| NSF Org: |
CBET Division of Chemical, Bioengineering, Environmental, and Transport Systems |
| Recipient: |
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| Initial Amendment Date: | January 8, 2024 |
| Latest Amendment Date: | January 8, 2024 |
| Award Number: | 2340818 |
| Award Instrument: | Continuing Grant |
| Program Manager: |
Sunny Jiang
cjiang@nsf.gov (703)292-7858 CBET Division of Chemical, Bioengineering, Environmental, and Transport Systems ENG Directorate for Engineering |
| Start Date: | May 1, 2024 |
| End Date: | April 30, 2029 (Estimated) |
| Total Intended Award Amount: | $558,749.00 |
| Total Awarded Amount to Date: | $433,247.00 |
| Funds Obligated to Date: |
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| History of Investigator: |
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| Recipient Sponsored Research Office: |
1 FORESTRY DR SYRACUSE NY US 13210-2712 (315)470-6606 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
1 Forestry Drive Syracuse NY US 13210-2712 |
| Primary Place of
Performance Congressional District: |
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| Unique Entity Identifier (UEI): |
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| Parent UEI: |
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| NSF Program(s): | EnvE-Environmental Engineering |
| Primary Program Source: |
01002425DB NSF RESEARCH & RELATED ACTIVIT |
| Program Reference Code(s): |
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| Program Element Code(s): |
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| Award Agency Code: | 4900 |
| Fund Agency Code: | 4900 |
| Assistance Listing Number(s): | 47.041 |
ABSTRACT
Bacterial antibiotic resistance (AR) infections are among the top 10 threats to global public health. In the United States alone, more than 2.8 million bacterial AR infections are reported each year, causing at least 35,000 deaths and approximately $55 billion in economic losses. Bacterial AR has an environmental origin, develops, and transmits within and between ecosystems and poses a risk to human health through environmental exposure and/or ingestion of food and drinking water. Recent studies have established that horizontal gene transfer (HGT) that mediates DNA exchange between individual cells not connected by inheritance is pivotal in controlling the development and transmission of antibiotic resistance genes (ARGs) in the environment and to bacterial pathogens of clinical relevance. The overarching goal of this CAREER project is to design, develop and evaluate new solutions to mitigate and curb the transmission of AR genes in agricultural soils and their potential transfer to pathogens via HGT. To advance this goal, the Principal Investigator proposes to test the hypothesis that 1) mixtures of non-antibiotic micropollutants (NAMPs) at environmentally relevant concentrations promote the transmission of ARGs in agricultural soils via HGT and 2) this adverse outcome can be mitigated by inhibiting the type IV secretion system (T4SS), the biological assembly that mediates HGT in prokaryotes, using the natural product rottlerin. The successful completion of this project will benefit society through the generation of new fundamental knowledge to advance the design and deployment of more cost-effective and sustainable solutions to mitigate and prevent the development and transmission of ARGs in agricultural soils. Additional benefits to society will be achieved through student education and training including the mentoring of one graduate student and one undergraduate student at the State University of New York College of Environmental Science and Forestry.
Horizontal gene transfer (HGT) plays an essential role in antibiotic resistance (AR) dissemination and is at the heart of the challenge associated with the risk of environmental reservoirs of antibiotic resistance genes (ARGs). Escalated HGT in hotspots during hot moments such as agricultural soils receiving manure or biosolids represents a significant risk. Although a broad range of non-antibiotic micropollutants (NAMPs) have now been detected in raw and treated manure biosolids and soils receiving manure or biosolids, little is known about the impact of these micropollutants on HGT-mediated transmission of ARGs in agricultural soils. This CAREER project will address these critical knowledge gaps. The specific objectives of the research are to 1) develop a mechanistic understanding of NAMP-induced HGT in model agricultural soils (alfisols and mollisols) by combining model-assisted quantification and transcriptome analysis; (2) identify eco-evolutionary controls of the scope of NAMP-induced HGT in the model agricultural soils by combining multi-omics analyses, microfluidic-assisted in situ observations and data science, and; (3) demonstrate the effectiveness of rottlerin (a polyphenol natural product) as a broad-spectrum inhibitor of HGT in agricultural soils; and (4) elucidate the molecular-to-community mechanisms of the HGT mitigating effect of rottlerin in agricultural soils and complex microbial systems with a focus on network interactions. The successful completion of this project has the potential for transformative impact through the generation of new fundamental knowledge to advance the design and implementation of cost-effective solutions to control and mitigate NAMP-induced HGT of ARGs in agriculture soils. To implement the educational and training goals of this CAREER project, the Principal Investigator (PI) proposes to leverage ongoing programs at the State University of New York College of Environmental Science and Forestry (ESF) and collaborations with multiple partners in Upstate New York to (1) develop an interdisciplinary curriculum that implements team science to foster cross-disciplinary collaboration among ESF students and 2) design and deliver a vertically integrated summer program (SMILE HEART UP) to broaden participation in STEM. In addition, the PI plans to leverage the research findings from this project to design high school course modules and organize a workshop for teachers to facilitate the dissemination of the education modules across the State of New York.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
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