State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
College of Life Science and Technology, Huazhong Agriculture University, Wuhan, China.
Front Immunol. 2018 May 16;9:1063. doi: 10.3389/fimmu.2018.01063. eCollection 2018.
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 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 complement evasion. The C3 deposition and membrane attack complex (MAC) formation on the surface of -deleted mutant strain Δ are demonstrated to be significantly higher than the parental strain SC-19 and the complementary strain CΔ. The abilities of anti-phagocytosis, survival in blood, and colonization of Δ are obviously reduced. SntA can interact with C1q and inhibit hemolytic activity 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.
是一种新兴的人畜共患病病原体，可导致类似链球菌中毒性休克的综合征（STSLS）、脑膜炎、败血症，甚至在人和猪中突然死亡。严重的败血症表明，这种细菌可以逃避宿主补体的监测。在我们之前的研究中，已经鉴定出一种功能未知的蛋白 SntA 是一种血红素结合蛋白，有助于猪的毒力。SntA 可以与宿主抗氧化蛋白 AOP2 相互作用，从而抑制其抗氧化活性。在本研究中，SntA 被鉴定为一种细胞壁锚定蛋白，是逃避宿主补体的重要参与者。已经证明，-缺失突变株 Δ 表面的 C3 沉积和膜攻击复合物（MAC）的形成明显高于亲本株 SC-19 和互补株 CΔ。Δ 的抗吞噬、血中存活和定植能力明显降低。SntA 可以与 C1q 相互作用并抑制经典途径的溶血活性。补体激活测定表明，SntA 还可以直接激活经典途径和凝集素途径，导致补体消耗。这两种逃避补体的策略可能对这种人畜共患病病原体的发病机制至关重要。鉴于 SntA 在许多革兰氏阳性菌中是一种具有双功能的 2',3'-环核苷酸 2'-磷酸二酯酶/3'-核苷酸酶，这些逃避补体的策略可能具有共同的生物学意义。
