sRNA-051调控高毒力肺炎克雷伯菌耐药及毒力变化的机制研究

碳青霉烯类耐药高毒力肺炎克雷伯菌（CR-hvKP）在全球范围内产生和流行，具有强毒力、多重耐药、易感染成重症等特点，严重危害人类健康。sRNA（small regulatory RNA）是细菌的调节因子，参与感应环境和生理调节等重要过程。但sRNA在CR-hvKP菌株耐药及毒力中的作用尚未见报道。前期采用高通量测序及qRT-PCR验证发现sRNA-051在亚胺培南诱导产生CR-hvKP中表达上调，缺失sRNA-051可降低其抗药性及毒力。因此，我们假设sRNA-051通过影响CR-hvKP菌特定靶标mRNA表达及功能，进而调控其抗药性和毒力。本项目拟构建sRNA-051缺陷及过表达菌，结合小鼠脓毒症模型，探讨其对CR-hvKP耐药及毒力的调控作用，并通过生物信息学预测联合比较蛋白组学，鉴定与sRNA-051相互作用的靶标mRNA，探讨其调控分子机制，为控制CR-hvKP播散提供新途径。

Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) isolates have emerged and are being reported worldwide, which often display multi-drug resistance,relatively high level of virulence and big trend to develop severe sepsis and posed a serious health threat to human beings. Bacterial sRNAs (small regulatory RNAs) can act as regulators to participate in various physiological activities and environmental perception. However, there is no report on the roles of sRNA in the resistance and virulence of CR-hvKP. Our previous study showed that the sRNA-051 expression in the CR-hvKP induced by imipenem was increased, and it’s absence could reduce the resistance and virulence of CR-hvKP. Thus we hypothesize that the sRNA-051 may regulate the resistance and virulence of CR-hvKP through the interaction with special mRNA. This study will explore the regulation effect on the resistance and virulence of CR-hvKP by using the sRNA-051 gene-deletion and over-expression mutants of CR-hvKP and a mouse model of sepsis, and identify the special mRNA interacting with sRNA-051 by bioinformatics prediction and comparative proteomics analysis. This study will provide a new way to control the resistance and virulence of CR-hvKP through clarifying the mechanism of regulations of sRNA-051.