Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences , Wuhan, China.
Key Laboratory of Control of Quality and Safety for Aquatic Products, Ministry of Agriculture and Rural Affairs , Beijing, China.
Virulence. 2021 Dec;12(1):165-176. doi: 10.1080/21505594.2020.1867455.
() can cause a number of diseases in both human and animals. related infections in aquaculture cause severe economic losses every year throughout the world. The emergence of antibiotic resistance that is due to the abuse of antibiotics has limited the application of antibiotics. Thus, novel approaches are needed to combat with treatment failure of antibiotics caused by resistant bacterial strains. Aerolysin plays a critical role in the pathogenesis of and has been considered as a novel target for developing drugs based on anti-virulence strategies. Here, we reported that luteolin, a natural product with no anti- activity, could reduce aerolysin-induced hemolysis by inhibiting aerolysin activity. The binding mode was simulated by molecular docking and dynamics simulation. Then the main binding sites were confirmed by fluorescence quenching assays. We found that luteolin could hindered the formation of functional heptamer of aerolysin according to the results of the oligomerization assay. Moreover, luteolin could protect A549 cells from aerolysin mediated cell death and increase the survival rate of -infected channel catfish. These findings suggest a novel approach to developing drugs fighting against , and luteolin can be a promising drug candidate for treatment of -associated infections.
（）可以在人类和动物中引起许多疾病。水产养殖中的相关感染每年在全球范围内造成严重的经济损失。由于抗生素的滥用，抗生素耐药性的出现限制了抗生素的应用。因此，需要新的方法来对抗由于耐药菌株导致的抗生素治疗失败。溶细胞素在的发病机制中起着关键作用，并且已经被认为是基于抗毒力策略开发药物的新靶标。在这里，我们报道了芦丁，一种没有抗活性的天然产物，通过抑制溶细胞素活性来减少溶细胞素诱导的溶血。通过分子对接和动力学模拟模拟了结合模式。然后通过荧光猝灭实验证实了主要结合位点。根据寡聚化实验的结果，我们发现芦丁可以阻止溶细胞素功能七聚体的形成。此外，芦丁可以保护 A549 细胞免受溶细胞素介导的细胞死亡，并提高感染的斑点叉尾鮰的存活率。这些发现为开发对抗的药物提供了一种新方法，并且芦丁可能是治疗相关感染的有前途的药物候选物。
