一种新型信号短肽调控噬菌体裂解溶原决定的信号通路研究

噬菌体是地球上丰度最高的生物体。40~50%的细菌基因组上携带噬菌体DNA，以溶原菌的形式存在。噬菌体裂解溶原转换可以改变宿主细菌的表型和生理特性，其生命周期的调控是噬菌体研究领域的前沿热点。近期，在噬菌体中鉴定出一种新型的溶原决定调控方式。噬菌体在感染枯草芽胞杆菌后，产生信号短肽，与胞内受体蛋白AimR结合，并激活下游基因表达，促进溶原的发生。在前期工作中，我们揭示了AimR蛋白对信号短肽和DNA的特异识别模式。本项目在其工作基础上，详细研究裂解溶原决定的信号通路。我们将通过转录组分析筛选信号短肽调控噬菌体溶原决定的关键基因；利用基因敲除和过表达等方法来验证关键基因的生物学功能；通过质谱鉴定其相互作用蛋白，结合蛋白质结构分析关键蛋白的功能，确定信号短肽调控噬菌体溶原决定的信号通路。本研究的完成，对深入理解噬菌体间的信号交流现象有理论意义，为微生物发酵工业中噬菌体污染提供新思路。

Bacteriophages are the most abundant organisms on earth. Genetically, temperate phages have been identified in ~40–50% of microbial genomes. Temperate phages can switch between infection modes that have significant affects on the phenotype and physiological characteristics of host bacteria. A recent study that examined the lysogeny dynamics of the Bacillus phage found that small-molecule communication between phages is used to coordinate the lysogeny decision. After infection with Bacillus subtilis, the bacteriophage produces a short signal peptide, which binds to the intracellular receptor protein AimR, activates downstream gene expression, and promotes the occurrence of lysogeny. In the previous work, we have elucidated the recognition pattern of AimR protein for signal short peptides and target DNA. On the basis of its work, this project uses transcriptome analysis to screen key genes involve in phage lysis-lysogeny decisions; phage gene knockout mutants and overexpression assays are used to verify the biological functions of key genes; and their interaction proteins are identified by mass spectrometry. Protein structure analysis will also contribute to determine the phage lysogenic transition pathways. This project will provides new insights into the mechanism of communication-based lysogeny decisions. Understanding lytic-lysogenic dynamics may aid in improving biotechnological processes, such as control phage contamination in fermentation industry.