Hanna Sylvia L, Huang Jenny L, Swinton Alana J, Caputo Gregory A, Vaden Timothy D
Department of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, United States.
Department of Chemistry and Biochemistry, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, United States; Department of Biomedical and Translational Sciences, Rowan University, 201 Mullica Hill Road, Glassboro, NJ 08028, United States.
Biophys Chem. 2017 Aug;227:1-7. doi: 10.1016/j.bpc.2017.05.002. Epub 2017 May 11.
Ionic liquids (ILs) have been investigated for potential antibacterial and antibiotic applications due to their ability to destabilize and permeabilize the lipid bilayers in cell membranes. Bacterial assays have shown that combining ILs with antibiotics can provide a synergistic enhancement of their antibacterial activities. We have characterized the mechanism by which the conventional ILs 1-butyl-3-methylimidazolium chloride (BMICl) and 1-butyl-3-methylimidazolium tetrafluoroborate (BMIBF) enhance the lipid membrane permeabilization of the well-known antibiotic polymyxin B (PMB). We studied the sizes and membrane permeabilities of multilamellar and unilamellar lipid bilayer vesicles in the presence of ILs alone in aqueous solution, PMB alone, and ILs combined together with PMB. Light scattering-based experiments show that vesicle sizes dramatically increase when ILs are combined with PMB, which suggests that the materials combine to synergistically enhance lipid membrane disruption leading to vesicle aggregation. Lipid bilayer leakage experiments using tris (2,2'-bipyridyl) ruthenium (II) (Ru(bpy)) trapped in lipid vesicles, in which the trapped Ru(bpy) fluorescence lifetime increases when it leaks out of the vesicle, show that combining BMIBF and PMB together permeabilize the membrane significantly more than with PMB or the IL alone. This demonstrates that ILs can assist in antibiotic permeabilization of lipid bilayers which could explain the increased antibiotic activities in the presence of ILs in solution.
离子液体（ILs）因其能够破坏细胞膜中的脂质双层并使其通透，而被研究用于潜在的抗菌和抗生素应用。细菌检测表明，将离子液体与抗生素结合可以协同增强它们的抗菌活性。我们已经表征了传统离子液体1-丁基-3-甲基咪唑氯盐（BMICl）和1-丁基-3-甲基咪唑四氟硼酸盐（BMIBF）增强著名抗生素多粘菌素B（PMB）脂质膜通透性的机制。我们研究了在水溶液中单独存在离子液体、单独存在PMB以及离子液体与PMB结合时多层和单层脂质双层囊泡的大小和膜通透性。基于光散射的实验表明，当离子液体与PMB结合时，囊泡大小会显著增加，这表明这些物质结合起来协同增强脂质膜破坏，导致囊泡聚集。使用包裹在脂质囊泡中的三（2,2'-联吡啶）钌（II）（Ru(bpy)）进行的脂质双层泄漏实验表明，当Ru(bpy)从囊泡中泄漏出来时其荧光寿命会增加，结果显示将BMIBF和PMB结合在一起时对膜的通透作用明显大于单独使用PMB或离子液体。这表明离子液体可以协助抗生素使脂质双层通透，这可以解释在溶液中存在离子液体时抗生素活性增加的现象。
