The Effect of the Potential PhoQ Histidine Kinase Inhibitors on Shigella flexneri Virulence | |
Cai, Xia2,3,4; Zhang, Jian5; Chen, Mingliang1; Wu, Yang2,3,4; Wang, Xueqing2,3,4; Chen, Jiayu2,3,4; Zhang, Junqin2,3,4; Shen, Xu5![]() ![]() | |
刊名 | PLOS ONE
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2011-08-10 | |
卷号 | 6期号:8 |
ISSN号 | 1932-6203 |
DOI | 10.1371/journal.pone.0023100 |
文献子类 | Article |
英文摘要 | 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. |
资助项目 | Ministry of Science and Technology of China[2009ZX09303-005] ; Ministry of Science and Technology of China[2008ZX10003-016] ; Ministry of Science and Technology of China[2010DFA32100] ; National Natural Science Foundation of China[30800036] ; National Natural Science Foundation of China[J0730860] ; Scientific Technology Development Foundation of Shanghai[10410700600] ; Scientific Technology Development Foundation of Shanghai[09DZ1908602] ; Scientific Technology Development Foundation of Shanghai[08JC1401600] ; Fudan University[09FQ43] |
WOS关键词 | 2-COMPONENT REGULATORY SYSTEM ; QUORUM-SENSING INHIBITORS ; BACTERIAL SENSOR KINASE ; ESCHERICHIA-COLI ; PSEUDOMONAS-AERUGINOSA ; SIGNAL-TRANSDUCTION ; ANTIMICROBIAL PEPTIDES ; SEROVAR TYPHIMURIUM ; ACETYL PHOSPHATE ; SMALL MOLECULES |
WOS研究方向 | Science & Technology - Other Topics |
语种 | 英语 |
出版者 | PUBLIC LIBRARY SCIENCE |
WOS记录号 | WOS:000295454200042 |
内容类型 | 期刊论文 |
源URL | [http://119.78.100.183/handle/2S10ELR8/278443] ![]() |
专题 | 药物发现与设计中心 |
通讯作者 | Cai, Xia |
作者单位 | 1.Shanghai Municipal Ctr Dis Control & Prevent, Shanghai, Peoples R China 2.Fudan Univ, Inst Med Microbiol, Minist Hlth, Key Lab Med Mol Virol, Shanghai 200433, Peoples R China; 3.Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China; 4.Fudan Univ, Inst Med Microbiol, Minist Educ, Key Lab Med Mol Virol, Shanghai 200433, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med,Grad Sch, Drug Discovery & Design Ctr,State Key Lab Drug Re, Shanghai, Peoples R China; |
推荐引用方式 GB/T 7714 | Cai, Xia,Zhang, Jian,Chen, Mingliang,et al. The Effect of the Potential PhoQ Histidine Kinase Inhibitors on Shigella flexneri Virulence[J]. PLOS ONE,2011,6(8). |
APA | Cai, Xia.,Zhang, Jian.,Chen, Mingliang.,Wu, Yang.,Wang, Xueqing.,...&Jiang, Hualiang.(2011).The Effect of the Potential PhoQ Histidine Kinase Inhibitors on Shigella flexneri Virulence.PLOS ONE,6(8). |
MLA | Cai, Xia,et al."The Effect of the Potential PhoQ Histidine Kinase Inhibitors on Shigella flexneri Virulence".PLOS ONE 6.8(2011). |
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