Dynamics of Antimicrobial Resistance in the Urban Water Cycle in Europe

病原菌对抗生素和其他抗菌剂的抗药性在地球各地都在增加。这正逐渐使我们目前的抗生素毫无用处，可能会将患者的生命置于危险之中，因为一些人无法再通过可用的治疗方案进行治疗。抗药性不仅在使用抗生素治疗人时选择在人体内，而且在医院患者或家中病人的抗生素进入污水后也会选择。此外，耐药基因可以转移到其他细菌，在那里它们可以持续存在，并最终转移回病原菌。这种转移也发生在污水中。我们推测，城市供水系统，即下水道、污水处理厂和接收水，是病原菌和环境细菌之间耐药基因交换的中心场所，因为这些系统不断从许多来源接收排泄的抗菌剂、耐药细菌和耐药基因。此外，这些系统中细菌的数量很多，增加了不同细菌之间的耐药性基因转移。由于多种抗生素、杀生剂和重金属的同时存在，不同废物(例如医院和社区污水)的混合增加了对携带多个耐药基因的细菌的选择。DARWIN(欧洲城市水循环中的抗菌剂耐药性动力学)将是第一个跨欧洲检查主要耐药细菌和耐药基因在医院和社区废物排放的超临界水系统中的命运的项目，包括在下水道集水区和接收水的不同阶段耐药基因转移的机制。我们将重点关注耐药基因的传播，这些基因是目前最有问题的基因之一，因为它们对最新一代的抗生素(超广谱β-内酰胺酶(ESBL)和碳青霉烯酶基因)具有耐药性。具体地说，我们将在三个使用抗生素和污水管理做法不同的国家调查这些耐药性类别：丹麦、西班牙和英国。我们推测，在城市供水系统中，抗药性基因很容易从人类排泄物中的致病和非致病“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，环境细菌携带耐药基因穿越更广泛的环境，增加社区暴露。因此，我们将首次确定哪些特定细菌在城市供水系统中携带抗药性基因，并确定抗药性基因转移事件发生在哪里。我们的最终目标是评估耐药基因因环境暴露而返回人类的相对风险。为了指导风险评估，将开发一个城市供水系统的预测性动态数学模型，以帮助做出健康和污水管理决策。

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.