Boosted TCA cycle enhances survival of zebrafish to Vibrio alginolyticus infection.
Boosted TCA cycle enhances survival of zebrafish to Vibrio alginolyticus infection.
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增强的 TCA 循环可提高斑马鱼对溶藻弧菌感染的存活率
DOI：
10.1080/21505594.2017.1423188
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发表时间：
2018-01-01
期刊：
影响因子：
5.2
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Yang MJ;Cheng ZX;Jiang M;Zeng ZH;Peng B;Peng XX;Li H
摘要溶藻弧菌是一种可感染鱼类和人类的水媒病原菌，其暴发流行会给水产养殖业造成巨大的经济损失。因此，增强宿主从溶藻弧菌感染中存活的能力是对抗感染的关键，这仍然未被探索。本研究建立了溶藻弧菌-斑马鱼相互作用模型，探讨了斑马鱼在感染溶藻弧菌后的生存机制。我们使用基于GC-MS的代谢组学方法来表征感染后存活和死亡的斑马鱼之间的差异代谢组。模式识别分析确定三氯乙酸循环是受影响最大的途径。TCA循环中的代谢物在垂死的宿主中减少，而在存活的宿主中代谢物增加。此外，TCA循环中丙酮酸脱氢酶（PDH）、α-酮基谷氨酸脱氢酶（KGDH）和琥珀酸脱氢酶（SDH）的活性也支持了这一结论。在TCA循环中增加的代谢物中，苹果酸是鱼类存活的最关键生物标志物。事实上，外源性苹果酸以剂量依赖的方式促进斑马鱼的存活。相应的KGDH和SDH活性也有所提高。这些结果表明，TCA循环是负责响应溶藻弧菌引起的感染的存活或死亡的关键途径，并突出了发展代谢调节以控制感染的途径。
ABSTRACT Vibrio alginolyticus is a waterborne pathogen that infects a wide variety of hosts including fish and human, and the outbreak of this pathogen can cause a huge economic loss in aquaculture. Thus, enhancing host's capability to survive from V. alginolyticus infection is key to fighting infection and this remains still unexplored. In the present study, we established a V. alginolyticus-zebrafish interaction model by which we explored how zebrafish survived from V. alginolyticus infection. We used GC-MS based metabolomic approaches to characterize differential metabolomes between survival and dying zebrafish upon infection. Pattern recognition analysis identified the TCA cycle as the most impacted pathway. The metabolites in the TCA cycle were decreased in the dying host, whereas the metabolites were increased in the survival host. Furthermore, the enzymatic activities of the TCA cycle including pyruvate dehydrogenase (PDH), α-ketoglutaric dehydrogenase (KGDH) and succinate dehydrogenase (SDH) also supported this conclusion. Among the increased metabolites in the TCA cycle, malic acid was the most crucial biomarker for fish survival. Indeed, exogenous malate promoted zebrafish survival in a dose-dependent manner. The corresponding activities of KGDH and SDH were also increased. These results indicate that the TCA cycle is a key pathway responsible for the survival or death in response to infection caused by V. alginolyticus, and highlight the way on development of metabolic modulation to control the infection.
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