Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
School of Chemistry, Bio21 Institute, University of Melbourne, Melbourne, VIC 3010, Australia.
Biochim Biophys Acta Biomembr. 2018 Feb;1860(2):300-309. doi: 10.1016/j.bbamem.2017.10.007. Epub 2017 Oct 11.
Antimicrobial peptides (AMPs) interact directly with bacterial membrane lipids. Thus, changes in the lipid composition of bacterial membranes can have profound effects on the activity of AMPs. In order to understand the effect of bilayer thickness and molecular order on the activity of AMPs, the interaction of maculatin 1.1 (Mac1.1) with phosphatidylcholine (PC) model membranes composed of different monounsaturated acyl chain lengths between 14 and 22 carbons was characterised by dual polarisation interferometry (DPI) and 31P and 1H solid-state NMR techniques. The thickness and bilayer order of each PC bilayer showed a linear dependence on the acyl chain length. The binding of Mac1.1 exhibited a biphasic dependency between the amount of bound Mac1.1 and bilayer thickness, whereby the mass of bound peptide increased from C14 to C16 and then decreased from C16 to C22. Significant perturbation of 31P chemical shift anisotropy (CSA) values was only observed for DOPC (C18) and DEPC (C22), respectively. In the case of DEPC, the greater range in CSA indicated different headgroup conformations or environments in the presence of Mac1.1. Overall, the results indicated that there is a significant change in the bilayer order upon binding of Mac1.1 and this change occurred in a co-operative manner at higher concentrations of Mac1.1 with increasing bilayer thickness and order. Overall, an optimum bilayer thickness and lipid order may be required for effective membrane perturbation by Mac1.1 and increasing the bilayer thickness and order may counteract the activity of Mac1.1 and play a role in antimicrobial resistance to AMPs.
抗菌肽 (AMPs) 与细菌膜脂质直接相互作用。因此，细菌膜脂质组成的变化会对 AMPs 的活性产生深远影响。为了了解双层厚度和分子有序性对 AMPs 活性的影响，我们通过双偏振干涉测量 (DPI) 和 31P 和 1H 固态 NMR 技术研究了 Maculatin 1.1 (Mac1.1) 与不同单不饱和酰链长度为 14 至 22 个碳原子的磷脂酰胆碱 (PC) 模型膜之间的相互作用。每个 PC 双层的厚度和双层有序性与酰链长度呈线性关系。Mac1.1 的结合表现出与双层厚度之间的双相依赖性，其中结合的肽质量从 C14 增加到 C16，然后从 C16 减少到 C22。仅在 DOPC (C18) 和 DEPC (C22) 中观察到 31P 化学位移各向异性 (CSA) 值的显著扰动。在 DEPC 的情况下，更大的 CSA 范围表明在 Mac1.1 存在的情况下存在不同的头基构象或环境。总体而言，结果表明在 Mac1.1 结合时双层有序性发生了显著变化，并且这种变化以协同方式发生，随着双层厚度和有序性的增加，Mac1.1 的浓度也随之增加。总体而言，对于 Mac1.1 有效干扰膜，可能需要最佳的双层厚度和脂质有序性，并且增加双层厚度和有序性可能会抵消 Mac1.1 的活性，并在对抗 AMPs 的抗菌耐药性方面发挥作用。
