PIRE: Halting Environmental Antimicrobial Resistance Dissemination (HEARD)

抗菌素耐药性是一种全球性的公共卫生危机，已被宣布为21世纪对人类福祉的最大威胁之一。抗菌素耐药性是指致病生物体对常用治疗药物不再产生反应。阻止抗菌素耐药性是一项复杂的任务，因为抗菌素耐药性的自然背景水平在世界各地各不相同，人类影响抗菌素耐药性的方式有很多，而且自然和人类影响在世界各地以不同的方式相互作用，影响多重抗微生物药物耐药性“超级细菌”的产生和传播。尽管在减少医院产生的耐药性方面作出了大量努力，但抗菌素耐药性的传播仍在继续加速，从而引起了对减少抗菌素耐药性在废水环境中传播和/或传播的新关注。废水处理厂是一个合理的重点，因为它们是来自各种来源（即医院、工业、家庭）的耐药生物和抗微生物化合物的收集点，它们是AMR环境传播的潜在滋生地。抗菌药物和其他化学压力源（例如重金属、杀菌剂）经常进入废水处理厂，可能会选择耐药生物，同时也刺激它们产生和共享导致耐药的DNA元素。该PIRE项目，即停止环境抗菌素耐药性传播[HEARD]，将1)量化废水处理过程如何影响全球废水处理厂样带中抗菌素耐药性的不同方面（例如，抗菌素耐药性药物、抗菌素耐药性生物和潜在抗菌素耐药性的DNA元素），2)确定废水处理厂和接收环境（例如河流、湖泊或管网）的特征如何相互作用以影响抗菌素耐药性的传播。3)开发和测试新的方法来阻止来自污水处理厂的抗菌素耐药性的传播。为该项目组建的国际团队包括来自美国四个机构和其他六个国家（中国、印度、菲律宾、葡萄牙、瑞典和瑞士）的研究人员。该项目的国际层面是至关重要的，因为1)AMR的传播是全球关注的问题，2)抗菌剂的使用和处理以及废水管理实践在一个社会与另一个社会之间存在显著差异，3)国际研究合作为美国学生成为全球参与的美国科学和工程劳动力的一部分做好了准备。假设1：可以监测污水处理厂的进水，以衡量当地抗菌剂的使用和处理做法对耐药生物和耐药元素流行的影响。假设2：全球各地的废水中存在广泛的抗菌素耐药元素和耐药细菌梯度。假设3：可以选择或修改废水处理工艺和接收环境，以减轻抗菌素耐药性的传播。为了解决这些假设并回答这些问题，我们围绕三个研究重点制定了一个全面的研究计划：重点1：抗菌药物、抗生素耐药细菌和废水处理过程中耐药元素命运的全球侦察；重点2：污水处理厂和接收环境在耐药性传播中的相对作用；重点3：推进废水处理技术，用于抗菌药物、耐药细菌和耐药元素的去除。hear汇集了四所美国大学和十所国际学术机构。该项目最初的重点将是在全球范围内跟踪和量化一组选定的目标抗性元素（例如，NDM-1、intI1、blaTEM、vanA和sul1）在美国、亚洲和欧洲的污水处理厂进水和流出物中的浓度。与此同时，项目成员将利用宏基因组学检测非目标耐药元素和细菌。然后，宏基因组信息将指导和改进未来在全球野外样带的目标取样工作。为了解决废水引起的耐药性传播的威胁，该团队将在现场和实验室规模上研究废水处理厂操作变量（例如，F/M比、固体保留时间和好氧/厌氧条件）的变化如何影响耐药细菌和耐药元素。该项目的国际合作伙伴协同为美国的pii学生提供了文化背景，国际研究经验，可以获得世界级的合作者和设施，以及抗微生物药物耐药性和耐药性传播全球威胁方面的独特专业知识。该奖项由美国国家科学基金会工程局化学、生物工程、环境和运输系统部门共同资助。

Antimicrobial resistance (AMR), which occurs when disease-causing organisms no longer respond to the drugs commonly used to treat them, is a worldwide public health crisis and as such has been proclaimed to be one of the greatest threats to human wellbeing of the 21st Century. Halting AMR is a complex task because natural background levels of AMR vary worldwide, there are many ways that humans impact AMR, and because natural and human impacts interact in different ways around the world to influence how multi-antimicrobial resistant "super-bugs" arise and are transmitted. Although substantial effort has focused on lessening hospital-derived resistance, the spread of AMR has continued to accelerate, thus creating new attention to diminishing the spread and/or transmission of AMR in the wastewater environment. Wastewater treatment plants are a logical focus because they serve as collection points for resistant organisms and antimicrobial compounds from a wide variety of sources (i.e., hospitals, industries, households) and they are potential breeding grounds for environmental dissemination of AMR. Antimicrobial drugs and other chemical stressors (e.g., heavy metals, biocides) regularly enter wastewater treatment plants and may select for resistant organisms, while also stimulating them to produce and share the DNA elements responsible for resistance. This PIRE project, Halting Environmental Antimicrobial Resistance Dissemination [HEARD], will 1) quantify how wastewater treatment processes affect different aspects of AMR (e.g., the antimicrobial drugs, AMR organisms, and the DNA elements underlying AMR) across a global transect of wastewater treatment plants, 2) determine how the characteristics of wastewater treatment plants and the receiving environment (e.g., river, lake, or pipe network) interact to affect the spread of AMR, and 3) develop and test novel approaches to stop the spread of AMR originating from wastewater treatment plants. The international team assembled for this PIRE project includes researchers from four U.S. institutions and six other countries (China, India, Philippines, Portugal, Sweden and Switzerland). The international dimensions of this project are essential because 1) the propagation of AMR is of global concern, 2) the use and disposal of antimicrobials and wastewater management practices differ significantly from one society to another, and 3) international research collaboration prepares U.S. students to be part of a globally engaged U.S. science and engineering workforce.Three overarching hypotheses drive HEARD: Hypothesis 1: wastewater treatment plant influents can be monitored to gauge the impacts of local antimicrobial use and disposal practices on the prevalence of resistant organisms and resistance elements. Hypothesis 2: A broad gradient of antimicrobial resistance elements and resistant bacteria are present in wastewater effluents across the globe. Hypothesis 3: wastewater treatment processes and receiving environments can be chosen or modified to mitigate the spread of antimicrobial resistance. To address these hypotheses and answer these questions we have developed a comprehensive research plan organized around three research thrusts: Thrust 1: Global Reconnaissance of Antimicrobial Drugs, Antibiotic Resistant Bacteria, and Resistance Element Fate During Wastewater Treatment; Thrust 2: The Relative Roles of Wastewater Treatment Plants and Receiving Environments in Resistance Dissemination; and Thrust 3: Advancing Wastewater Treatment Technologies for Antimicrobial Drug, Antibiotic Resistant Bacteria, and Resistance Element Removal. HEARD brings together four U.S. universities and ten international academic institutions. The project's initial focus will be to globally track and quantify the concentrations of a select group of target resistance elements (e.g., NDM-1, intI1, blaTEM, vanA, and sul1) within wastewater treatment plant influents and effluents in the U.S., Asia, and Europe. In parallel, the project members will utilize metagenomics to detect nontarget resistance elements and bacteria. The metagenomic information will then direct and refine future targeted sampling efforts across the global transect of field sites. To develop solutions to the threat of wastewater mediated resistance dissemination the team will examine both at field and laboratory scale how changes in wastewater treatment plant operational variables (e.g., F/M ratio, solids retention time, and aerobic/anaerobic conditions) affect both resistant bacteria and resistance elements. The project's international partners synergistically provide the U.S.-based PIRE students with intracultural context, international research experience with access to world-class collaborators and facilities, and unique expertise in antimicrobial resistance and the global threat of resistance dissemination.This award is co-funded by the Division of Chemical, Bioengineering, Environmental, and Transport Systems of NSF's Directorate for Engineering.