DNA限制修饰系统与CRISPR-Cas系统对弯曲菌多重耐药基因岛传播的作用机制

弯曲菌是重要的人畜共患食源性致病菌，近年来因其耐药率的不断上升受到全球人医和兽医临床的高度关注。申请人前期研究发现，我国动物源弯曲菌对常用抗菌药物的耐药多由定位于染色体上、可携带多种外源耐药基因、移动元件及功能基因的多重耐药基因岛介导，其可通过自然转化的方式在弯曲菌种内或种间进行广泛的水平转移。DNA限制修饰系统与CRISPR-Cas系统是细菌抵御外源DNA侵袭的两类主要的免疫防御机制，而弯曲菌中这两类免疫系统对多重耐药基因岛的作用机制尚未阐明。因此本项目拟运用高通量测序、生物信息学、基因编辑等技术，比较DNA限制修饰系统与CRISPR-Cas系统在不同类型弯曲菌中的遗传特征，探明两类系统中的关键突变/基因/序列/对多重耐药基因岛自然转化的调控作用，揭示这两类系统对弯曲菌多重耐药基因岛水平传播的作用机制，为控制多重耐药弯曲菌的传播提供理论依据。

Campylobacter species are major foodborne zoonotic pathogens, which caused widespread concern due to the increasing of antimicrobial resistance. Recently, we demonstrated that the antimicrobial resistance of Campylobacter from animal origin were mainly mediated by the multidrug resistance genomic islands (MDRGIs) in China, which consisted of various resistance genes, mobile elements, and other functional genes from exogenous DNA. The MDRGIs could be horizontally transferred among intraspecies or interspecies. DNA Restriction modification system (RM system) and CRISPR-Cas system were characterized as the major immune system to resist invasion of exogenous DNA in bacterium. However, the mechanism of the two mechanisms action on the MDRGIs in Campylobacter were still unknown. Therefore, using the high-throughput sequencing, bioinformatics, and gene editing technologies, this study aims to compare the characteristic of RM system and CRISPR-Cas system in various isolates, illuminate the mechanism of the two mechanisms action on horizontal transferred of MDRGIs in Campylobacter. Findings in this study will provide theoretical evidence for control the spread of multi-drug resistant Campylobacter.