VicRK是少数低G+C值革兰氏阳性菌中高度保守的关键性双组分信号转导系统。该系统因具有调控细胞壁代谢和毒力等重要功能而成为现代病原菌防治中的有效靶标。无乳链球菌是近些年来引起我国南方罗非鱼大量死亡的主要病原，海南作为罗非鱼的主产区而损失严重。因此，在当前该菌致病机理不明，存在强耐药性问题和缺乏有效疫苗的情况下,利用VicRK可为该病原防治带来新的希望。目前,尚未发现有关无乳链球菌VicRK的功能研究。本课题拟采用生物信息学、蛋白质－DNA互作、数字基因表达谱分析等现代研究方法揭示VicRK系统在无乳链球菌基因组上的结合位点及其对下游调控基因的表达调节，并通过对这些调控基因的功能诠释，以及突变菌株的表型分析，阐述VicRK在无乳链球菌细胞壁代谢和在致病过程中的双重调控功能，评价其在无乳链球菌弱毒疫苗株开发和新型抗生素筛选中的可利用价值,为高危难防的鱼类无乳链球菌病害防治探索新的方向。

Both the nature of the regulon and the physiological role of the two component signal transdution system VicRK have remained uncharacterized in Streptococcus agalatiae. VicRK is highly conserved in and specific to the low-G+C content gram-positive bacteria.Because it is essential for viability in most of these bacteria by controlling cell wall metabolism and virulence factor expression, VicRK has been suggested as a prime antimicrobial target. In recent years, Streptococcus agalatiae has been recognized as one of the most serious bacterial diseases in tilapia culture and usually causes high mortality and lasts a long period of time.Hainan, as the main area of tilapia culture in China, has caused heavy losses. So, the VicRK is a new hope for the control of this dangerous disease. In this study, Bioinformatic assay and chromatin immunoprecipitation-sequencing (ChIP-Seq) assay will be performed to characterize the recognizing binding sequences and binding sites of VicR in the whole genome, and then the candidate genes which are directly regulated by VicR near binding regions will be predicted by detailed DNA motif analysis and confirmed by Gel mobility shift (GMSA）. Digital gene expression profiling RNA-Seq(quantification) [DGE RNA-Seq(quantification) ] assay will be applied to survey and figure out the expression direction of above modulated genes by VicR, and proved by RT-qPCR. Then, the VicRK regulation mechanism of murein biosynthesis and virulence factor expression will be predicted by combining all the above data and gene Go analysis. Last, the considerable potential as new target for antibiotic and vaccine development will be evaluated and uncovered in Streptococcus agalatiae by phenotype analysis of vicRK mutants.This study will enhance our understanding of the VicRK funciton in Streptococcus agalatiae and help us to develop an effective, novel strategy to eliminate this important potential bacterial agent of tilapias.