Development of low-cost and eco-friendly approaches to fight bacterial pathogens is especially needed in aquaculture. We previously showed that exogenous malate reprograms zebrafish's metabolome to potentiate zebrafish survival against Vibrio alginolyticus infection. However, the underlying mechanism is unknown. Here, we use GC-MS based metabolomics to identify the malate-triggered metabolic shift. An activated TCA cycle and elevated taurine are identified as the key metabolic pathways and the most crucial biomarker of the reprogrammed metabolome, respectively. Taurine elevation is attributed to the activated TCA cycle, which is further supported by the increased expression of genes in the metabolic pathway of taurine biosynthesis from the isocitrate of the TCA cycle to taurine. Exogenous taurine increases the survival of zebrafish against V. alginolyticus infection as malate did. Moreover, exogenous taurine and malate regulate the expression of innate immunity genes and promote the generation of reactive oxygen species and nitrogen oxide in a similar way. The two metabolites can alleviate the excessive immune response to bacterial challenge, which protects fish from bacterial infection. These results indicate that malate enhances the survival of zebrafish to V. alginolyticus infection via taurine. Thus, our study highlights a metabolic approach to enhance a host's ability to fight bacterial infection.

中文翻译：

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苹果酸以与牛磺酸相同的方式提高了斑马鱼抵抗溶藻弧菌感染的存活率。

在水产养殖中特别需要开发低成本和生态友好的方法来对抗细菌病原体。我们以前表明，外源性苹果酸重编程了斑马鱼的代谢组，以增强斑马鱼抵抗溶藻弧菌感染的存活率。但是，其潜在机制尚不清楚。在这里，我们使用基于GC-MS的代谢组学来确定苹果酸触发的代谢变化。激活的TCA循环和牛磺酸升高被分别确定为重编程代谢组的关键代谢途径和最关键的生物标志物。牛磺酸的升高归因于激活的TCA循环，这由TCA循环的异柠檬酸到牛磺酸的牛磺酸生物合成代谢途径中基因表达的增加进一步支持。外源性牛磺酸可增加斑马鱼抗V的存活率。像苹果酸一样，溶藻性感染。此外，外源性牛磺酸和苹果酸以类似的方式调节先天免疫基因的表达并促进活性氧和氮氧化物的产生。这两种代谢物可以减轻对细菌攻击的过度免疫反应，从而保护鱼类免受细菌感染。这些结果表明苹果酸通过牛磺酸增强了斑马鱼对溶藻弧菌感染的存活。因此，我们的研究突出了一种代谢方法，以增强宿主抵抗细菌感染的能力。这两种代谢物可以减轻对细菌攻击的过度免疫反应，从而保护鱼类免受细菌感染。这些结果表明苹果酸通过牛磺酸增强了斑马鱼对溶藻弧菌感染的存活。因此，我们的研究强调了一种代谢方法，可以增强宿主抵抗细菌感染的能力。这两种代谢物可以减轻对细菌攻击的过度免疫反应，从而保护鱼类免受细菌感染。这些结果表明苹果酸通过牛磺酸增强了斑马鱼对溶藻弧菌感染的存活。因此，我们的研究突出了一种代谢方法，以增强宿主抵抗细菌感染的能力。