ArticleeLife2025
Daptomycin forms a stable complex with phosphatidylglycerol for selective uptake to bacterial membrane.
Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Antibiotic Resistance and the Return to a Pre-Antibiotic Era: A Critical Narrative Review of a Global Catastrophe.Biomedicines · 2026Review
- Polygenic, cell-envelope adaptations drive high-frequency daptomycin resistance inAntimicrobial agents and chemotherapy · 2026Article
- Bacterial cell envelope-targeting antibiotics.Nature reviews. Microbiology · 2026Review
- State of the Art of Cyclic Lipopeptide-Membrane Interactions: Pore Formation and Bilayer Permeability.Pharmaceutics · 2025Review
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Authors and funding
6 authors.
Funding
Abstract
Daptomycin is a potent lipopeptide antibiotic used in the treatment of life-threatening Gram-positive infections, but the molecular mechanism of its interaction with bacterial membrane remains unclear. Here, we show that this interaction is divided into two stages, of which the first is a fast and reversible binding of the drug to phospholipid membrane in milliseconds, and the second is a slow and irreversible insertion into membrane in minutes, only in the presence of the bacteria-specific lipid phosphatidylglycerol, to a saturating point where the ratio of the drug to phosphatidylglycerol is 1:2. Fluorescence-based titration showed that the antibiotic simultaneously binds two molecules of phosphatidylglycerol with a nanomolar binding affinity in the presence of calcium ion. The resulting stable complex is easily formed in a test tube and readily isolated from the membrane of drug-treated bacterial cells, strongly supporting a unique drug uptake mechanism in which daptomycin forms a stable multicomponent complex with calcium and phosphatidylglycerol. Revelation of this novel uptake mechanism provides fresh insights into the mode of action of daptomycin and paves the way to new strategies to attenuate resistance to the drug.
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Registered trials
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