产超广谱β-内酰胺酶（Extended Spectrum β-Lactamase，ESBL）肺炎克雷伯杆菌是引起呼吸道感染常见致病菌之一，CTX-M酶是全球最流行的ESBL。目前研究发现，blaCTX-M基因启动子高度保守，但blaCTX-M表达具有差异性，机制不清。我们的预实验提示，启动子与blaCTX-M基因的间隔序列不同，blaCTX-M启动子活性也有差异。因此提出假说：保守启动子和blaCTX-M编码序列的间隔序列可能是CTX-M表达调控的关键元件。为验证这一假说，我们利用以绿色荧光蛋白为报告基因的质粒为载体，构建包含保守启动子和不同间隔序列的重组质粒，通过检测启动子活性和转录组测序，寻找对blaCTX-M基因表达起决定作用的关键环节，探讨blaCTX-M差异表达的可能机制。本研究将对临床控制产CTX-M KP菌株的传播和感染具有重要意义，并为寻找新的抗菌药物靶点提供策略和思路。

The extended spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (KP) is one of major respiratory tract infective pathogens and CTX-M enzyme is the most popular ESBL throughout the world. The present studies show that the expression of blaCTX-M is heterogeneous which is regulated by a highly conserved promoter. And the molecular mechanism has not been completely understood yet. Our preliminary study has found that the difference of promoters activity are associate with the change of spacer sequences between the promoter and the blaCTX-M coding sequence. Therefore, we propose a hypothesis: the spacer sequences between the highly conserved promoter and the blaCTX-M coding sequence may play a key role in of blaCTX-M expression. In order to verify the hypothesis, we use green fluorescent protein as a reporter gene plasmid vector to recombine plasmid containing the conserved promoter sequences and different spacer sequences. By detecting the promoter activity and RNA-seq, we look for the key point in blaCTX-M gene expression and explore the possible mechanism of heterogeneous blaCTX-M gene expression. This research can play an important role in controlling the dissemination and infection of CTX-M-producing KP and provide innovative strategies and ideas for exploration in new antimicrobial drug target spots.