PIRE: Halting Environmental Antimicrobial Resistance Dissemination (HEARD)

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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.