猪链球菌（S. suis）是一种重要的人畜共患病病原,同时也是一种携带有前噬菌体的重要病原菌。申请者前期研究发现猪链球菌2型菌株SS2-4整合噬菌体SMP基因组后毒力增强，但其机制尚不清楚。本项目拟通过对噬菌体SMP裂解性状态和溶原性状态基因表达差异的分析，对差异表达基因进行蛋白表达、纯化及毒力分析；利用溶原菌株SS2-4（SMP）为载体对噬菌体的差异表达基因进行缺失，用斑马鱼模型及HEp-2细胞评价缺失株的毒力；通过斑马鱼全基因组表达谱芯片测序，进行宿主差异表达基因分析、GO富集显著性分析、KEGG pathway富集显著性分析及蛋白网络构建分析，阐明噬菌体的差异表达基因对宿主基因表达的影响；通过溶原株SS2-4（SMP）和缺失株的转录组，分析噬菌体的差异表达基因对宿主菌SS2-4基因表达的影响。本研究旨在阐明噬菌体增强宿主菌毒力的机制，为猪链球菌噬菌体与宿主菌毒力关系的研究提供参考。

Streptococcus suis (S.suis) is an important zoonosis, as well as an important pathogen that can carry prophages. According to our previous research, S. suis serotype 2 isolate SS2-4 became more virulent after be integrated with the phage SMP. However, the mechanism of the virulence increasing is unknown yet. Thus, this study attempt to find out the key genes of the phage SMP, which express at different levels between the lytic and lysogenic life circles. The key genes will be cloned, expressed, and purified, and the virulence of the purified protein will be studied. The SS2-4(SMP) mutants will be constructed by deleting the genes mentioned above. Zebrafish and HEp-2 cell lines will be used to evaluate the virulence of the mutant; gene expression microarray of infected zebrafish will be used to evaluate the role of the deleted genes playing in the virulence of host strain , by the variance analysis of host genes expression, GO enrichment , KEGG pathway enrichment , and protein network build; transcriptome sequencing of the wild SS2-4(SMP) and the SS2-4(SMP) mutant will be studied to evaluate the effect of deleted genes on the host genes expression. This research will illuminate the mechanism of phage increasing the virulence of the host strain and contribute to the research on the role of S.suis phage playing in its host virulence.