BOX元件调控水平转移的肺炎链球菌黏附蛋白A基因表达的机制和生物学效应研究

Streptococcus pneumoniae is the major pathogenic bacteria of Community-Acquired Pneumonia. The virulence evolution of bacterial is one of key challenges for prevention of Streptococcus pneumoniae. Horizontal gene transfer is an important way to obtain virulence genes. How to regulate the expression of horizontally transferred genes and what is the biological effects based on the regulation are still unknown. In our early study, we found that expression abundance of horizontal transferred psaA gene was related to different forms of BOX elements. And BOX elements contains the conserved sequence which could been bind by transcription factor. These indicate: BOX elements are involved in the expression regulation of transferred psaA gene and effect Streptococcus pneumoniae virulence evolution. Based on the previous studies，this project will plan to clarify the mechanism of BOX elements regulating psaA gene expression, and to explain the relationship between the sequence of BOX elements and transcription factors which we predicted in early study. First, the recombinant strains with different BOX element’s secondary structure of RNA will be intend to build, and then the effects of virulence, environmental adaptability and gene expression patterns followed by differential psaA gene expression will be assessed. Based these works, it has the potential to clarify the mechanism and the biological effects of differential expressions of psaA genes, and find out the new clues to prevent Streptococcus pneumoniae.

肺炎链球菌是社区获得性感染最主要的致病菌，细菌自身毒力的进化是目前肺炎链球菌防治面临的重大挑战。基因水平转移是肺炎链球菌获得毒力基因实现毒力进化的重要途径，但对转移后基因表达的调控和相应的生物学效应却知之甚少。课题组前期研究发现：肺炎链球菌中转移的psaA基因表达水平与临近的BOX元件组成形式密切相关，而BOX元件包含可和转录因子结合的保守序列。据此推测：BOX元件参与调控转移后psaA基因的表达，影响肺炎链球菌的毒力进化。本项目拟在前期研究基础上，体外实验验证BOX元件序列与预测的转录因子间的相互作用，构建不同RNA折叠二级结构的BOX元件基因修饰菌株，明确其调控psaA表达的机制；体内实验评估BOX元件调控psaA差异表达对细菌毒力和环境适应能力的影响及其上下游基因的响应模式。以期阐释肺炎链球菌调控转移后psaA基因表达的可能机制及其生物学效应，为探索肺炎链球菌感染防御新途径提供线索。