Amentoflavone Ameliorates Streptococcus suis-Induced Infection In Vitro and In Vivo
Amentoflavone Ameliorates Streptococcus suis-Induced Infection In Vitro and In Vivo
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穗花果黄酮可改善猪链球菌引起的体外和体内感染
DOI：
10.1128/aem.01804-18
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发表时间：
2018-12-01
影响因子：
4.4
通讯作者：
Wang, Jianfeng
中科院分区：
文献类型：
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作者：
Shen, Xue;Niu, Xiaodi;Wang, Jianfeng
猪链球菌是一种重要的人畜共患病病原体，在世界范围内给养猪业造成了巨大的经济损失和严重的公共卫生问题。迫切需要开发一种新的有效的防治策略来防治猪链球菌病。在这里，双黄酮酮，一种从中草药中分离出来的天然双黄酮类化合物，其抗S.Suis活性，被认为是一种有效的拮抗剂，不干扰猪溶血素(SLY)的表达。双黄酮有效地抑制了Sly齐聚，这是其成孔活性的关键。氨基黄酮可降低猪链球菌对巨噬细胞(J774细胞)的细胞毒作用。此外，接受氨基黄酮组感染猪链球菌的小鼠显示出较低的死亡率和细菌负荷。此外，在猪链球菌感染的细胞模型中，氨基黄酮显著减少肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)和白介素6的产生。对信号通路的分析表明，氨基黄酮通过调节p38、Jun氨基末端蛋白激酶1和2(JNK1/2)以及核因子-kappa B通路，减轻了猪链球菌感染细胞的炎症反应。氨基黄酮类抗猪链球菌感染的毒力和抗炎作用为其在未来药物治疗猪链球菌病中的应用提供了可能性。抗生素在猪链球菌感染的治疗和预防中的广泛使用在养猪业引起了人们对耐药菌株的关注。使用抗毒力药物有潜在的好处，主要是因为减少了细菌耐药性发展的选择压力。在本研究中，我们发现氨基黄酮体内外均具有抗猪链球菌2型(SS2)感染的作用。结果表明，氨基黄酮类化合物具有较强的抗炎和毒力作用，且无抗菌活性，且副作用较少，是一种很有前途的抗感染药物。
Streptococcus suis, an important zoonotic pathogen, has caused considerable economic losses in the swine industry and severe public health issues worldwide. The development of a novel effective strategy for the prevention and therapy of S. suis is urgently needed. Here, amentoflavone, a natural biflavonoid compound isolated from Chinese herbs that has negligible anti-S. suis activity, was identified as a potent antagonist of suilysin (SLY)-mediated hemolysis without interfering with the expression of SLY. Amentoflavone effectively inhibited SLY oligomerization, which is critical for its pore-forming activity. The treatment with amentoflavone reduced S. suis-induced cytotoxicity in macrophages (J774 cells). Furthermore, S. suis-infected mice that received amentoflavone exhibited lower mortality and bacterial burden. Additionally, amentoflavone significantly decreased the production of tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 in an S. suis-infected cell model. Analyses of signaling pathways demonstrated that amentoflavone reduced S. suis-induced inflammation in S. suis serotype 2 (SS2)-infected cells by regulating the p38, Jun N-terminal protein kinase 1 and 2 (JNK1/2), and NF-kappa B pathways. The antivirulence and anti-inflammatory properties of amentoflavone against S. suis infection provide the possibility for future pharmaceutical application of amentoflavone in the treatment of S. suis infection.IMPORTANCE The widespread use of antibiotics in therapy and in the prevention of Streptococcus suis infection in the swine industry raises concerns for the emergence of a resistant strain. The use of antivirulence agents has potential benefits, mainly because of the reduced selective pressure for the development of bacterial resistance. In this study, we found that amentoflavone is an effective agent against S. suis serotype 2 (SS2) infection both in vitro and in vivo. Our results demonstrated that amentoflavone is a promising anti-infective therapeutic for S. suis infections, due to its antivirulence and anti-inflammatory effects without antibacterial activity, with fewer side effects than conventional antibacterial agents.