鸡源沙门氏菌中质粒介导广谱头孢菌素类、多粘菌素类耐药基因（blaCTX-M、mcr-1）共传播机理研究

沙门氏菌是重要的人畜共患病原菌。广谱头孢菌素类是治疗人和动物细菌感染的重要抗生素，blaCTX-M编码超广谱β-内酰胺酶是沙门氏菌对广谱头孢菌素类耐药主要机制。多粘菌素类是人感染G-细菌的最后储存药物，Liu YY等2016首次发现质粒介导多粘菌素耐药基因mcr-1。Rhouma M 2016报道广谱头孢菌素和多粘菌素共耐药，引起世界关注。申请人2016发现鸡源沙门氏菌中携带blaCTX-M、mcr-1基因质粒，介导广谱头孢菌素类和多粘菌素类共耐药。拟采用全基因组测序、转录组测序、CRISPR-Cas、高表达载体等研究携带blaCTX-M、mcr-1基因质粒的流行和遗传结构特征、分析遗传稳定性和适应性代价、寻找关键调控基因和蛋白、探明适应性代偿机制。阐明鸡源沙门氏菌中质粒介导blaCTX-M、mcr-1基因共传播机理和风险，对指导科学用药、控制广谱头孢菌素类、多粘菌素类耐药有重要科学意义。

Salmonella is a significant zoonotic pathogen. Broad-spectrum cephalosporins are very important antimicrobial agents for the treatment of bacterial infection in humans and animals. blaCTX-M encoded extend-spectrum β-lactamases are the predominant mechanism for Salmonella resistant to broad-spectrum cephalosporins. Polymyxin is the last storage of antimicrobials for the treatment of G- bacteria. Liu YY et al. (2016) found the plasmid-mediated polymyxin resistance gene mcr-1 for the first time. Rhouma M (2016) reported co-resistance to both broad-spectrum cephalosporins and polymyxin, which brought about worldwide attention. A plasmid co-harboring blaCTX-M and mcr-1 mediating resistance to broad-spectrum cephalosporins and polymyxin was found by this applicant in chicken-origin Salmonella in 2016. This research will figure out the prevalence and genetic structure of the plasmids carrying blaCTX-M and mcr-1 in Salmonella. hereditary stability and fitness cost will be determined by competition experiment. The critical regulatory genes and proteins in the fitness compensatory mechanism will be sought through transcriptome sequencing, CRISPR-Cas and high expression vector construction. This study will illuminate the co-transmission mechanism of blaCTX-M and mcr-1 and evaluate the transmission risk, which has important scientific significance on the guidance of antimicrobials use and the control of the transmission of broad-spectrum cephalosporins and polymyxin resistance.