title: Negatively Charged Lipids as a Potential Target for New Amphiphilic Aminoglycoside Antibiotics: A BIOPHYSICAL STUDY.
abstract: Bacterial membranes are highly organized, containing specific microdomains that facilitate distinct protein and lipid assemblies. Evidence suggests that cardiolipin molecules segregate into such microdomains, probably conferring a negative curvature to the inner plasma membrane during membrane fission upon cell division. 3',6-Dinonyl neamine is an amphiphilic aminoglycoside derivative active against Pseudomonas aeruginosa, including strains resistant to colistin. The mechanisms involved at the molecular level were identified using lipid models (large unilamellar vesicles, giant unilamelllar vesicles, and lipid monolayers) that mimic the inner membrane of P. aeruginosa The study demonstrated the interaction of 3',6-dinonyl neamine with cardiolipin and phosphatidylglycerol, two negatively charged lipids from inner bacterial membranes. This interaction induced membrane permeabilization and depolarization. Lateral segregation of cardiolipin and membrane hemifusion would be critical for explaining the effects induced on lipid membranes by amphiphilic aminoglycoside antibiotics. The findings contribute to an improved understanding of how amphiphilic aminoglycoside antibiotics that bind to negatively charged lipids like cardiolipin could be promising antibacterial compounds.
authors.affiliation: From the Université Catholique de Louvain, Louvain Drug Research Institute, Pharmacologie Cellulaire et Moléculaire, Avenue E. Mounier 73, UCL B1.73.05 Bruxelles, Belgium.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Sautrey
authors.affiliation: From the Université Catholique de Louvain, Louvain Drug Research Institute, Pharmacologie Cellulaire et Moléculaire, Avenue E. Mounier 73, UCL B1.73.05 Bruxelles, Belgium.
authors.forename: Micheline
authors.initials: M
authors.lastname: El Khoury
authors.affiliation: From the Université Catholique de Louvain, Louvain Drug Research Institute, Pharmacologie Cellulaire et Moléculaire, Avenue E. Mounier 73, UCL B1.73.05 Bruxelles, Belgium.
authors.forename: Andreia Giro
authors.initials: AG
authors.lastname: Dos Santos
authors.affiliation: the Département de Pharmacochimie Moléculaire, Université de Grenoble, Alpes/CNRS, UMR 5063, ICMG FR 2607, 470 Rue de la Chimie, BP 53, F-38041 Grenoble, France, and.
authors.forename: Louis
authors.initials: L
authors.lastname: Zimmermann
authors.affiliation: the Laboratoire de Biophysique Moleculaire aux Interfaces, Université de Liège, Gembloux Agro-Bio Tech, Passage des Déportés, 2, B-5030 Gembloux, Belgium.
authors.forename: Magali
authors.initials: M
authors.lastname: Deleu
authors.affiliation: the Laboratoire de Biophysique Moleculaire aux Interfaces, Université de Liège, Gembloux Agro-Bio Tech, Passage des Déportés, 2, B-5030 Gembloux, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Lins
authors.affiliation: the Département de Pharmacochimie Moléculaire, Université de Grenoble, Alpes/CNRS, UMR 5063, ICMG FR 2607, 470 Rue de la Chimie, BP 53, F-38041 Grenoble, France, and.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Décout
authors.affiliation: From the Université Catholique de Louvain, Louvain Drug Research Institute, Pharmacologie Cellulaire et Moléculaire, Avenue E. Mounier 73, UCL B1.73.05 Bruxelles, Belgium, marie-paule.mingeot@uclouvain.be.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Mingeot-Leclercq
mesh_terms: D002308:Cardiolipins / Q000737:chemistry*; D005601:Framycetin / Q000737:chemistry*; D010715:Phosphatidylglycerols / Q000737:chemistry*; D011550:Pseudomonas aeruginosa / Q000737:chemistry*
chemical_list: D002308:Cardiolipins; D010715:Phosphatidylglycerols; D005601:Framycetin; C488396:neamine
keywords: antibiotics; bacteria; cardiolipin; lipid bilayer; membrane lipid