ArticleNature communications2025
The last resort antibiotic daptomycin exhibits two independent antibacterial mechanisms of action.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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.
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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.
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Who cites it
11 citing papers in PubMed.
- Effects of Cholesterol and Solution pH on Daptomycin-bilayer Interactions.The Journal of membrane biology · 2026Article
- Commonly prescribed medicines antagonise anti-MRSA antibiotics and select for resistance.Microbiology (Reading, England) · 2026Article
- Amylimycins A-C, New Bacillomycin D Analogs from Marine-DerivedMarine drugs · 2026Article
- Alanine Uptake Is Required to MaintainMicroorganisms · 2026Article
- Revealing the Fate of Isomeric Monounsaturated Fatty Acids inACS infectious diseases · 2026Article
- Host-driven remodelling of theMicrobiology (Reading, England) · 2026Review
- Lipid-donor-anchored genome mining uncovers dioxanopeptins, antibacterial lipopeptides with a 1,3-dioxane functionalized polyunsaturated lipid tail.Chemical science · 2026Article
- A two-component system signaling hub controls enterococcal membrane remodeling in response to daptomycin.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Targeting biofilm-driven antibiotic resistance: emerging mechanisms and next-generation therapeutic interventions.Frontiers in microbiology · 2026Review
- Resistance to last-resort antibiotics in enterococci.FEMS microbiology reviews · 2025Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Daptomycin is a lipopeptide antibiotic, commonly used as last resort treatment against multidrug resistant Gram-positive pathogens. Despite its clinical success, the mechanism through which daptomycin exerts its antibacterial properties has remained controversial. Much of the debate is focused around daptomycin's ability to depolarise the cytoplasmic membrane, potential formation of large membrane pores, and its more recently discovered capability to inhibit cell wall synthesis and disturb membrane lipid domain organisation through interactions with cell wall precursor lipids. Here we show that, rather than representing different facets of a single underlying activity, daptomycin exhibits two independent antibacterial mechanisms of action: (i) targeting of cell wall precursor lipids that leads to cell wall synthesis inhibition and (ii) membrane depolarisation that does not rely on interactions with cell wall precursor lipids. This dual mechanism of action provides an explanation for the frequently disagreeing findings obtained through in vivo and in vitro studies and explains why resistance development towards daptomycin is slow and multifactorial. In a broader context, this demonstrates that dual mechanism antibiotics can be clinically successful and exhibit favourable characteristics in terms of real-world, clinically relevant resistance development.
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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 OpenQuestion graph.