Department of Interfacial Phenomena, Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Skłodowska University, Maria Curie-Skłodowska Sq. 3, 20-031 Lublin, Poland.
Department of Genetics and Microbiology, Institute of Biological Sciences, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland.
Molecules. 2024 Mar 28;29(7):1522. doi: 10.3390/molecules29071522.
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 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 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.
LL-37 是人类唯一的抗菌肽家族成员。它具有广谱杀菌活性，这是未来治疗靶点的一个显著优势。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，从而影响 LL-37 作为抗菌剂的活性。在这项研究中，测定了 LL-37 肽对模拟细菌膜的液-气界面单层磷脂的影响。采用 Langmuir 单层技术制备由单个磷脂类组成的模型单层，包括从补充或不补充外源性胆碱的细菌中分离出的磷脂酰胆碱 (PC)、磷脂酰乙醇胺 (PE)、磷脂酰甘油 (PG) 和心磷脂 (CL)。对于加入或不加入肽的亚相获得了单层的压缩等温线。然后，对压缩至表面压力为 30 mN/m 的磷脂单层进行穿透试验，然后将肽插入亚相。观察到随时间的平均分子面积的变化。我们的研究结果表明，LL-37 对磷脂单层的影响具有多样性，这取决于细菌的生长条件。由于其与 LL-37 的相互作用，膜性质发生了实质性变化，这使我们能够在分子水平上提出一种可行的肽作用机制。这可能与肽在单层内的稳定掺入有关，或者与导致分子进入亚相的膜破坏（解吸）有关。了解抗菌肽的作用对于设计和开发新的策略和途径来对抗传统抗生素的耐药性至关重要。
