ArticleNature communications2024
Potent activity of polymyxin B is associated with long-lived super-stoichiometric accumulation mediated by weak-affinity binding to lipid A.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed.
- Membrane Disruption and Charge Neutralization Drive Synergy Between LL37-Derived Peptides and Polymyxins AgainstBiomolecules · 2026Article
- An LPS-Immobilized Affinity Screening Platform Identifies Lipopolysaccharide Binding Phytochemicals fromBiology · 2026Article
- Lipopolysaccharide hydrolysis-targeting nano-chimeras detoxify endotoxin through specific adsorption and efficient degradation.Nature communications · 2026Article
- Bacterial extracellular vesicles promote membrane repair and tolerance to polymyxin B.Science advances · 2026Article
- Bacterial cell envelope-targeting antibiotics.Nature reviews. Microbiology · 2026Review
- In vitro Screening for Synergistic Polymyxin B-Based Combinations Against KPC- Producing Carbapenem-ResistantDrug design, development and therapy · 2026Article
- An aryloxyphenol potentiates polymyxin against multidrug-resistantFrontiers in cellular and infection microbiology · 2026Article
- Modulation of LPS-associated virulence activity for reduction of periodontal inflammatory burden.Frontiers in microbiology · 2026Article
- Neutrophil-mediated delivery of hybrid cross-species nanovesicles for treatment of bacterial infections.Nature communications · 2025Article
- A lignan compound regulates LPS modifications via PmrA/B signaling cascades to potentiate colistin efficacy in vivo.PLoS pathogens · 2025Article
- Polymyxin B lethality requires energy-dependent outer membrane disruption.Nature microbiology · 2025Article
- A critical role forProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Lipopolysaccharide nanoparticles: A biomimetic platform to study bacterial surface.Biophysical journal · 2025Article
- Synergistic Antibacterial Activity of Amorolfine Combined with Colistin AgainstInternational journal of molecular sciences · 2025Article
- Depth-Resolved Temperature-Dependent Penetration of Polymyxin B in Phospholipids/Lipopolysaccharide Asymmetric Bilayers.ACS omega · 2025Article
- Unlocking the power of antimicrobial peptides: advances in production, optimization, and therapeutics.Frontiers in cellular and infection microbiology · 2025Review
- Development of polymyxin- and aminoglycoside-based outer membrane permeabilizers: a review.Frontiers in microbiology · 2025Review
- Antibiotic-mediated dysbiosis leads to activation of inflammatory pathways.Frontiers in immunology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polymyxins are gram-negative antibiotics that target lipid A, the conserved membrane anchor of lipopolysaccharide in the outer membrane. Despite their clinical importance, the molecular mechanisms underpinning polymyxin activity remain unresolved. Here, we use surface plasmon resonance to kinetically interrogate interactions between polymyxins and lipid A and derive a phenomenological model. Our analyses suggest a lipid A-catalyzed, three-state mechanism for polymyxins: transient binding, membrane insertion, and super-stoichiometric cluster accumulation with a long residence time. Accumulation also occurs for brevicidine, another lipid A-targeting antibacterial molecule. Lipid A modifications that impart polymyxin resistance and a non-bactericidal polymyxin derivative exhibit binding that does not evolve into long-lived species. We propose that transient binding to lipid A permeabilizes the outer membrane and cluster accumulation enables the bactericidal activity of polymyxins. These findings could establish a blueprint for discovery of lipid A-targeting antibiotics and provide a generalizable approach to study interactions with the gram-negative outer membrane.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.