沙门氏菌、大肠杆菌和肺炎克雷伯菌是重要的人畜共患病原菌，抗菌药物使用导致多重耐药严重。申请人分离的沙门氏菌多重耐药率达53.77%；申请人在大肠杆菌、肺炎克雷伯中检出多种耐药基因；申请人2016-2018年报道了细菌重要可移动遗传元件IncA/C质粒、ICEs和Tn7-like元件分别携带15，5，18种耐药基因。IncA/C质粒、ICEs、Tn7-like元件的演化、传播与多重耐药菌产生和传播的相关性亟待解决。本项目拟在前期研究基础上，研究IncA/C质粒、ICEs、Tn7-like元件分布，基于全基因组测序发现新亚型，采用贝叶斯模型分析演化过程；通过比较基因组学分析，阐明元件与多重耐药菌形成和传播关系；采用接合实验、竞争实验和重测序等方法，研究其在多重耐药菌产生和传播中的作用，为防控多重耐药病原菌提供新的理论依据。

Salmonella, Escherichia coli, Klebsiella pneumonia are important zoonotic pathogens, the extensive use of antimicrobial agent caused the emergence of multidrug resistance. The applicant has found that 53.77% of salmonella isolates confer multidrug resistance phenotype, and Escherichia coli, Klebsiella pneumonia isolates carried multiple resistance genes in a survey of antimicrobial resistance. IncA/C plasmids, ICEs and Tn7-like elements are important mobile genetic elements, which harbor multiple resistance genes mediating the transmission of multidrug resistance in animal pathogens. The applicant has also discovered a new IncA/C plasmids, ICEs and Tn7-like elements from pathogens of chicken and swine origin in 2016-2018, which carries15, 5, 18 different resistance genes, respectively. The evolution and dissemination of these mobile genetic elements as well as the formation and transmission mechanism of multidrug resistance pathogens remain to be solved. Based on the previous works, the project plans to investigate the prevalence of IncA/C plasmids, ICEs and Tn7-like elements, try to discover new mobile genetic elements subtypes and analyze the evolution process using Bayesian model. The comparative genome sequence analysis will be used to illuminate the formation and transmission relationship between the elements and multidrug resistance pathogens. Conjugation, competition test and re-sequencing will be used to study their roles in formation and transmission of multi-drug pathogens, which would provide important evidence for preventing and controlling multidrug resistance zoonotic pathogens.