Abstract:
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.
摘要:
具有杀虫作用的蜘蛛衍生肽,抗菌和/或细胞溶解活性,也被称为蜘蛛毒抗菌肽(AMPs),可以在RTA进化枝蜘蛛的毒液中找到。它们显示出作为治疗导联的翻译潜力。在中国狼蜘蛛(Lycosashansia)中描述了一组52个AMP,和许多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微生物活性的潜力。我们产生了一组A家族肽的人工衍生物,并筛选了它们针对选定的微生物病原体的活性,脊椎动物细胞和昆虫。在一些情况下,我们增加了衍生物的抗菌活性,同时保留了亲本分子的低细胞毒性。此外,我们将这些肽注射到成年果蝇中,没有发现杀虫作用的证据,确认毒性水平低。因此,我们的数据表明,蜘蛛毒液线性肽可以自然地保护毒腺免受微生物定植,并且可以被修饰成更有效的抗菌剂,可以帮助将来对抗传染病。