Excellence in Research: Antibiotics in the rhizosphere and resistance mechanisms in plants

本项目的目的是研究金属吸收与植物抗生素抗性之间的关系。植物挖掘土壤以提取矿物质，在这样做的过程中，可能会吸收土壤微生物产生的抗生素，对植物的正常功能产生不利影响。植物如何保持足够的营养，同时限制抗生素的吸收是未知的。我们专门研究了模式植物拟南芥的金属吸收及其对抗生素卡那霉素的抗性。我们提出了一个模型，其中各种转运蛋白之间的相互作用解释了金属摄取和抗生素耐药性之间的权衡。我们将数学建模和实验验证相结合的方法将使我们能够检查这些不直观的复杂相互作用。此外，该项目为斯佩尔曼学院的本科生提供了一个极好的跨学科培训机会，斯佩尔曼学院是一所历史悠久的黑人女子学院。总体而言，该计划将通过研究、课程和学生发展机会，为改善教育环境作出贡献。铁和锌是植物中最丰富的微量元素。它们在植物中的吸收和运动受到高度调节。我们的初步结果表明，植物对金属的吸收与抗生素耐药性之间存在联系。最明显的是，暴露于卡那霉素的植物对铁的吸收下降。我们提出了一个模型，将已知的铁和锌的稳态与抗生素卡那霉素的作用结合起来。除铁、锌和卡那霉素外，还考虑了铁和锌的主要螯合剂、柠檬酸盐和烟胺（NA）及其已知或假定的转运体。该模型以木质部装载为中心，木质部装载是养分长距离运输之前的关键步骤。一个相应的基于广义质量作用系统的动态数学模型将被制定并进行计算和生化测试。该模型将为了解拟南芥及其他作物金属营养与抗生素之间的关系提供一个新的范式。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The goal of this project is to investigate the relationship between metal uptake and antibiotic resistance in plants. Plants mine the soil to extract minerals and in so doing, may take up antibiotics produced by soil microorganisms that adversely affect normal plant function. How plants maintain adequate nutrition while limiting the uptake of antibiotics is unknown. We specifically investigate metal uptake in the model plant Arabidopsis thaliana and its resistance to the antibiotic kanamycin. We propose a model in which the interplay among various transporters explains the trade-offs between metal uptake and antibiotic resistance. Our approach that combines mathematical modeling and experimental validation would allow us to examine these otherwise complex interactions that are not intuitive. Moreover the project provides an excellent opportunity for interdisciplinary training of undergraduate students at Spelman College, a Historically Black College for women. Overall, the project will contribute to enhancing the educational environment through research, curriculum and student development opportunities.Fe and Zn are among the most abundant micronutrients found in plants. Their uptake and movement in the plant is highly regulated. Our preliminary results showed a link between metal uptake in plants and antibiotic resistance. Most notably, Fe uptake declined in plants exposed to kanamycin. We propose a model that integrates what is known about Fe and Zn homeostasis with the effects of the antibiotic kanamycin. Besides Fe, Zn and kanamycin, other factors taken into consideration are the main chelators of Fe and Zn, citrate and nicotianamine (NA), and their known or assumed transporters. The model is centered on xylem loading, a critical step prior for the long distance transport of nutrients. A corresponding dynamic mathematical model based on a Generalized Mass Action system will be formulated and tested both computationally and biochemically. It is expected that this model will offer a new paradigm for understanding the link between metal nutrition and antibiotics in Arabidopsis and possibly crop species.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.