ST11是我国耐碳青霉烯肺炎克雷伯菌的主要流行克隆菌株，该菌在胃肠道的定植与随后的感染密切相关，然而影响该菌胃肠道定植的关键因子及机制尚不明确。申请人预实验研究发现，pilL基因编码IV型菌毛，极有可能是ST11在胃肠道定植的关键基因。因此，本研究拟利用肺炎克雷伯菌ST11菌株构建pilL基因敲除株，通过对比野生株和敲除株在细菌运动活性、生物膜形成等方面的差异，分析pilL基因在肺炎克雷伯菌ST11中的生物学作用；通过细胞粘附侵袭实验和小鼠定植实验，验证pilL基因对肺炎克雷伯菌ST11在小鼠胃肠道定植能力的影响。在此基础上，通过进一步观察细菌定植部位小鼠胃肠道粘膜的病理组织变化、检测炎症因子转录和表达水平等方法，探讨pilL基因在肺炎克雷伯菌ST11胃肠道定植的关键机制。本研究的实施可为耐碳青霉烯肺炎克雷伯菌的防控提供理论基础与新思路。

ST11 is a major epidemic clone of carbapenem-resistant Klebsiella pneumoniae in our country. The colonization of this bacteria in gastrointestinal tract is closely associted with subsequent infection. However, the key factor controbuting the colonization in the gastrointestinal tract and the mechanism is still unclear. Our previous study found that pilL gene encoding type IV-like pilus probably plays a key role in the colonization of K. pneumoniae in human gastrointestinal tract. Therefore, in this study, we intend to construct pilL gene knockout strains using K. pneumoniae ST11 strains, the differences on the bacterial activity, biofilm formation, etc were compared between the wild-type and knockout strains to analyze the biological effect of pilL gene on K. pneumoniae ST11; The effect of pilL gene on bacterial colonization ability will be further verified by cell adhesion and invasion experiments as well as in the mouse colonization experiment; On this basis, the pathological changes of gastrointestinal mucosa colonized by the bacteria will be observed, and the transcription and expression levels of inflammatory factors will be further investigated to analyze the effect and the key mechanism of pilL gene on the colonization of K. pneumoniae ST11 in the gastrointestinal tract. The implementation of this study will provide theoretical basis and new ideas for the prevention and control of carbapenem-resistant Klebsiella pneumoniae.