Department of Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology, Ohlebergsweg 12, 35392 Giessen, Germany; LOEWE Centre for Translational Biodiversity Genomics (LOEWE-TBG), Senckenberganlage 25, 60325 Frankfurt, Germany.
Department of Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology, Ohlebergsweg 12, 35392 Giessen, Germany.
Toxicon. 2024 Aug 28;247:107810. doi: 10.1016/j.toxicon.2024.107810. Epub 2024 Jun 14.
Spider-derived peptides with insecticidal, antimicrobial and/or cytolytic activities, also known as spider venom antimicrobial peptides (AMPs), can be found in the venoms of RTA-clade spiders. They show translational potential as therapeutic leads. A set of 52 AMPs has been described in the Chinese wolf spider (Lycosa shansia), and many have been shown to exhibit antibacterial effects. Here we explored the potential to enhance their antimicrobial activity using bioengineering. We generated a panel of artificial derivatives of an A-family peptide and screened their activity against selected microbial pathogens, vertebrate cells and insects. In several cases, we increased the antimicrobial activity of the derivatives while retaining the low cytotoxicity of the parental molecule. Furthermore, we injected the peptides into adult Drosophila suzukii and found no evidence of insecticidal effects, confirming the low levels of toxicity. Our data therefore suggest that spider venom linear peptides naturally defend the venom gland against microbial colonization and can be modified into more potent antimicrobial agents that could help to battle infectious diseases in the future.
具有杀虫、抗菌和/或细胞溶解活性的蜘蛛衍生肽，也称为蜘蛛毒液抗菌肽 (AMPs)，可以在 RTA 类蜘蛛的毒液中找到。它们具有作为治疗先导物的转化潜力。在中国狼蛛 (Lycosa shansia) 中已经描述了一组 52 种 AMPs，其中许多 AMPs 已被证明具有抗菌作用。在这里，我们探索了使用生物工程增强其抗菌活性的潜力。我们生成了一组 A 族肽的人工衍生物，并筛选了它们对选定的微生物病原体、脊椎动物细胞和昆虫的活性。在几种情况下，我们在保留母体分子低细胞毒性的同时提高了衍生物的抗菌活性。此外，我们将肽注入成年果蝇体内，没有发现杀虫作用的证据，证实了低毒性。因此，我们的数据表明，蜘蛛毒液线性肽天然防御毒液腺免受微生物定植，并且可以被修饰成更有效的抗菌剂，这有助于未来对抗传染病。
