Edwardsiella tarda Tunes Tricarboxylic Acid Cycle to Evade Complement-Mediated Killing.
Edwardsiella tarda Tunes Tricarboxylic Acid Cycle to Evade Complement-Mediated Killing.
复制标题
迟缓爱德华氏菌调节三羧酸循环以逃避补体介导的杀伤
DOI：
10.3389/fimmu.2017.01706
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发表时间：
2017
影响因子：
7.3
通讯作者：
Peng B
中科院分区：
文献类型：
--
作者：
Cheng ZX;Gong QY;Wang Z;Chen ZG;Ye JZ;Li J;Wang J;Yang MJ;Ling XP;Peng B
逃避补体介导的杀伤是许多不同类型病原体的常见表型，但其机制仍知之甚少。迟缓爱德华氏菌是一种能感染人类和鱼类的重要病原体，其大多数临床分离株通常具有血清抗性。为探究潜在机制，我们采用基于气相色谱 - 质谱联用（GC - MS）的代谢组学方法，对迟缓爱德华氏菌EIB202在有或无血清胁迫条件下的代谢组进行分析。我们发现，在有血清存在时，三羧酸（TCA）循环显著增强。实时荧光定量PCR（qRT - PCR）和酶活性检测验证了这一结果。此外，促进TCA循环的外源性琥珀酸盐可增强血清抗性，而抑制TCA循环的TCA循环抑制剂（溴代丙酮酸和丙二酸）则会削弱血清抗性。而且，增强的TCA循环提高了膜电位，从而减少了细胞表面膜攻击复合物的形成，进而产生血清抗性。这些证据表明存在一种此前未知的依赖膜电位的血清抗性机制。因此，我们的研究结果揭示了病原体通过一种代谢策略来应对血清补体介导的杀伤。
Evasion of complement-mediated killing is a common phenotype for many different types of pathogens, but the mechanism is still poorly understood. Most of the clinic isolates of Edwardsiella tarda, an important pathogen infecting both of human and fish, are commonly found serum-resistant. To explore the potential mechanisms, we applied gas chromatography-mass spectrometry (GC-MS)-based metabolomics approaches to profile the metabolomes of E. tarda EIB202 in the presence or absence of serum stress. We found that tricarboxylic acid (TCA) cycle was greatly enhanced in the presence of serum. The quantitative real-time PCR (qRT-PCR) and enzyme activity assays validated this result. Furthermore, exogenous succinate that promotes the TCA cycle increased serum resistance, while TCA cycle inhibitors (bromopyruvate and propanedioic acid) that inhibit TCA cycle, attenuated serum resistance. Moreover, the enhanced TCA cycle increased membrane potential, thus decreased the formation of membrane attack complex at cell surface, resulting serum resistance. These evidences suggested a previously unknown membrane potential-dependent mechanism of serum resistance. Therefore, our findings reveal that pathogen mounts a metabolic trick to cope with the serum complement-mediated killing.