Morin Attenuates Streptococcus suis Pathogenicity in Mice by Neutralizing Suilysin Activity.
Morin Attenuates Streptococcus suis Pathogenicity in Mice by Neutralizing Suilysin Activity.
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DOI：
10.3389/fmicb.2017.00460
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发表时间：
2017
影响因子：
5.2
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Li G;Lu G;Qi Z;Li H;Wang L;Wang Y;Liu B;Niu X;Deng X;Wang J
猪链球菌是一种革兰氏阳性病原体，被广泛认为是猪感染的重要病原体，它也被认为是引起多种人畜共患病，如脑膜炎、多发性关节炎和肺炎。溶血素（SLY）是一种细胞外成孔毒素，属于胆固醇依赖性细胞溶血素家族，是猪链球菌2型荚膜（SS2）的重要毒力因子。本研究发现，缺乏抗SS2活性的天然类黄酮桑苷水合物（morin hydrate, morin）可抑制SLY的溶血活性，保护J774细胞免受SS2诱导的损伤，并保护小鼠免受SS2感染。此外，通过分子建模和突变分析，我们发现morin与SLY的“茎”结构域2结合，阻碍其从单体形式转化为低聚物形式，从而导致SLY活性丧失。我们的研究表明，morin通过一种中断七聚体形成的新机制阻碍了SLY的细胞裂解活性。这些发现可能会导致开发有希望的治疗SS2感染的候选药物。
Streptococcus suis, a Gram-positive pathogen, is widely recognized as an important agent of swine infection, and it is also known to cause a variety of zoonoses, such as meningitis, polyarthritis and pneumonia. Suilysin (SLY), an extracellular pore-forming toxin that belongs to the cholesterol-dependent cytolysin family, is an essential virulence factor of S. suis capsular type 2 (SS2). Here, we found that morin hydrate (morin), a natural flavonoid that lacks anti-SS2 activity, inhibits the hemolytic activity of SLY, protects J774 cells from SS2-induced injury and protects mice from SS2 infection. Further, by molecular modeling and mutational analysis, we found that morin binds to the “stem” domain 2 in SLY and hinders its transformation from the monomer form to the oligomer form, which causes the loss of SLY activity. Our study demonstrates that morin hinders the cell lysis activity of SLY through a novel mechanism of interrupting the heptamer formation. These findings may lead to the development of promising therapeutic candidates for the treatment of SS2 infections.