Characterising the sources and drivers of environmental resistomes over UK landscapes and assessing mitigation under different hydrological regimes

抗生素耐药性（AMR）是指对抗生素产生耐药性的微生物，正在成为一个全球性问题。根据最近对AMR的审查，预计耐药感染将导致1000万人死亡，以及约100万亿美元的经济负担（奥尼尔，2014）。这与抗生素耐药菌（ARB）和抗生素耐药基因（ARG）的广泛和快速传播有关。例如，新德里Meta-内酰胺酶-1蛋白（编码blaNDM-1）使细菌对一系列β-内酰胺抗生素如青霉素具有抗性，该蛋白于2008年首次在印度发现，并且此后已从高北极的土壤中回收（McCann等人，2019年）。尽管存在一定程度的内在抗性，但高丰度的抗性归因于人为来源。由于人口稠密地区的污染，AMR的来源往往难以区分，但主要来源包括废水处理厂和农业，这两者都对河流和周围景观造成污染。来自风暴事件的高河流流速已经导致抗性基因丰度的增加，这可能是由于扩散污染（Garner等人，2017年）。随着气候变化导致更多的热浪和降雨事件落在英国的正常季节模式之外，目前还不清楚这将如何影响ARB和ARG在景观中的传播。因此，了解不同水文条件下的源的贡献是重要的。该博士项目调查了导致AMR在英国不同水文制度下传播的来源的贡献，旨在了解AMR在英国景观中的复杂性。英国环境署选择了英国的河流集水区进行进一步研究，这些集水区有不同程度的人类和废物暴露，并反映了高污染和低污染水平。这是坎布里亚郡的伊甸园和诺森伯兰郡的Coquet。了解这些集水区将需要在对比高流量和低流量的情况下对土壤和水进行采样。采集的样本分析将包括使用高通量qPCR定量大量ARG和细菌。该项目的一个较新颖的方面是使用“源跟踪”作为一个将下游汇与其源联系起来的方案。这将被用来估计在高流量和低流量情况下各种干预措施的影响，为环境、食品和农村事务部等决策者提供有用的信息。最终，该项目将通过对英国各地AMR的详细描述，回答哪些干预措施对限制抗生素耐药性传播最有用的问题。Garner，E.（2017）“城市河流中抗生素抗性基因的雨水负荷”，水研究。Elsevier Ltd，123，pp. 144-152. doi：10.1016/j.watres.2017.06.046.McCann，C. M.（2019）“了解高北极土壤生态系统中抗生素抗性基因的驱动因素”，国际环境。Elsevier，125（November 2018），pp. 497-504.土井：10.1016/j.envint.2019.01.034.O 'Neill，J.（2014）“抗生素耐药性综述”，抗菌素耐药性：应对国家健康和财富危机。Wellcome Trust.

Antimicrobial Resistance (AMR) refers to microbes that become resistant to antibiotics and is becoming a global problem. According to a recent review on AMR, infections that are resistant to treatment are projected to result in 10 million deaths, as well as a financial burden of ~US$100 trillion (O'Neill, 2014). This is related to the wide and rapid spread of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARG)s. For example, the New Delhi meta- -lactamase-1 protein (coded blaNDM-1) which makes bacteria resistant to a range of beta-lactam antibiotics such as penicillin, was first discovered in 2008 in India and has since been recovered from soils in the High Arctic (McCann et al., 2019). Despite there being some level of intrinsic resistance, high abundance of resistance are attributed to anthropogenic sources. Due to pollution in populated areas, the sources of AMR are often difficult to distinguish, but the main sources include wastewater treatment plants and agriculture, which both contribute to pollution in rivers and surrounding landscapes. High river flow rates from storm events have resulted in an increase in the abundance of resistance genes, potentially due to diffuse pollution (Garner et al., 2017). With climate change causing more heatwaves and rainfall events falling outside normal seasonal patterns in the UK, it is currently unclear how this will influence the dissemination of ARB and ARGs in a landscape. Therefore understanding the contribution of sources under different hydrological conditions is important. This PhD project investigates the contribution of sources that result in the spread of AMR in the UK under different hydrological regimes, aiming to understand the complexity of AMR across UK landscapes. The Environment Agency has selected river catchments in the UK for further study that have different levels of human and waste exposure and are reflective of high and low levels of pollution. These are the Eden in Cumbria and the Coquet in Northumberland. Understanding these catchments will require sampling campaigns of soil and water under contrasting high and low flow regimes. Analysis of the collected samples will include quantifying a large number of ARGs and bacteria using High throughput qPCR. One of the more novel aspects of this project is the use of SourceTracker as a programme to associate downstream sinks with their sources. This will be used to estimate the impact of various interventions under high and low flow regimes, providing useful information for policy makers, such as the Department for Environment, Food and Rural Affairs (DEFRA). Ultimately, this project will answer the question as to which interventions are most useful to limit the spread of antibiotic resistance, through a detailed characterisation of AMR across UK landscapes. Garner, E. et al. (2017) 'Stormwater loadings of antibiotic resistance genes in an urban stream', Water Research. Elsevier Ltd, 123, pp. 144-152. doi: 10.1016/j.watres.2017.06.046.McCann, C. M. et al. (2019) 'Understanding drivers of antibiotic resistance genes in High Arctic soil ecosystems', Environment International. Elsevier, 125(November 2018), pp. 497-504. doi: 10.1016/j.envint.2019.01.034.O'Neill, J. (2014) 'Review on AMR', Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. Wellcome Trust.