The effect of the potential PhoQ histidine kinase inhibitors on Shigella flexneri virulence.
The effect of the potential PhoQ histidine kinase inhibitors on Shigella flexneri virulence.
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潜在的 PhoQ 组氨酸激酶抑制剂对福氏志贺氏菌毒力的影响
DOI：
10.1371/journal.pone.0023100
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Jiang H
中科院分区：
文献类型：
--
作者：
Cai X;Zhang J;Chen M;Wu Y;Wang X;Chen J;Zhang J;Shen X;Qu D;Jiang H
PhoQ/PhoP是志贺菌毒力调控的重要双组分系统。我们探讨了PhoQ/PhoP系统是否是一个有希望的新抗生素靶点。弗氏菌感染通过高通量筛选和酶活性偶联分析，发现四个化合物为潜在的PhoQ抑制剂。这些化合物不仅抑制SF-PhoQc自磷酸化的活性，而且在表面等离子体共振响应中显示出与SF-PhoQc蛋白的高结合亲和力。色葡萄福氏细胞侵袭实验表明，其中三种潜在的PhoQ抑制剂抑制了S. flexneri 9380.在小鼠Sereny试验中，接种S.用潜在的PhoQ抑制剂1、2、3或4预处理的弗氏9380没有显示出炎症，而用S.单独的Flexneri 9380显示严重的角膜结膜炎症。所有四种潜在的PhoQ抑制剂均未显示出显著的细胞毒性或溶血活性。这些数据表明，四种潜在的PhoQ抑制剂抑制了S. PhoQ/PhoP是一个很有前途的靶点，可用于开发抗福氏志贺菌的药物。弗氏菌感染
PhoQ/PhoP is an important two-component system that regulates Shigella virulence. We explored whether the PhoQ/PhoP system is a promising target for new antibiotics against S. flexneri infection. By using a high-throughput screen and enzymatic activity coupled assay, four compounds were found as potential PhoQ inhibitors. These compounds not only inhibited the activity of SF-PhoQc autophosphorylation but also displayed high binding affinities to the SF-PhoQc protein in the Surface Plasmon Resonance response. A S. flexneri cell invasion assay showed that three of these potential PhoQ inhibitors inhibit the invasion of HeLa cells by S. flexneri 9380. In a Mouse Sereny test, mice inoculated with S. flexneri 9380 pre-treated with the potential PhoQ inhibitors 1, 2, 3 or 4 displayed no inflammation, whereas mice inoculated with S. flexneri 9380 alone displayed severe keratoconjunctival inflammation. All four potential PhoQ inhibitors showed no significant cytotoxicity or hemolytic activity. These data suggest that the four potential PhoQ inhibitors inhibited the virulence of S. flexneri and that PhoQ/PhoP is a promising target for the development of drugs against S. flexneri infection.
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影响因子：
56.9
作者：
Ernst, RK;Yi, EC;Miller, SI
通讯作者：
Miller, SI
影响因子：
56.9
作者：
Guo, L;Lim, KB;Miller, SI
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Miller, SI
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3
作者：
Giacometti, A;Cirioni, O;Scalise, G
通讯作者：
Scalise, G
影响因子：
56.9
作者：
Hung, DT;Shakhnovich, EA;Mekalanos, JJ
通讯作者：
Mekalanos, JJ
影响因子：
3.6
作者：
Kim, SK;WilmesRiesenberg, MR;Wanner, BL
通讯作者：
Wanner, BL