Institut de Chimie UMR7177, CNRS, University of Strasbourg, 1, rue Blaise Pascal, 67000, Strasbourg, France.
J. Heyrovský Institute of Physical Chemistry, v.v.i, Czech Academy of Sciences, Dolejškova 2155/3, 182 23, Prague, Czech Republic.
Sci Rep. 2020 Jul 15;10(1):11652. doi: 10.1038/s41598-020-68416-1.
Magainin 2 and PGLa are cationic, amphipathic antimicrobial peptides which when added as equimolar mixture exhibit a pronounced synergism in both their antibacterial and pore-forming activities. Here we show for the first time that the peptides assemble into defined supramolecular structures along the membrane interface. The resulting mesophases are quantitatively described by state-of-the art fluorescence self-quenching and correlation spectroscopies. Notably, the synergistic behavior of magainin 2 and PGLa correlates with the formation of hetero-domains and an order-of-magnitude increased membrane affinity of both peptides. Enhanced membrane association of the peptide mixture is only observed in the presence of phophatidylethanolamines but not of phosphatidylcholines, lipids that dominate bacterial and eukaryotic membranes, respectively. Thereby the increased membrane-affinity of the peptide mixtures not only explains their synergistic antimicrobial activity, but at the same time provides a new concept to increase the therapeutic window of combinatorial drugs.
杀菌肽 2 和 PGLa 是阳离子、两亲性抗菌肽，当以等摩尔混合物形式添加时，其在抗菌和形成孔的活性方面表现出显著的协同作用。在这里，我们首次表明，这些肽沿膜界面组装成定义明确的超分子结构。通过最先进的荧光自猝灭和相关光谱学定量描述了所得中间相。值得注意的是，杀菌肽 2 和 PGLa 的协同行为与形成杂域以及两种肽的膜亲和力呈数量级增加相关。只有在存在磷酯酰乙醇胺而不是磷脂酰胆碱时才观察到肽混合物的增强的膜缔合，磷酯酰乙醇胺和磷脂酰胆碱分别是细菌和真核细胞膜的主要脂质。因此，肽混合物的增加的膜亲和力不仅解释了它们的协同抗菌活性，而且同时提供了增加组合药物治疗窗口的新概念。
