环境中亚致死（Sublethal）剂量重金属诱导耐药菌形成及扩散机制研究

项目名称： 环境中亚致死（Sublethal）剂量重金属诱导耐药菌形成及扩散机制研究

项目编号： No.21507012

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 化学工业

项目作者： 李向阳

作者单位： 复旦大学

项目金额： 20万元

中文摘要： 近年来，细菌耐药性已成为威胁人类健康的全球性问题。越来越多的研究显示，除抗生素外，重金属也可促进细菌耐药性的形成及扩散。环境中重金属污染大多处于对细菌生长没有明显抑制的亚致死剂量（Sublethal dose,即最小抑菌浓度以下），但目前关于亚致死剂量重金属污染对细菌耐药性形成及扩散的影响研究较少，对其作用机制也不清晰。本课题针对亚致死剂量重金属促进耐药基因的形成与扩散展开深入研究，一是研究亚致死剂量重金属通过诱发基因突变形成耐药基因作用机制；二是建立耐药基因水平转移评价模型（转化和接合转移模型），研究亚致死剂量重金属对耐药基因转移效率的影响并阐明其影响机理，从而综合评估亚致死剂量重金属对细菌耐药性的影响机制。本研究对全面认识环境中细菌耐药性污染、完善环境中有毒有害重金属健康风险评估与管理具有重要意义。

中文关键词： 亚致死剂量重金属；耐药基因；基因突变；水平基因转移；影响机制

英文摘要： The emergence of bacterial drug-resistance is a growing problem worldwide. Aside from the misuse of antibiotics, numerous researches have proved that heavy metal can also facilitate the evolution and spreading of drug-resistant bacteria in environments. Generally, the concentrations of heavy metals in environments are sublethal, which are below the minimal inhibitory concentration (MIC) of bacteria. Recent evidences suggest that this is likely to have an important role in the evolution and spreading of drug resistance. However, the actions and mechanisms of sublethal metals on drug resistance remain unclear. In order to comprehensively assess the influences of sublethal level of heavy metals on bacterial drug-resistance, the objectives of the proposed research are: (1) to study the effects and mechanisms of sublethal dose of heavy metals on evolution of drug-resistant genes; (2) to establish transformation and conjugation models for evaluating horizontal transfer of drug-resistant genes, and to explore the influences and mechanisms of sublethal dose of heavy metals on horizontal transfer of drug-resistant genes. The proposed research will be significant in shaping an overall understanding of evolution and spreading of bacterial drug-resistance, and improving the health risk assessment and management of the poisonous and harmful heavy metals in environments.

英文关键词： Sublethal dose of heavy metal;Drug-resistant gene;Genetic mutation;Horizontal gene transfer;Mechanism