鸟类迁徙介导的环境抗生素抗性散播及内在机制研究

The serious dissemination of antibiotic resistance in environment has largely exceeded the previous judgments. Birds, especially the migratory birds, can be potential environmental spreaders of antibiotics resistance. Their activities can mediate remote transportation of environmental antibiotic resistance, construct the interconnection between environmental compartments of different antibiotic resistance (AR) levels and AR compositions, and even bring the antibiotic resistance to unfrequented wild zone. The amount of migratory birds worldwide is as huge as about 5 billion, the coverage area of the migration is so wide including all continents even Antarctica. As a special dissemination mode of antibiotic resistance in environment, the transportation of antibiotic resistance in environment mediated by migratory birds' activities and its intrinsic mechanism are lack of systematic study. In this research, systematic studies will be pointed to this special environmental dissemination mode of antibiotic resistance. The assessment and comparison of antibiotic resistance levels of different environmental compartments in relation to the habitat of migratory birds will be adopted to understand the direction and trend of resistance transmission. Homological analysis of environmental bacterial indicators and polymorphism analysis of antibiotic resistance genes among different environmental compartments will be preformed to disclose the intrinsic carriers in resistance transportation (resistant bacteria or resistance genes). Thereafter, the mobility of the environmental antibiotic resistance gene will be tested to verify the role of horizontal gene transfer on environmental dissemination of antibiotic resistance. The study is aimed to complement the whole picture of environmental dissemination of antibiotic resistance with an important patch, and provide theoretical basis for monitoring and controlling the antibiotic resistance in environment.

环境中抗生素抗性散播的严重程度远远超过了人们之前的判断。鸟类，特别是迁徙鸟类的活动可以介导环境抗生素抗性的远程传播，搭建起具有不同抗生素抗性水平及组成的环境区划间的联系，甚至将抗生素抗性带至人迹罕至的蛮荒地带。全球迁徙鸟类数量之巨，约50亿；其迁徙路径覆盖区域之广，包括甚至南极洲在内的所有大洲。作为一种特殊的环境抗生素抗性散播模式，鸟类迁徙介导的环境抗生素抗性散播及其内在机制缺乏系统性研究。本项目将针对这一特殊的环境抗生素抗性散播模式开展系统研究。通过鸟类生境不同环境区划的抗性评估及比较了解抗性传递方向及趋势；结合不同环境区划间指示菌的同源性及抗性基因的多态性分析探明抗性传递的实质性载体（抗性菌或者抗性基因本身）；通过验证环境抗性基因的可移动性揭示基因水平转移在环境抗生素抗性散播中的作用。本研究旨在为环境抗生素抗性总体散播机制补上重要的一环，并为环境抗生素抗性的监测与控制提供理论依据。

作为抗生素广泛使用甚至滥用的直接后果，抗生素抗性已经成为切切实实的环境问题。如何有效管控，以恢复抗生素的临床效用，需要坚实的理论依据来指导。本项目以候鸟迁徙介导的抗生素抗性环境散播为切入点进行了一系列重要的研究并获得了如下一些主要的研究结果。（1）野生鸟类确实能介导抗生素抗性的环境散播，在此过程中，抗生素抗性基因的水平转移是抗性散播的主要内在机制。（2）插入序列招募抗性基因形成可移动的复合转座子，是抗性基因水平转移的重要机制之一；宿主菌的同源重组系统广泛地参与了复合转座子的重定位。（3）抗性基因高度的可移动性意味着其在宿主菌基因组中的不稳定性，严格控制抗生素的环境排放有望逆转具有高适应性代价的可移动抗性基因的环境丰度。（4）候鸟能够介导环境抗生素抗性的跨区域传播，其抗性决定子的遗传特性（高共选择性和高可移动性）暗示，在适当的选择性压力下候鸟体内的抗生素抗性能够在受体环境形成快速的散播；候鸟在环境抗生素抗性散播中的作用值得更多的关注。