State Key Laboratory of Bio-Control, School of Life Sciences, Sun Yat-sen University, Higher Education Mega Center, Guangzhou, 510630, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266071, China.
Faculty of Health Sciences, University of Macau, Macau.
Fish Shellfish Immunol. 2020 Feb;97:359-366. doi: 10.1016/j.fsi.2019.12.061. Epub 2019 Dec 19.
Bacterial infection severely impairs aquaculture development throughout the world. Despite the use of antibiotics to control bacterial infection, few other options are available especially in the area of complex ecosystem and various types of fish. In search for novel approaches in controlling bacterial infection, we adopt zebrafish, Danio reiro, as infection host and the bacteria, Vibrio alginolyticus, as pathogen to explore potential metabolites that boost host's capability to eliminate bacterial infection. By comparing the metabolome of dying fish, l-aspartic acid is a metabolite of differential abundance between the dying fish and surviving fish upon Vibrio alginolyticus infection. Exogenous l-aspartic acid increases fish survival rate from 46.67% to 76.67%. We further demonstrated that l-aspartic acid drives the production of nitrogen oxide that promotes phagocytosis. Whereas the inhibition of nitrogen oxide synthase would abolish l-aspartic acid-triggered phagocytosis as well as in vivo protective ability to V. alginolyticus. The importance of nitrogen oxide production in fish survival is also consistent with the observation in the dying fish that showed increased urea production but not nitrogen oxide. Thus, our results exemplify a novel approach in promoting fish survival in an eco-friendly way.
细菌感染严重阻碍了全球水产养殖业的发展。尽管抗生素被用于控制细菌感染，但在复杂生态系统和各种鱼类的领域，几乎没有其他选择。为了寻找控制细菌感染的新方法，我们采用斑马鱼（Danio reiro）作为感染宿主和弧菌（Vibrio alginolyticus）作为病原体，以探索增强宿主消除细菌感染能力的潜在代谢物。通过比较死亡鱼和存活鱼的代谢组学，发现 l-天冬氨酸是弧菌感染后死亡鱼和存活鱼之间差异丰度的代谢物。外源性 l-天冬氨酸将鱼的存活率从 46.67%提高到 76.67%。我们进一步证明，l-天冬氨酸驱动氮氧化物的产生，促进吞噬作用。而氮氧化物合酶的抑制作用会消除 l-天冬氨酸触发的吞噬作用以及对 V. alginolyticus 的体内保护能力。氮氧化物产生在鱼类存活中的重要性也与死亡鱼的观察结果一致，死亡鱼显示出尿素产生增加，但氮氧化物没有增加。因此，我们的结果例证了一种以生态友好的方式促进鱼类存活的新方法。
