The Surface-Exposed Protein SntA Contributes to Complement Evasion in Zoonotic Streptococcus suis.
The Surface-Exposed Protein SntA Contributes to Complement Evasion in Zoonotic Streptococcus suis.
复制标题
表面暴露蛋白 SntA 有助于人畜共患猪链球菌的补体逃避
DOI：
10.3389/fimmu.2018.01063
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发表时间：
2018
影响因子：
7.3
通讯作者：
Zhou R
中科院分区：
文献类型：
--
作者：
Deng S;Xu T;Fang Q;Yu L;Zhu J;Chen L;Liu J;Zhou R
猪链球菌（Streptococcus suis）是一种新型的人畜共患病原体，可引起人和猪的链球菌中毒性休克样综合征（STSLS）、脑膜炎、败血症，甚至猝死。严重的败血症表明该细菌可以逃避宿主补体监测。在我们以前的研究中，一个功能未知的S.猪的胰岛素已被鉴定为血红素结合蛋白，并对猪的毒性有贡献。SntA可以与宿主抗氧化蛋白AOP 2相互作用，从而抑制其抗氧化活性。在本研究中，SntA被鉴定为细胞壁锚定蛋白，在S.猪补体逃避。结果表明，缺失突变株ΔsntA的C3沉积量和膜攻击复合物（MAC）的形成量显著高于亲本株SC-19和互补株CΔsntA。ΔsntA的抗吞噬能力、血中存活能力和体内定殖能力明显降低。SntA可以通过经典途径与C1 q相互作用并抑制溶血活性。补体激活试验表明，SntA也可以直接激活经典和凝集素途径，导致补体消耗。这两种补体逃避策略可能对这种人畜共患病病原体的发病机制至关重要。考虑到SntA是一种双功能的2′，3 ′-环核苷酸2′-磷酸二酯酶/3′-核苷酸酶，在许多种革兰氏阳性菌中，这些补体逃避策略可能具有共同的生物学意义。
Streptococcus suis is an emerging zoonotic pathogen causing streptococcal toxic shock like syndrome (STSLS), meningitis, septicemia, and even sudden death in human and pigs. Serious septicemia indicates this bacterium can evade the host complement surveillance. In our previous study, a functionally unknown protein SntA of S. suis has been identified as a heme-binding protein, and contributes to virulence in pigs. SntA can interact with the host antioxidant protein AOP2 and consequently inhibit its antioxidant activity. In the present study, SntA is identified as a cell wall anchored protein that functions as an important player in S. suis complement evasion. The C3 deposition and membrane attack complex (MAC) formation on the surface of sntA-deleted mutant strain ΔsntA are demonstrated to be significantly higher than the parental strain SC-19 and the complementary strain CΔsntA. The abilities of anti-phagocytosis, survival in blood, and in vivo colonization of ΔsntA are obviously reduced. SntA can interact with C1q and inhibit hemolytic activity via the classical pathway. Complement activation assays reveal that SntA can also directly activate classical and lectin pathways, resulting in complement consumption. These two complement evasion strategies may be crucial for the pathogenesis of this zoonotic pathogen. Concerning that SntA is a bifunctional 2′,3′-cyclic nucleotide 2′-phosphodiesterase/3′-nucleotidase in many species of Gram-positive bacteria, these complement evasion strategies may have common biological significance.