目前严重危害我国养牛业的牛出血性败血症病原主要为牛源荚膜血清A型多杀性巴氏杆菌。由于该病原菌间的交互免疫保护率低，临床上主要采用抗生素对牛出血性败血症进行治疗。随着抗生素的广泛及不合理使用，该菌对常用抗生素多重耐药的现象已十分普遍。牛源荚膜血清A型多杀性巴氏杆菌对抗生素耐药可能与染色体基因突变、质粒介导或其主动外排系统过量表达有关。本项目拟对近百株临床分离牛源荚膜血清A型多杀性巴氏杆菌进行耐药性检测，进而对其临床分离多重耐药株的基因组及质粒进行测序、编码基因序列功能预测及功能确证，确定有无染色体基因突变和\或质粒介导的多重耐药机制；通过测定加入质子泵抑制剂前后菌体内含药量变化、采用生物信息学软件分析其可能存在的主动外排系统编码基因及采用荧光定量PCR确证该基因表达水平与其多重耐药水平关系，在一定程度上阐明我国临床分离牛源荚膜血清A型多杀性巴氏杆菌的多重耐药机制，为设法抑制其耐药性奠定基础。

At present, the main pathogen of Cattle hemorrhagic sepsis that serious harming cattle industry in China is bovine capsular serotype A Pasteurella mutocida. Due to the pathogen's lower Interactive immune protective rate, cattle hemorrhagic sepsis was treated mainly by using antibiotics. With the widely and irrational use of antibiotics, the multiple drug-resistance of the bacteria to the common antibiotics has become widespread. Drug-resistance of bovine capsular serotype A Pasteurella mutocida to antibiotics may be linked to chromosome gene mutations, plasmid mediated resistance and excessive expression of efflux systems. The Project intend to test the drug resistance of nearly 100 strains of bovine capsular serotype A Pasteurella mutocida clinical separated, further sequence the genome and plasmid of multiple drug-resistant strains clinical separated, predict the function of its Coding genetic sequence, confirm its function, and finally determine whether there are gene mutations and \ or chromosome plasmid mediated multiple drug-resistant mechanism. Through testing the changes of concentration of drugs in bacteria before and after joining proton pump inhibitor, analyzing the possible efflux system coding genes by using the bioinformatics software, and confirming the gene expression level and its multiple resistance level relations With fluorescent quantitative PCR technology, The Project was intend to clarify to some extent the multiple drug-resistance mechanism of bovine capsular serotype A Pasteurella mutocida clinical separated in China, to lay a foundation for trying to inhibit its resistance.