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Chem Phys Lipids. 2010 Feb;163(2):131-40. doi: 10.1016/j.chemphyslip.2009.10.006. Epub 2009 Oct 31.

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.

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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.


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.

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