插入子ISEcp1及其相邻间隔序列介导产CTX-M型志贺菌耐药机制研究

志贺菌是引起痢疾的重要医学病原菌，近年来其对头孢类抗生素的高水平耐药增加了痢疾的治疗难度。CTX-M型酶是在志贺菌等肠道致病菌中引起头孢菌素耐药且流行最为广泛的超广谱β-内酰胺酶之一。前期研究表明，blaCTX-M上游的插入序列ISEcp1能够增强志贺菌blaCTX-M的表达，而且在ISEcp1与不同blaCTX-M亚型之间存在的不同类型Spacers间隔序列也很可能在耐药性的表达中发挥了重要作用。本研究首次针对志贺菌中插入子ISEcp1和不同类型Spacers介导产CTX-M型志贺菌对头孢类抗生素的耐药机制进行深入研究，掌握各结构对志贺菌耐药性产生以及强弱作用规律，探究ISEcp1、Spacers的序列结构、长度和蛋白识别位点等因素对志贺菌耐药性的影响，研究结果不仅能帮助我们更全面地了解耐头孢菌素志贺菌的耐药特性与耐药机制，也为寻求解决志贺菌耐药性的新方法和新策略提供科学依据和理论支撑。

Shigella is an important medical pathogen causing dysentery. In recent years, its high level of resistance to cephalosporins has increased the difficulty in the treatment of dysentery. The CTX-M enzyme is one of the most popular extended spectrum β - lactamases that cause cephalosporin resistance in Shigella and other intestinal pathogens. Previous studies have shown that the insertion sequence ISEcp1 upstream of blaCTX-M can enhance the expression of blaCTX-M in Shigella, and there are different types of spacer sequences between ISEcp1 and different subtypes of blaCTX-M. These spacers may also play an important role in antibiotic resistance. In this study, we focused on the mechanism of cephalosporins resistance of CTX-M producing Shigella mediated by different types of spacers, ISEcp1 and blaCTX-M, exploring the rules of each structure on the generation and strength of antibiotic resistance. We also aim to study the effect of sequence structure, length and protein recognition sites of ISEcp1 and spacers on the resistance of CTX-M producing Shigella. The results can not only help us understand the antibiotic resistance characteristics and mechanism of cephalosporin resistant Shigella more comprehensively, but also provide scientific basis and theoretical support for seeking new methods and strategies to solve the antibiotic resistance of Shigella.