Abstract
Amphiphilic aminoglycoside derivatives are promising new antibacterials active against Gram-negative bacteria such as Pseudomonas aeruginosa, including colistin resistant strains. In this study, we demonstrated that addition of cardiolipin to the culture medium delayed growth of P. aeruginosa, favored asymmetrical growth and enhanced the efficiency of a new amphiphilic aminoglycoside derivative, the 3',6-dinonylneamine. By using membrane models mimicking P. aeruginosa plasma membrane composition (POPE:POPG:CL), we demonstrated the ability of 3'6-dinonylneamine to induce changes in the biophysical properties of membrane model lipid systems in a cardiolipin dependent manner. These changes include an increased membrane permeability associated with a reduced hydration and a decreased ability of membrane to mix and fuse as shown by monitoring calcein release, Generalized Polarization of Laurdan and fluorescence dequenching of octadecyl rhodamine B, respectively. Altogether, results shed light on how cardiolipin may be critical for improving antibacterial action of new amphiphilic aminoglycoside derivatives.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Naphthylamine / analogs & derivatives
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2-Naphthylamine / chemistry
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Aminoglycosides / chemistry
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Aminoglycosides / pharmacology*
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology*
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Cardiolipins / chemistry
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Cardiolipins / metabolism*
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Cell Membrane Permeability / drug effects
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Cell Membrane Permeability / physiology
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Dose-Response Relationship, Drug
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Fluoresceins / chemistry
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Fluoresceins / metabolism
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Laurates / chemistry
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Membrane Fusion / physiology
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Phosphatidylethanolamines / chemistry
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Phosphatidylglycerols / chemistry
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Pseudomonas aeruginosa / drug effects*
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Pseudomonas aeruginosa / growth & development
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Pseudomonas aeruginosa / metabolism
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Pseudomonas aeruginosa / ultrastructure
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Unilamellar Liposomes / chemistry
Substances
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Aminoglycosides
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Anti-Bacterial Agents
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Cardiolipins
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Fluoresceins
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Laurates
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Phosphatidylethanolamines
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Phosphatidylglycerols
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Unilamellar Liposomes
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1-palmitoyl-2-oleoylphosphatidylethanolamine
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1-palmitoyl-2-oleoylglycero-3-phosphoglycerol
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2-Naphthylamine
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fluorexon
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laurdan
Grants and funding
This work was supported by the « Fonds National de la Recherche Scientifique » (3.4578.12, T.1003.14 and J.0205.16; MEK and JS) and by Fondation pour la Recherche Médicale (DBF20161136768; JK), SATT Linksium Grenoble Alpes and Programme Labex (ARCANE project ANR-11-LABX-003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.