Biophysical characterization of polymyxin b interaction with LPS aggregates and membrane model systems
Biophysical characterization of polymyxin b interaction with LPS aggregates and membrane model systems
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DOI：
10.1002/bip.22095
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发表时间：
2012-01-01
期刊：
影响因子：
2.9
通讯作者：
Santos, Nuno C.
中科院分区：
文献类型：
--
作者：
Domingues, Marco M.;Inacio, Rita G.;Santos, Nuno C.
抗生素耐药性是一个日益严重的健康问题。由于抗菌肽具有较低的细菌耐药性，因此正在开发抗菌肽以克服这一问题。多粘菌素B是一种对革兰氏阴性菌具有高亲和力的抗菌肽。本工作的目的是揭示多粘菌素B的LPS中和和杀菌活性的机制。通过动态光散射，我们观察到多粘菌素B以浓度依赖的方式诱导LPS聚集。正如ζ电位测量所揭示的那样，肽增加了LPS和膜模型系统的表面电荷。在带负电荷的POPG膜存在时，检测到较高的ζ电位变化。这种与带负电荷的膜（由POPG制成）的高相互作用，在更高的肽浓度下，随后发生膜渗透作用。两性离子型POPC膜的漏膜率较高。肽促进LPS聚集可能与血流中LPS的清除有关，最终通过促进巨噬细胞吞噬和/或阻断LPS与其受体的结合。我们的数据表明，多粘菌素B在分子水平上的作用机制涉及静电接近LPS的第一步；然后，它可能被内化并结合到细菌富含磷脂酰甘油的膜小叶上，在较高的肽浓度下诱导渗漏。(C) 2012.高分子材料工程学报（自然科学版），32(3):344 -344,2012。
Antibiotic resistance is an increasingly severe health problem. Antimicrobial peptides (AMPs) are being developed in order to overcome this problem, due to their lower bacterial resistance. Polymyxin B is an AMP with bactericidal effect on Gram-negative bacteria due to its high affinity for lipopolysaccharide (LPS). The objective of this work was to unravel the polymyxin B mechanisms of LPS neutralization and bactericidal activity. Using dynamic light scattering, it was observed that polymyxin B induces LPS aggregation in a concentration-dependent manner. The peptide increases the surface charge of LPS and membrane model systems, as revealed by zeta-potential measurements. The higher zeta-potential variations were detected in the presence of the negatively charged POPG membranes. This higher interaction with negatively charged membranes, made of POPG, was followed at higher peptide concentration by membrane permeabilization. Also, for zwitterionic POPC membranes a higher membrane leakage was detected. The peptide promotion of LPS aggregation may be related with the clearance of LPS from the bloodstream, eventually by facilitating macrophage phagocytosis and/or blocking the binding of LPS to its receptor. Our data indicate that polymyxin B mechanism of action at the molecular level involves a first step of electrostatic approach toward LPS; then, it may be internalized and bind to the bacterial phosphatidylglycerol-rich membrane leaflets, inducing leakage at higher peptide concentrations. (C) 2012 Wiley Periodicals, Inc.Biopolymers (Pept Sci) 98: 338-344, 2012.