副血链球菌调控因子FimR调控网络构建及其在氧化应激中的作用

项目名称： 副血链球菌调控因子FimR调控网络构建及其在氧化应激中的作用

项目编号： No.31200928

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 耿佳宁

作者单位： 中国科学院北京基因组研究所

项目金额： 22万元

中文摘要： 副血链球菌在牙菌斑和瓣膜心内膜炎发生过程中发挥着重要作用，但是对副血链球菌毒力基因的研究局限在对fap1基因簇和fimCBA-tpx 操纵子上。而调控因子如何调控毒力基因的表达，还没有报道。序列同源比对表明FimR蛋白是调控蛋白DtxR家族蛋白成员之一，这类蛋白家族在细菌中参与调控生物体内抗氧化体系蛋白表达，从而在心内膜炎发生中发挥着重要作用。前期研究表明FimR除了调控fimCBA-tpx操纵子之外，还可以结合其它一些基因，是全局调控因子，参与抗氧化应激反应。本项目利用ChIP-seq技术和RNA-seq技术相结合，鉴定直接结合基因和次级调控基因，从全基因组水平建立比较完善的FimR调控网络；利用基因突变技术，从分子水平揭示FimR如何调控毒力基因fimA和其它一些靶基因，在抗氧化应激反应中发挥作用，找到可能与心内膜炎发生有关的靶基因，为疾病的治疗提供理论基础。

中文关键词： 副血链球菌；firmR基因；RNA-seq；差异表达；调控网络

英文摘要： Streptococcus parasanguinis FW213 (S. parasanguinis) is a member of the viridans streptococci that constitute the major population of the oral microbial ecosystem. In its primary niche, oral cavity, S. parasanguinis is one of the early colonizers of the tooth surface. S. parasanguinis and other viridans streptococci can colonize heart valves and are common causes of native and prosthetic heart valves endocarditis. The infection is often persistent and difficult to treat, and can result in considerable morbidity and mortality despite modern antimicrobial and surgical treatment. Despite the significance of S. parasanguinis in the oral ecosystem and systemic infection, studies on its pathogenic factors have been limited to the fimCBA-tpx operon and the fap1 gene cluster in the past. Although the cellular location of FimA determined by anti-FimA serum is at the tips of the long fimbriae of FW213, very little is known how FimR regulates the expression of fimCBA-tpx operon and other unknown virulence genes and subsequent development of endocarditis. FimR, a homologue of the iron-regulated DtxR-like protein, regulates a spectrum of genes involved in oxidative stress defense and development of endocarditis. Our preliminary results of electrophoretic mobility shift assay (EMSA) and paraquat killing experiment indicated

英文关键词： Streptococcus parasanguinis FW213；firmR；RNA-seq；differential expression；regulatory network