铁基纳米材料驱动土壤耐药菌敏感性进化的生理及分子机制

土壤抗生素耐药问题日益严重，严重影响粮食安全和生态健康，如何有效防控土壤耐药是当前研究热点。申请人前期研究发现人工纳米材料可作为土壤耐药菌阻控新手段，然而不同结构、性质的纳米材料驱动耐药细菌抗生素敏感性变化的规律和机制尚不清楚。基于此，本项目拟以铜绿假单胞菌为模式菌，构建不同物理化学性质的铁基纳米材料，通过铁基纳米材料理化性质、共存土壤介质影响分析，探索长期进化过程中铁基纳米材料驱动土壤耐药菌敏感变化的作用规律；通过不同胁迫条件下进化菌株抗生素进出细胞过程及细胞屏障结构对比，探明铁基纳米材料驱动土壤耐药菌敏感性进化的生理生化机理；通过抗生素耐受相关基因表达、相互作用及调控网络构建，阐明铁基纳米材料驱动土壤中微生物敏感性进化的分子机制。本项目的研究可为复杂环境中耐药污染控制新策略研发提供科学依据，同时将有助于科学评估实际土壤环境中纳米材料耐药阻控的效能和生态效应。

The increasing prevalence of antibiotic resistant bacteria (ARB) in soil is greatly challenging the food security and ecological health. The proceeds to reduce the propagation of ARB and to avoid the additional generation of ARB are hot-spot issues for the current studies. Our recent study suggested that the long-term exposure of some iron-based nanomaterials to Pseudomonas aeruginosa in soil could induce its sensitive evolution. However, little is known about the behavior and mechanisms of antibiotic sensitivity elevation in bacteria driven by different structures and properties of nanomaterials. In this project, iron-based nanomaterials with various structures and properties will be constructed, and Pseudomonas aeruginosa will be employed as the model bacterium. The effects of physicochemical properties of iron-based nanomaterials and environmental factors on the antibiotic sensitivity evolution in ARB under long-term exposure to nanomaterials will be systemically explored. Based on the comparisons of the processes of antibiotics cellular uptake and efflux as well as the structure of cell barrier in antibiotic-sensitive ARB under different stress conditions, the physiological and biochemical mechanisms regulating the antibiotic sensitivity will be clarified. The expression of antibiotic resistance-related gene and their will interactions will be investigated, and the regulatory network will be constructed to elucidate the molecular mechanisms of iron-based nanomaterials driving the susceptibility evolution of ARB in soil. The outcome of this project will not only provide scientific significance for designing and developing new strategies on the control of ARB in complex environments, but also supply the theoretical basis for the scientific evaluation of the remediation efficacy of nanomaterials toward resistant microbes and their ecological impacts in soil.