广泛耐药MRSA在各地医院、社区及养殖场传播，已成为一个全球性严重公共卫生问题。质粒、转座子及SCCmec等可移动遗传元件是其广泛耐药的分子基础。课题组前期研究发现CRIPSR系统作为细菌防御外来遗传元件的免疫系统参与细菌耐药调控，但机制不明。本研究依托全国细菌耐药监测网和食源性致病菌监测网收集菌株及资料，通过耐药性分析、耐药遗传元件检测、分子分型及质粒接合等手段，研究广泛耐药MRSA在临床及食品中流行特征及耐药播散规律；通过体外抗生素处理，观察细菌耐药表型、SCCmec结构和CRISPR序列及Cas蛋白表达情况，探讨CRISPR系统对细菌耐药调控机制；通过对不同时空及来源代表性菌株全基因组测序、系统发生分析及种群结构重建，探讨广泛耐药菌遗传进化规律。课题将耐药菌监测与分子流行病学研究相结合，揭示其种群特征、流行规律、传播机制及遗传进化特征，为综合干预广泛耐药MRSA防控关键技术提供依据。

The extensive spread of extensive drug resistant MRSA (XDR-MRSA) in hospitals, communities and livestock farms has become a serious global public health problem. Mobile genetic elements such as plasmids, transposons, and SCCmec are the molecular basis for this wide resistance. Our previous study found that CRIPSR system, as an immune bacterial defense system against foreign genetic elements, is involved in the regulation of bacterial drug resistance, though the mechanism is unclear. This study relies on the China Antimicrobial Resistance Surveillance System and Foodborne Pathogens Monitoring System for isolates and data to study epidemiological characteristics and transmission patterns of XDR-MRSA in clinical and food through drug resistance analysis, genetic component detection, molecular typing and plasmid conjugation. The in vitro antibiotic treatment, bacterial resistance phenotype, SCCmec structure, CRISPR sequence and Cas protein expression will be observed to explore the mechanism of bacterial resistance regulation of CRISPR system; through genome sequencing, phylogenetic analysis and population structure reconstruction of representative strains from different time, space and sources to explore laws of evolution of XDR bacteria. This project combines drug resistance monitoring with molecular epidemiology to reveal its population characteristics, epidemic regularity, transmission mechanism and genetic evolution characteristics and to provide a basis for comprehensive intervention of key technologies for XDR-MRSA prevention and control.