The Effect of the Potential PhoQ Histidine Kinase Inhibitors on Shigella flexneri Virulence

doi:10.1371/journal.pone.0023100

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物发现与设计中心

	The Effect of the Potential PhoQ Histidine Kinase Inhibitors on Shigella flexneri Virulence
	Cai, Xia 2,3,4; Zhang, Jian 5; Chen, Mingliang 1; Wu, Yang 2,3,4; Wang, Xueqing 2,3,4; Chen, Jiayu 2,3,4; Zhang, Junqin 2,3,4; Shen, Xu5 ; Qu, Di 2,3,4; Jiang, Hualiang5
刊名	PLOS ONE
	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).