ABSTRACT

Aeromonas hydrophila (A. hydrophila) can cause a number of diseases in both human and animals. A. hydrophila-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 A. hydrophila 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-A. hydrophila 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 A. hydrophila-infected channel catfish. These findings suggest a novel approach to developing drugs fighting against A. hydrophila, and luteolin can be a promising drug candidate for treatment of A. hydrophila-associated infections.

摘要

嗜水气单胞菌( A.hydrophila ) 可引起人类和动物的多种疾病。A.水产养殖中的嗜水相关感染每年都会在全世界造成严重的经济损失。由于滥用抗生素而产生的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耐药菌株引起的抗生素治疗失败。气溶素扮演的发病机制中起关键作用嗜水和被认为是开发基于抗毒性药物战略的新靶点。在这里，我们报道了木犀草素，天然产品，没有抗嗜水气单活性，可以通过抑制 aerolysin 的活性来减少 aerolysin 引起的溶血。通过分子对接和动力学模拟来模拟结合模式。然后通过荧光猝灭测定确认主要结合位点。根据低聚测定的结果，我们发现木犀草素可以阻碍气溶素功能性七聚体的形成。此外，木犀草素可以保护气溶素介导的细胞死亡A549细胞，提高存活率嗜水气单感染的斑点叉尾鮰。这些结果表明一种新的方法来开发药物对抗战斗嗜水和木犀草素可以治疗的有希望的候选药物嗜水机相关感染。