Binding interactions of bacterial lipopolysaccharide and the cationic amphiphilic peptides polymyxin B and WLBU2.

Binding interactions of bacterial lipopolysaccharide and the cationic amphiphilic peptides polymyxin B and WLBU2.
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DOI:
10.1016/j.colsurfb.2014.05.004
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发表时间:
2014-08-01
影响因子:
5.8
通讯作者:
Schilke, Karl F.
Schilke, Karl F.
中科院分区:
工程技术2区
文献类型:
--
作者:
Ryder, Matthew P.;Wu, Xiangming;McKelvey, Greg R.;McGuire, Joseph;Schilke, Karl F.

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血液通过吸附装置,通过与固定的、膜活性的、杀菌肽的特异性结合来去除细菌和内毒素,这有望用于治疗严重的血液感染。肽插入靶膜和快速/强结合是期望的,而膜破坏和降解产物向循环血液的释放不是期望的。在这里,我们描述了细菌内毒素(脂多糖,LPS)和膜活性杀菌肽WLBU 2和多粘菌素B(Pm B)之间的相互作用。使用空气-水界面张力计和光波导光模式光谱法分析LPS和肽的混合物的界面行为强烈表明插入完整的LPS囊泡的肽WLBU 2没有囊泡不稳定。相反,动态光散射(DLS)的研究表明,LPS囊泡似乎经历肽诱导的PmB的存在下不稳定。圆二色谱进一步证实,WLBU 2,这表明在水溶液中的无序结构和基本上在膜模拟环境中的螺旋结构,是稳定地位于LPS膜内的肽囊泡混合物。因此,我们预期,如果以保持其移动性和溶剂可及性的方式拴系,则在界面处呈现WLBU 2将能够捕获细菌和内毒素,而不会促进内毒素重新引入循环血液,从而使不良临床结果最小化。另一方面,我们的结果表明LPS与多粘菌素B的相互作用没有这样有利的结果。
Passage of blood through a sorbent device for removal of bacteria and endotoxin by specific binding with immobilized, membrane-active, bactericidal peptides holds promise for treating severe blood infections. Peptide insertion in the target membrane and rapid/strong binding is desirable, while membrane disruption and release of degradation products to the circulating blood is not. Here we describe interactions between bacterial endotoxin (lipopolysaccharide, LPS) and the membrane-active, bactericidal peptides WLBU2 and polymyxin B (PmB). Analysis of the interfacial behavior of mixtures of LPS and peptide using air-water interfacial tensiometry and optical waveguide lightmode spectroscopy strongly suggests insertion of intact LPS vesicles by the peptide WLBU2 without vesicle destabilization. In contrast, dynamic light scattering (DLS) studies show that LPS vesicles appear to undergo peptide-induced destabilization in the presence of PmB. Circular dichroism spectra further confirm that WLBU2, which shows disordered structure in aqueous solution and substantially helical structure in membrane-mimetic environments, is stably located within the LPS membrane in peptide-vesicle mixtures. We therefore expect that presentation of WLBU2 at an interface, if tethered in a fashion which preserves its mobility and solvent accessibility, will enable the capture of bacteria and endotoxin without promoting reintroduction of endotoxin to the circulating blood, thus minimizing adverse clinical outcomes. On the other hand, our results suggest no such favorable outcome of LPS interactions with polymyxin B.
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