质粒介导耐药基因水平散播（质粒接合作用）是导致细菌耐药基因在菌属间广泛散播的最常见途径。IncFII质粒是多重耐药大肠埃希菌中最常见的接合型质粒，它的接合受多种因素的调控，其中全身/局部调节蛋白（如H-NS、CpxAR和TraJ等）的调控作用最为重要。但是，目前调节蛋白调控IncFII质粒接合的机制尚不明晰。本项目拟以多重耐药鸡大肠埃希菌的IncFII质粒为研究对象，通过构建单、双基因缺失株及互补株、构建不同目标基因启动子的P-LacZ融合报告质粒、电泳迁移率变动分析和DNA足迹试验等方法探明H-NS和CpxAR调控IncFII质粒接合作用的靶基因、调控方式及位点，阐述其对IncFII质粒接合的互作调控机制，以期为控制IncFII质粒介导的多重耐药基因水平快速散播提供理论依据，也为研究新药及探寻新的药物作用靶标提供新型策略与手段。

The horizontal gene transfer (HGT) by plasmid conjugations plays an important role in the dissemination of antimicrobial resistance genes. The IncFII plasmid is the most common conjugative one in multi-resistant enterobacteria. H-NS and CpxAR are the main factors to regulating plasmid conjugations. But, it is still unclear on the regulation between H-NS and CpxAR on the IncFII plasmid conjugations. In this proposal, we focus on the IncFII plasmid among multi-drug resistance Escherichia coli isolated from chickens. The strains with target gene deletions are constructed to elucidate the coordinate regulation mechanism. Electrophoretic mobility shift assay (EMSA) and DNA footprinting assay are used to find out the target binding sites and its regulative mechanism on the IncFII plasmid conjugations. Molecular biological methods for the research of H-NS and CpxAR regulative mechanisms on IncFII plasmid conjugations will contribute to control the spread of antimicrobial resistance genes by plasmids, and to provide a new strategy and means for the search of new drug targets and theprevention and control of pathogens 。