耐甲氧西林金黄色葡萄球菌（MRSA）是医院和社区感染的超级多耐药细菌，但本世纪初在欧洲发现了家畜相关MRSA（LA-MRSA）可以导致人感染发病，相继发现LA-MRSA在全球的家畜中传播，猪是重要的储存宿主，在欧美MRSA的遗传进化和传播中扮演重要角色。中国和英国（尤其是中国）是养猪业大国，LA-MRSA在中英猪群中均有报道，但缺乏深入系统的流行病学研究。本项目与英国剑桥大学合作，运用流行病学、微生物学、分子生物学、基因组学（包括染色体构象宏基因组学）等技术，在至少100个猪场进行猪及相关人群的MRSA分离鉴定和基因组分析，构建转座子突变体库并进行宿主特异性研究，以阐明LA-MRSA在中英猪-人间的流行现状、传播途径及其与饲养管理和临床用药之间的关系，LA-MRSA的群体基因组生物学特征、宿主特异性和致病性的分子机制，毒力和耐药基因的传播与进化，为MRSA感染与传播的防治提供理论依据。

Methicillin-resistant Staphylococcus aureus (MRSA) is considered as one of the most important multidrug resistant ‘superbugs’ causing nosocomial and community-associated infections. Recently, a specific lineage found in European livestock can infect human and cause serious disease. This lineage designated to be ‘livestock-associated MRSA’ (LA-MRSA) has spread among livestock globally, and is now transferring back to humans leading to both colonization and disease. Pigs constitute a large reservoir for LA-MRSA and contribute to an ongoing spread and genetic adaptation in Europe and North America. China and the UK (esp. China) are important countries in pig industry. Both ST9 and ST398 LA-MRSA have been reported in both China and the UK suggesting that both lineages may be established in both countries. However, the molecular epidemiology of LA-MRSA has not been comprehensively studied in either China or the UK. In collaboration with University of Cambridge this project will use the approaches of epidemiology, microbiology, molecular biology, conventional genomics and recently-established chromosome conformation metagenomics to investigate LA-MRSA in China and the UK. A minimum of 100 pig farms (environments, pigs and farm workers) will be surveyed. LA-MRSA isolates will be sequenced. Transposon mutant libraries of representative stains will be constructed and screened by host specificity assays. The aims of this project are to identify the prevalence and transmission pathways of LA-MRSA in the pig farms and hospitals of China and the UK, and their relationship with husbandry and management factors and the usage of antibiotics; to understand the phylogenetic structure of the genomes of LA-MRSA isolates; to identify the host specificity markers and virulence factors; and to understand the dynamics of antimicrobial resistance genes in the LA-MRSA strains. This understanding will inform the development of strategies to reduce the impact of LA-MRSA on human health.