Aeromonas hydrophila suppresses complement pathways via degradation of complement C3 in bony fish by metalloprotease
Aeromonas hydrophila suppresses complement pathways via degradation of complement C3 in bony fish by metalloprotease
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DOI：
10.1016/j.fsi.2019.09.057
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发表时间：
2019-11-01
影响因子：
4.7
通讯作者：
Zhang, Yong-An
中科院分区：
文献类型：
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作者：
Chen, Dan-Dan;Li, Ji-Hong;Zhang, Yong-An
草鱼气单胞菌（Aeromonasseriae）是引起草鱼高死亡率的病原菌。补体系统作为天然免疫的前线防御，在抵抗病原体的免疫应答中起着重要作用。然而，A.草鱼补体系统的抑制作用尚不清楚。在这项研究中，我们描述了一个额外的机制使用的A。GD18逃避补体系统而在草鱼血清中存活。首先，A.草鱼血清的杀菌活性不受草鱼血清的影响。其次，溶血活性测定表明，A. Alcoha明显抑制旁路途径，这依赖于阻止膜攻击复合物（MAC）的形成或使其功能丧失。进一步的研究表明，A.草鱼血清中的补体C3是草鱼补体三条途径的核心成分，而草鱼血清中的补体C3被草鱼A降解，导致草鱼补体三条途径的抑制，从而导致草鱼A的血清抗性。你好酶切分析表明，A. Escherichia能有效地切割纯化的C3以及草鱼血清中的C3。最后，蛋白酶抑制剂的研究和质谱分析确定了分泌的金属蛋白酶弹性蛋白酶（AhE），这是存在于大量的粗ECPases，作为中央分子负责C3裂解。与野生株GD18相比，AhE基因敲除的tahe菌株的抗血清能力显著降低。我们的研究结果表明，A.在硬骨鱼中，通过降解与分泌的金属蛋白酶有关的补体C3来抑制补体途径，从而逃避血清杀伤。
Aeromonas hydrophila is a pathogen that causes high mortality in the grass carp. The complement system, as a frontline defence of innate immunity, plays an important role in the immune response against pathogens. However, the immunity evasion mechanism of A. hydrophila against the complement system of grass carp remains unclear. In this study, we described an additional mechanism used by A. hydrophila GD18 to evade the complement system and survive in grass carp serum. First, A. hydrophila evaded the bactericidal activity of grass carp serum. Second, the haemolytic activity assays showed that A. hydrophila obviously suppressed the alternative pathway, which depended on preventing the formation or disabling the function of the membrane-attack complex (MAC). Further research indicated that A. hydrophila targeted complement C3, the central component of the three complement pathways, and degraded it in the grass carp serum, leading to the inhibition of the complement pathways, which resulted in the serum-resistance of A. hydrophila. Furthermore, cleavage analyses showed that extracellular proteases (ECPases) of A. hydrophila efficiently cleaved purified C3 as well as C3 in grass carp serum. Finally, protease inhibitor studies and mass spectrum analysis identified the secreted metalloprotease elastase (AhE), which was present in large amounts in crude ECPases, as the central molecule responsible for C3 cleavage. Compared to wild strain GD18, the AhE knockout, tahe was dramatically reduced in the ability of serum resistance. Our findings suggested that A. hydrophila escaped serum-killing by suppressing the complement pathways via the degradation of complement C3 in bony fish, which was related to secreted metalloproteases.