Molecular mechanisms of polymyxin B Membrane interactions:: Direct correlation between surface charge density and self-promoted transport
Molecular mechanisms of polymyxin B Membrane interactions:: Direct correlation between surface charge density and self-promoted transport
复制标题
DOI：
10.1007/s002329900350
复制
发表时间：
1998-03-15
影响因子：
2.4
通讯作者：
Seydel, U
中科院分区：
文献类型：
--
作者：
Wiese, A;Münstermann, M;Seydel, U
我们通过电学测量研究了聚阳离子肽抗生素多粘菌素B（PMB）与不对称平面双层膜的相互作用。双层的不同组合物，包括各种革兰氏阴性菌的外膜的脂质基质。代表细菌内小叶的一个小叶由磷脂混合物（PL;磷脂酰乙醇胺、β-甘油和二磷脂酰甘油，摩尔比为81：17：2）组成。另一个（外）瓣叶由PMB敏感（大肠杆菌F515）或耐药菌株（奇异变形杆菌R45）的深层粗糙突变体的脂多糖（LPS）、少动鞘氨醇单胞菌IAM 12576的鞘糖脂（GSL-1）或磷脂（磷脂酰甘油、二植烷酰磷脂酰胆碱）组成。在所有的膜系统中，除了PMB的外叶导致诱导电流波动，由于短暂的膜病变。诱导病变所需的最小PMB浓度及其大小与脂质分子的电荷相关。在类似于PMB敏感菌株（F515 LPS/PL）的脂质基质的膜系统中，病变的直径足够大（d = 2.4 nm +/-8%）以允许PMB分子渗透（自促进运输），但在所有其他系统中它们太小。这些现象与洗涤剂（dodecyltriphenylphosphonium bromide，dodecyltrimethylammonium bromide，sodiumdodecylsulfate）引起的膜效应的比较揭示了类似洗涤剂的PMB-膜相互作用机制。
We have studied the interaction of the polycationic peptide antibiotic polymyxin B (PMB) with asymmetric planar bilayer membranes via electrical measurements. The bilayers were of different compositions, including those of the lipid matrices of the outer membranes of various species of Gram-negative bacteria. One leaflet, representing the bacterial inner leaflet, consisted of a phospholipid mixture (PL; phosphatidylethanolamine, -glycerol, and diphosphatidylglycerol in a molar ratio of 81:17:2). The other (outer) leaflet consisted either of lipopolysaccharide (LPS) from deep rough mutants of PMB-sensitive (Escherichia coli F515) or -resistant strains (Proteus mirabibis R45), glycosphingolipid (GSL-1) from Sphingomonas paucimobilis IAM 12576, or phospholipids (phosphatidylglycerol, diphytanoyl-phosphatidylcholine). In all membrane systems, the addition of PMB to the outer leaflet led to the induction of current fluctuations due to transient membrane lesions. The minimal PMB concentration required for the induction of the lesions and their size correlated with the charge of the lipid molecules. In the membrane system resembling the lipid matrix of a PMB-sensitive strain (F515 LPS/PL), the diameters of the lesions were large enough (d = 2.4 nm +/- 8%) to allow PMB molecules to permeate (self-promoted transport), but in all other systems they were too small. A comparison of these phenomena with membrane effects induced by detergents (dodecyltriphenylphosphonium bromide, dodecyltrimethylammonium bromide, sodiumdodecylsulfate) revealed a detergent-like mechanism of the PMB-membrane interaction.