非编码RNA(sRNA)对阪崎克罗诺杆菌致病性的影响及分子机理

阪崎克罗诺杆菌是一种重要食源性致病菌，造成了80%以上导致新生儿死亡的致病菌感染，其致病过程包括侵染肠上皮细胞、在血液中生存、穿越血脑屏障等多个环节。sRNA已被证明在多种肠道致病菌的致病过程中发挥重要作用，但sRNA在阪崎克罗诺杆菌致病性中的作用和相关机制尚缺乏研究。本项目针对前期研究中发现的、可影响阪崎克罗诺杆菌不同阶段致病能力的5种sRNA，利用高通量组学技术及分子生物学、生物化学、动物实验等手段，对其作用和分子机制进行系统研究，包括：确定sRNA的下游作用靶点及调节方式，分析其影响致病性的调控通路；鉴定sRNA的上游调控因子及响应的宿主体内环境信号，揭示sRNA介导的阪崎克罗诺杆菌与宿主相互作用机制等。研究成果将使我们深入认识sRNA与阪崎克罗诺杆菌致病性之间的关系，对理解该菌的致病机理和进化机制具有重要意义，并可为相关预防和治疗方法的探索提供新靶点。

Cronobacter sakazakii is an important foodborne pathogen, which is reported to be responsible for up to 80% of infant deaths associated with infection. The key steps in the pathogenicity process of C. sakazakii include: adherence to and invasion of the intestinal epithelial cells, survival in the blood, and traversal of the blood-brain barrier. Non-coding small RNA (sRNA) have been reported to be associated with the virulence of many enteropathogenic bacteria. However, the role of sRNA in the pathogenicity of C. sakazakii still remains unknown. We have identified 5 sRNAs which were involved in the different steps in the pathogenicity process of C. sakazakii. In this project, we will systematically analyze the molecular mechanisms by which these sRNAs influence C. sakazakii virulence, using high-throughput omics methods, molecular biological methods, biochemical methods and animal experiments. We will identify and determine the target genes of these sRNAs, and reveal the downstream regulatory pathways by which these sRNAs influence the bacterial pathogenicity. Furthermore, we will investigate which and how upstream regulators and environmental signals regulate the expression of these sRNAs. This will contribute to understanding the interaction between hosts and C. sakazakii mediated by sRNAs. The outcome of this project will largely enhance our understanding for the relationship between sRNAs and pathogenicity of C. sakazakii, and provide novel insights for the evolution of this important pathogen. The results will also provide novel ideas and targets to prevent and control C. sakazakii infection.