Squalamine: An Appropriate Strategy against the Emergence of Multidrug Resistant Gram-Negative Bacteria?

Abstract

We reported that squalamine is a membrane-active molecule that targets the membrane integrity as demonstrated by the ATP release and dye entry. In this context, its activity may depend on the membrane lipid composition. This molecule shows a preserved activity against bacterial pathogens presenting a noticeable multi-resistance phenotype against antibiotics such as polymyxin B. In this context and because of its structure, action and its relative insensitivity to efflux resistance mechanisms, we have demonstrated that squalamine appears as an alternate way to combat MDR pathogens and by pass the gap regarding the failure of new active antibacterial molecules.

The ribotoxin deoxynivalenol affects the viability and functions of glial cells

“…Intracellular ATP content was measured using the luciferin-luciferase reaction (Salmi et al, 2008). Briefly, cells seeded onto 12-well plates were lysed by adding Triton X100 at a final concentration of 1%.…”

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

“…Effects of CTAB, PMB and SQ on bacterial and eukaryotic cell membrane integrity were investigated using the cell-impermeable DNA/RNA dye propidium iodide (Niven and Mulholland, 1998;Salmi et al, 2008a). Briefly, over-night bacterial suspension and eukaryotic cell suspension were centrifuged 10 min at 4000 × g and 500 × g, respectively.…”

“…Based on previous studies showing that divalent cations such as calcium and magnesium are able to inhibit CAA activity toward bacteria (Chen and Feingold, 1972;Salmi et al, 2008a;Savage et al, 2002;Sixl and Galla, 1981), we tested the effect of calcium chloride on membrane permeabilisation of E. coli, Wehi-231 and Wehi-231 + LPS cells by the three CAA at 160 M (Fig. 6).…”

“…The conserved cationic charge of CAAs allows them to bind to the anionic charge of lipopolysaccharide (LPS) and/or phosphatidylglycerol (PG) exposed at the surface of the bacterial membrane. Such electrostatic interactions, sufficient to cause the release of divalent cations, could explain the selectivity of CAAs for the bacterial membrane over the eukaryotic membrane mainly formed of neutral lipids at physiological pH (phosphatidylcholine and cholesterol) although negatively charged lipids and proteins are also represented (Salmi et al, 2008a;Savage et al, 2002).…”

“…Whereas the interaction of other CAAs with biological membranes has been the subject of numerous studies, particularly with polymyxin B (PMB) (Chen and Feingold, 1972;Clausell et al, 2004Clausell et al, , 2005Clausell et al, , 2007Hartmann et al, 1978;Katsu et al, 1984Katsu et al, , 2002Katz et al, 2003;Galla, 1981, 1982;Tsubery et al, 2000Tsubery et al, , 2001Tsubery et al, , 2002Wiese et al, 1998Wiese et al, , 2003, relatively little information is available regarding the interaction of SQ with cellular membranes (Chen et al, 2006;Salmi et al, 2008a;Selinsky et al, 1998Selinsky et al, , 2000.…”