ArticleAntimicrobial agents and chemotherapy2011
Reduction in membrane phosphatidylglycerol content leads to daptomycin resistance in Bacillus subtilis.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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79 citing papers in PubMed, 147 citations in OpenAlex.
- Saturated fatty acids enhance daptomycin activity in a Fak-dependent manner in enterococci.Microbiology (Reading, England) · 2026Article
- 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
- From Membrane Composition to Antimicrobial Strategies: Experimental and Computational Approaches to AMP Design and Selectivity.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- The last resort antibiotic daptomycin exhibits two independent antibacterial mechanisms of action.Nature communications · 2025Article
- Daptomycin forms a stable complex with phosphatidylglycerol for selective uptake to bacterial membrane.eLife · 2025Article
- Antibiotic Resistance Gene Expression in Veterinary Probiotics: Two Sides of the Coin.Veterinary sciences · 2025Review
- Molecular basis of cell membrane adaptation in daptomycin-resistant Enterococcus faecalis.JCI insight · 2024Article
- Overexpression of diglucosyldiacylglycerol synthase leads to daptomycin resistance inJournal of bacteriology · 2024Article
- Comprehensive Metagenomic Analysis of Veterinary Probiotics in Broiler Chickens.Animals : an open access journal from MDPI · 2024Article
- DefectivemSphere · 2024Article
- Defective pgsA contributes to increased membrane fluidity and cell wall thickening in S. aureus with high-level daptomycin resistance.bioRxiv : the preprint server for biology · 2024Article
- From the outer space to the inner cell: deconvoluting the complexity ofMicrobiology spectrum · 2024Article
- Identification ofJournal of bacteriology · 2024Article
- Gram-Positive Bacterial Membrane-Based Biosensor for Multimodal Investigation of Membrane-Antibiotic Interactions.Biosensors · 2024Article
- Rising prevalence and drug resistance ofFrontiers in cellular and infection microbiology · 2024Review
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- Investigating Daptomycin-Membrane Interactions Using Native MS and Fast Photochemical Oxidation of Peptides in Nanodiscs.Analytical chemistry · 2023Article
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19 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Daptomycin (DAP) is a cyclic lipopeptide that disrupts the functional integrity of the cell membranes of Gram-positive bacteria in a Ca(2+)-dependent manner. Here we present genetic, genomic, and phenotypic analyses of an evolved DAP-resistant isolate, Dap(R)1, from the model bacterium Bacillus subtilis 168. Dap(R)1 was obtained by serial passages with increasing DAP concentrations, is 30-fold more resistant than the parent strain, and displays cross-resistance to vancomycin, moenomycin, and bacitracin. Dap(R)1 is characterized by aberrant septum placement, notably thickened peptidoglycan at the cell poles, and pleiotropic alterations at both the transcriptome and proteome levels. Genome sequencing of Dap(R)1 revealed 44 point mutations, 31 of which change protein sequences. An intermediate isolate that was 20-fold more resistant to DAP than the wild type had only three of these point mutations: mutations affecting the cell shape modulator gene mreB, the stringent response gene relA, and the phosphatidylglycerol synthase gene pgsA. Genetic reconstruction studies indicated that the pgsA(A64V) allele is primarily responsible for DAP resistance. Allelic replacement with wild-type pgsA restored DAP sensitivity to wild-type levels. The additional point mutations in the evolved strain may contribute further to DAP resistance, serve to compensate for the deleterious effects of altered membrane composition, or represent neutral changes. These results suggest a resistance mechanism by which reduced levels of phosphatidylglycerol decrease the net negative charge of the membrane, thereby weakening interaction with the positively charged Ca(2+)-DAP complex.
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Registered trials
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