Table_4_Temperature induces metabolic reprogramming in fish during bacterial infection.xlsx

Water temperature elevation as a consequence of global warming results in increased incidence of bacterial disease, such as edwardsiellosis, in fish farming. Edwardsiellosis is caused by the bacterial pathogen Edwardsiella tarda and affects many farmed fish including flounder (Paralichthys olivaceus). Currently, the effect of temperature on the metabolic response of flounder to E. tarda infection is unclear. In this study, we found that compared to low temperature (15°C), high temperature (23°C) enhanced E. tarda dissemination in flounder tissues. To examine the impact of temperature on the metabolism of flounder induced by E. tarda, comparative metabolomics were performed, which identified a large number of metabolites responsive to E. tarda invasion and temperature alteration. During E. tarda infection, the metabolic profile induced by elevated temperature was mainly featured by extensively decreased amino acids and TCA intermediates such as succinate, a proven immune regulator. Further, 38 potential metabolite markers of temperature effect (MMTE) in association with bacterial infection were identified. When used as exogenous supplements, two of the MMTE, i.e., L-methionine and UDP-glucose, effectively upregulated the expression of pro-inflammatory cytokines and suppressed E. tarda infection in flounder leukocytes. Taken together, the results of this study indicate an important influence of temperature on the metabolism of flounder during bacterial infection, which eventually affects the survivability of the fish.

全球变暖引发的水体温度升高，会使水产养殖中的细菌性疾病发病率升高，例如爱德华氏菌病（edwardsiellosis）。爱德华氏菌病由病原菌迟钝爱德华氏菌（Edwardsiella tarda）引发，可感染多种养殖鱼类，其中包括褐牙鲆（Paralichthys olivaceus）。目前，温度对褐牙鲆受迟钝爱德华氏菌感染时的代谢应答的影响尚不明确。本研究发现，相较于低温环境（15℃），高温环境（23℃）会增强迟钝爱德华氏菌在褐牙鲆组织中的播散能力。为探究温度对迟钝爱德华氏菌诱导的褐牙鲆代谢的影响，本研究开展了比较代谢组学分析，共鉴定出大量对迟钝爱德华氏菌侵染及温度变化产生应答的代谢物。在迟钝爱德华氏菌侵染过程中，高温诱导的代谢谱主要表现为氨基酸及三羧酸循环（TCA）中间产物（如琥珀酸——一种已被证实的免疫调节因子）的广泛下调。此外，本研究共鉴定出38个与细菌感染相关的温度效应潜在代谢物标志物（metabolite markers of temperature effect, MMTE）。将其中两种MMTE——即L-甲硫氨酸与尿苷二磷酸葡萄糖（UDP-glucose）——作为外源补充物添加后，可有效上调促炎细胞因子的表达，并在褐牙鲆白细胞中抑制迟钝爱德华氏菌的侵染。综上，本研究结果表明，温度在细菌感染期间对褐牙鲆的代谢具有重要调控作用，这最终会影响鱼类的生存能力。