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

最近，天然水中抗生素化合物的威胁日益增长，以及这些水域中微生物对抗生素的耐药性已被认识到，并成为一个新兴的密集研究领域。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，植物还通过接合反应代谢包括抗生素在内的有机化合物，产生隔离在细胞壁和液泡中的植物代谢物。这项拟议项目的总体目标是阐明当植物被食用时，抗生素植物代谢物的产生及其随后在人体系统中的释放。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的结合来代谢抗生素，形成植物结合物，这些结合物被人类消化还原为母体抗生素。为了验证这一假说，本研究将：1.在灭菌、控制系统中鉴定拟南芥中抗生素的代谢物。2.量化种植了海棠和三种蔬菜的土壤系统中抗生素的植物代谢物的产生，这与抗生素在作物系统中的环境命运有关。3.阐明抗生素植物代谢物在人体消化过程中的降解途径。这项拟议的研究解决了现有研究通过结合使用放射性标记的化学品和质谱学来研究抗生素命运的局限性，这将有助于在受控的中微体和柱状研究中量化植物代谢和植物代谢物的降解。因此，拟议的研究有望通过以下成果促进对新出现污染物的植物代谢的了解：(1)开发一个普遍的、可转移的植物代谢模型，(2)对植物系统中抗生素的植物代谢物质量的现实估计，包括对隔离在液泡和细胞壁中的单个植物代谢物随时间的量化，以及(3)确定蔬菜消费期间隔离的植物代谢物的生物利用度。这项研究将通过将发现与教学相结合、让代表性不足的群体参与、广泛传播成果以及应对环境和人类健康挑战来广泛影响社会和科学。研究将吸引和培训一名研究生、至少两名本科生和至少四名高中生进行超越工程学和生物学的积极研究。这个项目将让少数族裔高中生参与研究，以鼓励他们对工程职业的兴趣。研究成果将通过学术途径广泛传播，包括期刊出版物和会议。

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.