PDF(Pubmed)
Abstract：
LL-37 is the only member of the cathelicidin-type host defense peptide family in humans. It exhibits broad-spectrum bactericidal activity, which represents a distinctive advantage for future therapeutic targets. The presence of choline in the growth medium for bacteria changes the composition and physicochemical properties of their membranes, which affects LL-37\'s activity as an antimicrobial agent. In this study, the effect of the LL-37 peptide on the phospholipid monolayers at the liquid-air interface imitating the membranes of Legionella gormanii bacteria was determined. The Langmuir monolayer technique was employed to prepare model membranes composed of individual classes of phospholipids-phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), cardiolipin (CL)-isolated from L. gormanii bacteria supplemented or non-supplemented with exogenous choline. Compression isotherms were obtained for the monolayers with or without the addition of the peptide to the subphase. Then, penetration tests were carried out for the phospholipid monolayers compressed to a surface pressure of 30 mN/m, followed by the insertion of the peptide into the subphase. Changes in the mean molecular area were observed over time. Our findings demonstrate the diversified effect of LL-37 on the phospholipid monolayers, depending on the bacteria growth conditions. The substantial changes in membrane properties due to its interactions with LL-37 enable us to propose a feasible mechanism of peptide action at a molecular level. This can be associated with the stable incorporation of the peptide inside the monolayer or with the disruption of the membrane leading to the removal (desorption) of molecules into the subphase. Understanding the role of antimicrobial peptides is crucial for the design and development of new strategies and routes for combating resistance to conventional antibiotics.
摘要：
LL-37是人类中唯一的cathelicidin型宿主防御肽家族成员。它具有广谱杀菌活性，这代表了未来治疗目标的独特优势。细菌生长培养基中胆碱的存在会改变其膜的组成和理化性质，这影响了LL-37作为抗菌剂的活性。在这项研究中,确定了LL-37肽对模仿军团菌gormanii细菌膜的液-气界面磷脂单层的影响。Langmuir单层技术用于制备由磷脂-磷脂酰胆碱（PC）的各个类别组成的模型膜，磷脂酰乙醇胺(PE),磷脂酰甘油（PG），心磷脂（CL）-从补充或未补充外源胆碱的戈尔曼乳杆菌中分离。在向亚相添加或不添加肽的情况下,获得单层的压缩等温线。然后，渗透测试进行了磷脂单层压缩到30mN/m的表面压力，然后将肽插入亚相。观察到平均分子面积随时间的变化。我们的发现证明了LL-37对磷脂单层的多样化作用，取决于细菌的生长条件。由于其与LL-37的相互作用而引起的膜特性的实质性变化使我们能够在分子水平上提出肽作用的可行机制。这可能与肽在单层内部的稳定掺入或与导致分子去除(解吸)进入亚相的膜破坏有关。了解抗菌肽的作用对于设计和开发对抗常规抗生素耐药性的新策略和途径至关重要。
