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耐药性在地球上任何地方都在增加。这使得我们目前的抗生素逐渐变得无用，可能会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进行治疗。耐药性不仅在使用抗生素治疗时在人体内选择，而且在医院病人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，并最终转移回致病菌。这种转移也发生在污水中。我们假设，城市水系统，即下水道，污水处理厂和接收沃茨，是病原菌和环境细菌之间的耐药基因交换的中心场所，因为这些系统不断接收排泄的抗菌剂，耐药细菌和耐药基因从许多来源。此外，这些系统中的大量细菌增加了不同细菌之间的抗性基因转移。不同废物的混合（例如，医院和社区污水）中同时存在各种抗生素、杀生物剂和重金属，增加了对携带多种抗性基因的细菌的选择。（欧洲城市水循环中抗菌素耐药性的动态）将是第一个跨欧洲检查UWS中主要耐药细菌和耐药基因命运的项目，这些耐药细菌和耐药基因来自排出的医院和社区废物，包括抗性基因在污水集水区和受纳沃茨不同阶段的转移机制。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，因为它们赋予了对最新一代抗生素的耐药性（超广谱β-内酰胺酶（ESBL）和碳青霉烯酶的基因）。具体来说，我们将调查这些耐药类在三个国家，不同的抗生素的使用和污水管理的做法：丹麦，西班牙和英国。我们假设，耐药基因很容易在城市供水系统中传播，从人类粪便中的致病性和非致病性“肠道”细菌（抗生素使用后）到更好地适应下水道环境的环境细菌。然后，环境细菌携带抗性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的细菌在城市供水系统中携带耐药基因，并确定耐药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而导致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性动态数学模型，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.