CAREER: Systems Microbiology and InterdiscipLinary Education for Halting Environmental Antibiotic Resistance Transmission (SMILE HEART)

职业：阻止环境抗生素耐药性传播的系统微生物学和跨学科教育（SMILE HEART）

• 批准号: 2340818
• 负责人: Yaqi You
• 金额: $ 55.87万
• 依托单位: SUNY College of Environmental Science and Forestry
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-05-01 至 2029-04-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2340818&HistoricalAwards=false
• 关键词: CAREER; Systems; Microbiology; InterdiscipLinary; Education

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.

细菌抗生素耐药性(AR)感染是全球公共卫生面临的十大威胁之一。仅在美国，每年报告的细菌性AR感染就超过280万例，造成至少3.5万人死亡和约550亿美元的经济损失。细菌AR起源于环境，在生态系统内和生态系统之间发展和传播，并通过环境暴露和/或摄入食物和饮用水对人类健康构成威胁。最近的研究表明，水平基因转移(HGT)在控制环境中抗生素耐药基因(ARGs)的发展和向临床相关的细菌病原体传播方面起着关键作用。HGT介导的是单个细胞之间的DNA交换，而不是通过遗传连接。这一职业项目的总体目标是设计、开发和评估新的解决方案，以减轻和遏制AR基因在农业土壤中的传播及其通过HGT向病原体的潜在转移。为了推进这一目标，首席研究员建议检验以下假设：1)与环境相关的浓度的非抗生素微污染物(NAMPs)的混合物促进农业土壤中的ARGs通过HGT传播；2)这种不利结果可以通过使用天然产物腐菌素抑制IV型分泌系统(T4SS)来减轻，T4SS是原核生物中调节HGT的生物组装。该项目的成功完成将使社会受益，因为它将产生新的基本知识，以推动设计和部署更具成本效益和可持续的解决方案，以减轻和防止农业土壤中ARGs的发展和传播。通过学生教育和培训将获得更多的社会利益，包括指导纽约州立大学环境科学与林业学院的一名研究生和一名本科生。水平基因转移(HGT)在抗生素耐药性(AR)传播中发挥着关键作用，也是与环境中抗生素耐药性基因(ARGs)储存库风险相关的挑战的核心。在热点地区，如农业土壤，接受粪便或生物固体的HGT升高是一个重大风险。虽然现在已经在生的和处理的粪便、生物固体以及接受粪便或生物固体的土壤中检测到了广泛的非抗生素微污染物(NAMPs)，但关于这些微污染物对农业土壤中HGT介导的ARGs传播的影响还知之甚少。这个职业项目将解决这些关键的知识差距。本研究的具体目标是：1)通过模型辅助定量和转录组分析相结合，从机理上理解NAMP诱导的HGT在模式农业土壤中的作用；(2)通过多组学分析、微流控原位观察和数据科学相结合的方法，确定模式农业土壤中NAMP诱导HGT范围的生态进化控制；以及(3)论证多酚天然产物--腐菌素作为农业土壤中HGT的广谱抑制剂的有效性；(4)阐明HGT在农业土壤和复杂微生物系统中减轻腐熟作用的分子-群落机制，重点是网络相互作用。该项目的成功完成有可能产生变革性的影响，通过产生新的基础知识来推进成本效益解决方案的设计和实施，以控制和减轻NAMP引起的农业土壤中ARGs的HGT。为了实现这一职业项目的教育和培训目标，首席调查员(PI)建议利用纽约州立大学环境科学与林业学院(ESF)正在进行的计划以及与纽约州北部多个合作伙伴的合作，(1)开发实施团队科学的跨学科课程，以促进ESF学生之间的跨学科合作；以及(2)设计和提供垂直整合的暑期计划(微笑的心)，以扩大对STEM的参与。此外，PI计划利用这一项目的研究成果来设计高中课程模块，并为教师组织一次研讨会，以促进教育模块在纽约州的传播。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。