Metabolic modulation of redox state confounds fish survival against Vibrio alginolyticus infection |
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Authors: | Qi-yang Gong Man-jun Yang Li-fen Yang Zhuang-gui Chen Ming Jiang Bo Peng |
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Institution: | 1. State Key Laboratory of Bio-Control, Guangdong Key Laboratory of Pharmaceutical Functional Genes School of Life Sciences, Center for Proteomics and Metabolomics, Sun Yat-sen University, Guangzhou, 510006 China
Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266071 China;2. State Key Laboratory of Bio-Control, Guangdong Key Laboratory of Pharmaceutical Functional Genes School of Life Sciences, Center for Proteomics and Metabolomics, Sun Yat-sen University, Guangzhou, 510006 China;3. Department of Pediatrics, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630 China |
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Abstract: | Vibrio alginolyticus threatens both humans and marine animals, but hosts respond to V. alginolyticus infection is not fully understood. Here, functional metabolomics was adopted to investigate the metabolic differences between the dying and surviving zebrafish upon V. alginolyticus infection. Tryptophan was identified as the most crucial metabolite, whose abundance was decreased in the dying group but increased in the survival group as compared to control group without infection. Concurrently, the dying zebrafish displayed excessive immune response and produced higher level of reactive oxygen species (ROS). Interestingly, exogenous tryptophan reverted dying rate through metabolome re-programming, thereby enhancing the survival from V. alginolyticus infection. It is preceded by the following mechanism: tryptophan fluxed into the glycolysis and tricarboxylic acid cycle (TCA cycle), promoted adenosine triphosphate (ATP) production and further increased the generation of NADPH. Meanwhile, tryptophan decreased NADPH oxidation. These together ameliorate ROS, key molecules in excessive immune response. This is further supported by the event that the inhibition of pyruvate metabolism and TCA cycle by inhibitors decreased D. reiro survival. Thus, our data indicate that tryptophan is a key metabolite for the host to fight against V. alginolyticus infection, representing an alternative strategy to treat bacterial infection in an antibiotic-independent way. |
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