Laboratory of Phytopathology, Department of Plants and Crops, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium.
NMR and Structure Analysis Unit, Department of Organic and Macromolecular Chemistry, Faculty of Science, Ghent University, Krijgslaan 281, 9000 Ghent, Belgium.
Biochim Biophys Acta Biomembr. 2022 Oct 1;1864(10):184008. doi: 10.1016/j.bbamem.2022.184008. Epub 2022 Jul 19.
Cyclic lipopeptides (CLiPs) are secondary metabolites produced by a variety of bacteria. These compounds show a broad range of antimicrobial activities; therefore, they are studied for their potential applications in agriculture and medicine. It is generally assumed that the primary target of the CLiPs is the cellular membrane, where they can permeabilize the lipid bilayer. Model membrane systems are commonly used to investigate the effect of lipid composition on the permeabilizing activity of CLiPs, but these systems do not represent the full complexity of true biological membranes. Here, we introduce a novel method that uses sterol-auxotrophic oomycetes to investigate how the activity of membrane-active compounds is influenced by alterations in membrane sterol composition. More specifically, we investigated how ergosterol, cholesterol, beta-sitosterol and stigmasterol affect the activity of the structurally related Pseudomonas-derived CLiPs tolaasin and sessilin against the oomycete Pythium myriotylum. Both compounds were effective against oomycetes, although tolaasin was considerably more active. Interestingly, tolaasin and sessilin effects were similarly reduced by the presence of sterols, with cholesterol showing the highest reduction of activity.
环状脂肽 (CLiPs) 是多种细菌产生的次级代谢产物。这些化合物表现出广泛的抗菌活性; 因此，它们被研究用于农业和医学的潜在应用。一般认为，CLiPs 的主要靶标是细胞膜，在细胞膜中它们可以使脂质双层通透。模型膜系统常用于研究脂质组成对 CLiPs 通透活性的影响，但这些系统不能代表真正生物膜的全部复杂性。在这里，我们介绍了一种新方法，该方法使用甾醇营养缺陷型卵菌来研究膜活性化合物的活性如何受膜甾醇组成改变的影响。更具体地说，我们研究了麦角固醇、胆固醇、β-谷甾醇和豆甾醇如何影响结构相关的假单胞菌衍生的 CLiPs 托拉菌素和西西林对卵菌疫霉属的作用。这两种化合物对卵菌都有效，尽管托拉菌素的活性要高得多。有趣的是，甾醇的存在同样降低了托拉菌素和西西林的作用，其中胆固醇的活性降低幅度最大。
