金黄色葡萄球菌群体感应信号分子AI-2的受体鉴定及调控致病性的分子机制

群体感应是细菌通过个体间通讯实现密度依赖性种群行为的调控机制。酰基高丝氨酸内酯及寡肽作为信号分子介导的群体感应被广泛研究，且AI-2群体感应在革兰氏阴性细菌中的功能也较为清楚。我们发现金黄色葡萄球菌AI-2信号分子能够调控致病性，但是通过何种受体及具体的调控机制尚不清楚。敲除AI-2合成酶基因luxS可导致转录因子SaaR编码基因表达水平提高，而分别敲除luxS与saaR后，致病性基因的表达变化呈现相关性。冷冻电镜实验初步证明，SaaR可以与AI-2分子产生特异性结合效应。这些结果显示AI-2信号分子可能通过结合SaaR使其发生构象变化，来行使AI-2/SaaR的群体感应调控功能，由此调控相关靶基因的转录水平和群体行为。本项目期望揭示金黄色葡萄球菌AI-2/SaaR群体感应调控致病性的分子机制 ，为革兰氏阳性细菌病原体感染治疗提供新型药物靶点和策略。

Quorum sensing is a bacterial cell-cell communication mechanism in which individuals coordinate their population behavior in a density-dependent manner. It has been widely recognized that AHLs and oligopeptides can act as quorum sensing signals, and autoinducer 2 (AI-2)-mediated quorum sensing has been functionally and mechanically revealed. Our previous data indicated that AI-2 can regulate virulence by serving as a signaling molecule in Staphylococcus aureus, but the AI-2 receptor and regulatory mechanism remain mysterious. Genetic deletion of luxS encoding AI-2 synthase led to a higher transcription level of saaR encoding a transcriptional factor. The phenotypes of virulence were coordinated when luxS or saaR was deleted respectively. Cryoelectron microscopy analysis suggests that SaaR can specifically bind to AI-2. These results imply that binding between AI-2 and SaaR can change the conformation of the transcriptional factor, by which AI-2/SaaR perform quorum sensing regulation and coordinate population behavior. This study aims to elucidate the molecular mechanisms of virulence modulated by AI-2/SaaR quorum sensing. This research will not only deepen our understanding of the function and regulatory mechanisms of quorum sensing in Staphylococcus aureus, but also provide novel targets and strategies for the treatment of infection caused by Gram-positive bacterial pathogens.