · 2020Review
- Colistin Heteroresistance among Extended Spectrum β-lactamases-ProducingMicroorganisms · 2020Article
- Predicting Phenotypic Polymyxin Resistance in Klebsiella pneumoniae through Machine Learning Analysis of Genomic Data.mSystems · 2020Article
- Regulating polymyxin resistance in Gram-negative bacteria: roles of two-component systems PhoPQ and PmrAB.Future microbiology · 2020Review
- Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPolymyxin B and E (colistin) have been pivotal in the treatment of XDR Gram-negative bacterial infections; however, resistance has emerged. A structurally related lipopeptide, octapeptin C4, has shown significant potency against XDR bacteria, including polymyxin-resistant strains, but its mode of action remains undefined.
objectivesWe sought to compare and contrast the acquisition of resistance in an XDR Klebsiella pneumoniae (ST258) clinical isolate in vitro with all three lipopeptides to potentially unveil variations in their mode of action.
methodsThe isolate was exposed to increasing concentrations of polymyxins and octapeptin C4 over 20 days. Day 20 strains underwent WGS, complementation assays, antimicrobial susceptibility testing and lipid A analysis.
resultsTwenty days of exposure to the polymyxins resulted in a 1000-fold increase in the MIC, whereas for octapeptin C4 a 4-fold increase was observed. There was no cross-resistance observed between the polymyxin- and octapeptin-resistant strains. Sequencing of polymyxin-resistant isolates revealed mutations in previously known resistance-associated genes, including crrB, mgrB, pmrB, phoPQ and yciM, along with novel mutations in qseC. Octapeptin C4-resistant isolates had mutations in mlaDF and pqiB, genes related to phospholipid transport. These genetic variations were reflected in distinct phenotypic changes to lipid A. Polymyxin-resistant isolates increased 4-amino-4-deoxyarabinose fortification of lipid A phosphate groups, whereas the lipid A of octapeptin C4-resistant strains harboured a higher abundance of hydroxymyristate and palmitoylate.
conclusionsOctapeptin C4 has a distinct mode of action compared with the polymyxins, highlighting its potential as a future therapeutic agent to combat the increasing threat of XDR bacteria.
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