title: Biophysical studies of the interaction of squalamine and other cationic amphiphilic molecules with bacterial and eukaryotic membranes: importance of the distribution coefficient in membrane selectivity.
abstract: The interaction of squalamine (SQ) with eukaryotic and prokaryotic membranes was studied and compared with the interaction of two other cationic amphipathic antimicrobials (CAAs), i.e. the antibiotic polymyxin B (PMB) and the detergent hexadecyltrimethylammonium bromide (CTAB). Whole cell experiments showed that the three CAA have in common the ability to interact with lipopolysaccharide-containing membranes through a divalent cation sensitive process. Differences were found regarding their kinetics of membrane permeabilisation and their selectivity for bacteria, with a preferential permeabilisation of bacteria by PMB>SQ and no selectivity for CTAB. Experiments with lipid monolayers and bilayers showed that this selectivity did not correlate with a preferential interaction of the CAAs with lipids but rather relies on differences in their ability to penetrate lipid bilayers and to cause electrically active lesions. Incidentally, our results also suggest that the distribution coefficient of CAAs could be used to predict their selectivity for bacteria.
authors.affiliation: Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille (CRN2M), University of Aix-Marseille 2 and Aix-Marseille 3, CNRS UMR 6231, INRA USC 2027, Faculté des Sciences de St-Jérôme, Laboratoire des Interactions Moléculaires et Systèmes Membranaires, 13013 Marseille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Di Pasquale
authors.forename: Chanaz
authors.initials: C
authors.lastname: Salmi-Smail
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Brunel
authors.forename: Patrick
authors.initials: P
authors.lastname: Sanchez
authors.forename: Jacques
authors.initials: J
authors.lastname: Fantini
authors.forename: Marc
authors.initials: M
authors.lastname: Maresca
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000737:chemistry / Q000494:pharmacology; D002777:Cholestanols / Q000737:chemistry / Q000494:pharmacology; D003902:Detergents / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D011112:Polymyxin B / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D002593:Cetrimonium Compounds; D002777:Cholestanols; D003902:Detergents; D008051:Lipid Bilayers; D008070:Lipopolysaccharides; C079655:squalamine; D011112:Polymyxin B; D002118:Calcium; D000077286:Cetrimonium