Negatively Charged Lipids as a Potential Target for New Amphiphilic Aminoglycoside Antibiotics: A BIOPHYSICAL STUDY - Université de Lorraine Accéder directement au contenu
Article Dans Une Revue Journal of Biological Chemistry Année : 2016

Negatively Charged Lipids as a Potential Target for New Amphiphilic Aminoglycoside Antibiotics: A BIOPHYSICAL STUDY

Résumé

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.

Domaines

Chimie

Dates et versions

hal-01505211 , version 1 (11-04-2017)

Identifiants

Citer

Guillaume Sautrey, Micheline El Khoury, Andreia Giro Dos Santos, Louis Zimmermann, Magali Deleu, et al.. Negatively Charged Lipids as a Potential Target for New Amphiphilic Aminoglycoside Antibiotics: A BIOPHYSICAL STUDY. Journal of Biological Chemistry, 2016, 291 (26), pp.13864-13874. ⟨10.1074/jbc.M115.665364⟩. ⟨hal-01505211⟩
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