金黄色葡萄球菌SprC下调免疫逃避蛋白Efb表达的分子机制

我们前期发现金黄色葡萄球菌SprC（致病岛小RNA C）能结合efb mRNA下调Efb表达，但两者结合的核苷酸及影响此结合和结合后mRNA稳定性的因素未明。Efb是金黄色葡萄球菌重要毒力因子，能抑制宿主天然免疫应答。据研究：细菌sRNA主要通过结合mRNA核糖体结合位点（RBS）影响靶蛋白翻译，RNA伴侣Hfq能促进两者结合，结合后可能触发RNase III活性影响mRNA稳定性。故推测SprC下调Efb表达可能是通过结合efb mRNA RBS实现的；Hfq和RNase III可能促进两者结合及降低mRNA稳定性。本项目拟以分子生物学、生物信息学及生物化学等方法阐明SprC下调Efb表达的分子机制，探讨Hfq在SprC与efb mRNA结合中的作用及RNase III对efb mRNA 稳定性的影响。研究结果有助于深入了解金黄色葡萄球菌致病机理，为改进该菌感染的预防和治疗策略提供线索。

In the previous experiments, we found SprC (small pathogenicity island RNA C) down-regulated the Efb expression by binding to efb mRNA in Staphylococcus aureus (S. aureus). However, the nucleotides interacting between SprC and efb mRNA and the factors affecting the combination of the both RNA and the stability of mRNA after the binding are not to be elucidated. Efb is the significant virulence factor of S. aureus. It can inhibit the host innate immune responses. The previous studies have shown most of bacterial sRNAs regulate the proteins expression in translation level by the binding to the ribosome-binding site (RBS) of the target mRNA. The RNA chaperone Hfq can promote the duplex formation between sRNA and target mRNA. This binding may trigger the hydrolysis activity of RNase III affecting the stability of target mRNA. Therefore, we speculate the mechanism of SprC down-regulating the expression of Efb can be the antisense binding to the RBS of efb mRNA. Hfq and RNase III can produce a marked effect in promoting the binding of SprC to efb mRNA and reducing the stability of efb mRNA, respectively. In this investigation we will elucidate the molecular mechanism of SprC down-regulating Efb expression, and explore the roles of Hfq in promoting the SprC-efb mRNA duplex formation and RNase III in affecting the stability of efb mRNA by the methods of molecular biology, bioinformatics and biochemistry. This study will help us deeply understand the pathogenesis of S. aureus, and give a clue for improving the prevention and therapy strategies of S. aureus infections.