目的：通过免疫共沉淀及激光共聚焦试验确定溶血性曼氏杆菌A1及A2血清型LKTA与其受体β2整合素亚单位（CD18）结合域；结合同源模建及分子对接软件模拟系统，筛选溶血性曼氏杆菌新型小分子抑制剂。意义：A1和A2型溶血性曼氏杆菌对羊的致病性不同，除了与其自身的基因序列有关，可能还与其和相应受体的结合位点不同有关，本研究的开展将对A1和A2型溶血性曼氏杆菌致病机理深入研究奠定基础；传统疫苗作用有限，而且溶血性曼氏杆菌对多种药物产生了耐药性，开发新型小分子抑制剂可以作为新的疾病治疗的切入点。方法：免疫共沉淀结合激光共聚焦的体外试验；同源模建结合分子对接的在线模拟软件。创新点：首次采用体外试验结合在线软件模拟相结合的方法，确定溶血性曼氏杆菌LKTA与其受体可能的结合域；针对羊源CD18筛选的溶血性曼氏杆菌小分子抑制剂结构简单，可以体外合成、更经济、更环保，可能代替传统疫苗的作用。

OBJECTIVE: To determine the binding domains of LKTA and its receptor β2 integrin subunits (CD18) of Mannheimia haemolytica Serotype A1 and A2 by co-immunoprecipitation and laser confocal microscopy; to combine homology modeling and molecular docking simulation software systems for screening Mannheimia haemolytica novel small molecule inhibitors. SIGNIFICANCE: The pathogenicity of Serotype A1 and A2 of Mannheimia haemolytica to sheep is different. Apart from its own genetic sequence, it may also be related to the different binding sites of the corresponding receptors. The development of this study will be lay the foundation for the in-depth study of the pathogenic mechanism of Serotype A1 and A2 of Mannheimia haemolytica; traditional vaccines have limited effects, and Mannheimia.haemolytica has developed resistance to various drugs, so the development of novel small molecule inhibitors can serve as the starting point for new disease treatment. METHODS: Co-immunoprecipitation combined with laser confocal in vitro assays; homology modeling combined with molecular docking on-line simulation software. INNOVATION: Testing In vitro combined with online simulation software was used to determine the possible binding domains of LKTA and its receptors in Mannheimia haemolytica; the small molecular inhibitor of Mannheimia haemolytica against hemophilic CD18 was simple in structure and could synthesis in vitro ,more economical and more environmentally friendly, may replace the role of traditional vaccines.