Dynamics of Antimicrobial Resistance in the Urban Water Cycle in Europe

致病菌对抗生素和其他抗菌素的耐药性在地球上到处都在增加。这使我们目前的抗生素逐渐变得无用，可能使患者的生命处于危险之中，因为有些患者无法再通过现有的治疗方案得到治疗。耐药性不仅在抗生素用于治疗人时在人体内被选择，而且在医院患者或家中病人的抗生素进入污水后也被选择。此外，抗性基因可以转移到其他细菌，在那里它们可以持续存在并最终转移回致病菌。这种转移也发生在污水中。我们假设城市供水系统，即下水道、污水处理厂和接收水，是致病细菌和环境细菌之间抗性基因交换的中心场所，因为这些系统不断地从许多来源接收排出的抗菌素、抗性细菌和抗性基因。此外，这些系统中大量的细菌增加了抗性基因在不同细菌之间的转移。由于同时存在各种抗生素、杀菌剂和重金属，不同废物（例如医院和社区污水）的混合增加了携带多种耐药基因的细菌的选择。DARWIN（欧洲城市水循环中抗菌素耐药性动态）将是第一个对医院和社区排放的废物产生的UWSs中关键耐药细菌和耐药基因的命运进行跨欧洲检查的项目，包括在下水道集水区和接收水的不同阶段中耐药基因转移的机制。我们将重点关注耐药基因的传播，这些基因目前是最成问题的基因之一，因为它们赋予了对最新一代可用抗生素的耐药性（扩展谱β -内酰胺酶（ESBL）和碳青霉烯酶基因）。具体而言，我们将在丹麦、西班牙和英国这三个在抗生素使用和污水管理做法方面存在差异的国家调查这些耐药等级。我们假设，在城市供水系统中，抗性基因很容易从人类粪便中的致病性和非致病性“肠道”细菌（在使用抗生素后）传播到更适应下水道环境的环境细菌。然后，环境细菌在更广泛的环境中携带抗性基因，增加了社区暴露。因此，我们将首次确定哪些特定细菌在城市水系中携带抗性基因，并确定抗性基因转移事件发生的位置。我们的最终目标是评估由于环境暴露，抗性基因返回人类的相对风险。为了指导风险评估，将为城市供水系统开发一个预测动态数学模型，以协助卫生和污水管理决策。

Resistance of pathogenic bacteria to antibiotics and other antimicrobials is increasing everywhere on Earth. This is making progressively our current antibiotics useless, potentially placing patient's lives at risk as some can no longer be treated by available treatment options. Resistance is not only selected inside the human body when antibiotics are used to treat people, but also selected after the antibiotics from patients in hospitals or ill people at home are entering the sewage. Moreover, the resistance genes can transfer to other bacteria, where they can persist and eventually transfer back to pathogenic bacteria. This transfer also happens in the sewage. We postulate that urban water systems, that is, sewers, sewage treatment plants and receiving waters, are central places of exchange of resistance genes between pathogenic bacteria and environmental bacteria because these systems continuously receive excreted antimicrobials, resistant bacteria and resistance genes from many sources. Further, the high numbers of bacteria in these systems increases the transfer of resistance genes between different bacteria. The mixing of different wastes (e.g., hospital and community sewage) increases the selection for bacteria carrying multiple resistance genes due to the simultaneous presence of various antibiotics, biocides, and heavy metals.DARWIN (Dynamics of Antimicrobial Resistance in the Urban Water Cycle in Europe) will be the first project to perform a cross-European examination of the fate of key resistant bacteria and resistance genes in UWSs resulting from discharged hospital and community wastes, including mechanisms of resistance gene transfer in different stages of sewer catchments and receiving waters. We will focus on the spread of resistance genes that are amongst the most problematic now because they confer resistance to the latest generation of antibiotics available (genes for extended spectrum beta-lactamases (ESBL) and carbapenemases). Specifically, we will investigate these resistance classes in three countries that differ in their use of antibiotics and sewage management practices: Denmark, Spain and the UK. We postulate that resistance genes readily transmit in urban water systems from pathogenic and non-pathogenic "gut" bacteria in human wastes (after antibiotic use) to environmental bacteria better adapted to the sewer environment. The environmental bacteria then carry the resistance genes across the wider environment, increasing community exposure. Hence, we will, for the first time, determine which specific bacteria carry the resistance genes across the urban water systems and identify where resistance gene transfer events occur. Our ultimate goal is to assess the relative risk of resistance genes returning back to humans due to environmental exposure. To guide risk assessments, a predictive dynamic mathematical model for the urban water systems will be developed to assist in health and sewage management decisions.