基于蛋白质组学和代谢组学的mcr-1基因介导的多粘菌素耐药机制研究

项目名称： 基于蛋白质组学和代谢组学的mcr-1基因介导的多粘菌素耐药机制研究

项目编号： No.31602107

项目类型： 青年科学基金项目

立项/批准年度： 2017

项目学科： 农业科学

项目作者： 李会

作者单位： 中国农业大学

项目金额： 15万元

中文摘要： 近年来，革兰氏阴性菌多重耐药问题越来越严重，导致革兰氏阴性菌引起的感染几乎无药可用。多粘菌素常作为“最后一道防线”用于临床上多重耐药革兰氏阴性菌感染的治疗。mcr-1是新发现的质粒介导的多粘菌素可转移性耐药基因，可在畜禽养殖场、环境、人医临床水平传播。mcr-1基因引起的多粘菌素耐药率逐年升高，且该基因存在着从食物链进入人体的风险，严重威胁着人类健康和公共卫生安全。目前，四大洲很多国家都有mcr-1报道，但关于mcr-1基因的耐药机制研究仍较少。本项目拟从蛋白质组学和代谢组学角度对mcr-1基因介导多粘菌素耐药大肠杆菌耐药株和敏感株进行研究，明确mcr-1基因引起的蛋白谱和代谢谱特征，并对畜禽养殖场采集的携带mcr-1基因且遗传背景相似的大肠杆菌进行生物标志物验证分析，阐明mcr-1基因介导的粘菌素耐药机制，可为临床上规避mcr-1基因的迅速传播和防止耐药性的产生提供科学依据。

中文关键词： mcr-1；多粘菌素；蛋白质组学；代谢组学；耐药机制

英文摘要： In recent years, the rise in infections caused by multidrug-resistant (MDR) Gram-negative bacteria, has led to almost no drug used to cure. And polymyxin was often used clinically as “the last line” to treat the infections caused by MDR Gram-negative bacteria. mcr-1 is a newly discovered plasmid-mediated polymyxin transferable resistance gene and could be transmitted by horizontal transfer from livestock, environment to human beings. The resistant rate of polymyxin caused by mcr-1 gene in animal-derived food was increased year by year and the gene could enter human body through food chain, which seriously threaten to human health and public health security. At present, mcr-1 gene has been disseminated to many countries of four continents. However, there is almost no study on mcr-1 mediated polymyxin resistance mechanisms. This project is going to study mcr-1 gene mediated polymyxin resistant Escherichia coli and susceptible strains using proteomics and metabolomics methods. The aim of this project is to clarify the proteomic and metabolic features related to mcr-1 gene in E. coli and decipher the resistance mechanisms of mcr-1 gene in polymyxin resistance. mcr-1 positive colistin-resistant E. coli strains isolated from livestock which have similar genetic background will be further performed confirmatory analysis of biomarkers. This project will provide scientific basis for avoiding the rapid dissemination of mcr-1 gene and the development of antibiotic agents.

英文关键词： mcr-1;Polymyxin;Proteomics;Metabolomics;Resistance mechanism