UNS: Collaborative Research: Newly and To-Be-Discovered Phytometabolites of Antimicrobials: Importance to Fate in Environmental and Human Systems

UNS：合作研究：新发现的和即将发现的抗菌药物植物代谢物：对环境和人类系统命运的重要性

• 批准号: 1510203
• 负责人: Dawn Dechand
• 金额: $ 30.94万
• 依托单位: Michigan State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1510203&HistoricalAwards=false
• 关键词: UNS; Collaborative; Research; Newly; Discovered

1510203Reinhold1510714BornhorstRecently the growing threat of antibiotic compounds in natural waters and the antibiotic resistance in microorganism in those waters has been recognized and is an emerging field of intense research. The uptake and accumulation of antibiotics by food crops has prompted concerns about unintentional human exposure. In addition to accumulation, plants metabolize organic chemicals, including antibiotics, through conjugation reactions, resulting in phyto-metabolites that are sequestered into cell walls and vacuoles. The overall aim of the proposed project is to elucidate the production of phyto-metabolites of antibiotics and their subsequent release in human systems when plants are eaten.The proposed research will evaluate the central hypothesis that plants predominantly metabolize antibiotics through conjugation with glycosides and glutathione, forming phyto-conjugates that are reverted to the parent antibiotic by human digestion. In order to evaluate this hypothesis, the research will: 1. Identify the metabolites of antibiotics in Arabidopsis thaliana in sterilized, controlled systems. 2. Quantify the production of phyto-metabolites of antibiotics in soil systems planted with A. thaliana and three vegetables, as relevant to the environmental fate of antibiotics in crop systems. 3. Elucidate pathways of degradation of phyto-metabolites of antibiotics during human digestion. The proposed research addresses the limitations of existing research on the fate of antibiotics through coupled use of radiolabeled chemicals and mass spectrometry, which will facilitate quantification of phyto-metabolism and degradation of phyto-metabolites in controlled mesocosms and column studies. Consequently, the proposed research is expected to advance understanding of phyto-metabolism of emerging pollutants through the following outcomes: (1) development of a generalized, transferable model of phyto-metabolism, (2) realistic estimates of the mass of phyto-metabolites of antibiotics in vegetated systems, including quantification of individual phyto-metabolites sequestered in vacuoles and cell walls with time, and, (3) determination of the bioavailability of sequestered phyto-metabolites during consumption of vegetables. This study will broadly impact society and science through integrating discovery and teaching, engaging underrepresented groups, broadly disseminating results, and addressing environmental and human health challenges. Research will engage and train a graduate student, at least two undergraduate students, and least four high school students in active research that transcends engineering and biology. This project will involve minority high-school students in research to encourage interest in engineering careers. Research outcomes will be broadly disseminated through academic avenues, including journal publications and conferences.

近年来，天然水体中抗生素化合物的威胁日益严重，水体中微生物的抗生素耐药性已成为一个新兴的研究热点。粮食作物对抗生素的吸收和积累引发了人们对人类无意接触抗生素的担忧。除了积累外，植物还通过偶联反应代谢有机化学物质，包括抗生素，从而产生植物代谢物，这些代谢物被隔离在细胞壁和液泡中。拟议项目的总体目标是阐明抗生素的植物代谢物的产生及其在食用植物时在人体系统中的随后释放。拟议的研究将评估中心假设，即植物主要通过与糖苷和谷胱甘肽结合代谢抗生素，形成植物偶联物，经人类消化恢复为母体抗生素。为了评估这一假设，本研究将：1。鉴定消毒控制系统中拟南芥中抗生素的代谢物。2. 量化种植拟南芥和三种蔬菜的土壤系统中抗生素植物代谢物的产量，因为这与作物系统中抗生素的环境命运有关。3. 阐明人类消化过程中抗生素植物代谢物降解的途径。该研究通过放射性标记化学物质和质谱联用解决了现有抗生素命运研究的局限性，这将有助于在受控的中生态系统和柱状研究中量化植物代谢和植物代谢物的降解。因此，该研究有望通过以下结果促进对新兴污染物植物代谢的理解：(1)建立一个广义的、可转移的植物代谢模型；(2)对植物系统中抗生素植物代谢物的质量进行现实的估计，包括对液泡和细胞壁中随时间隔离的单个植物代谢物进行量化；(3)确定在食用蔬菜过程中被隔离的植物代谢物的生物利用度。这项研究将通过整合发现和教学、吸引代表性不足的群体、广泛传播结果以及解决环境和人类健康挑战，对社会和科学产生广泛影响。研究将参与并训练一名研究生，至少两名本科生和至少四名高中生进行超越工程和生物学的积极研究。该项目将让少数族裔高中学生参与研究，以鼓励他们对工程职业的兴趣。研究成果将通过学术渠道广泛传播，包括期刊出版物和会议。