Antibiotic chemistry in agricultural soils: modelling mineral-antibiotic interactions from first principles.

农业土壤中的抗生素化学：根据第一原理模拟矿物质-抗生素相互作用。

• 批准号: NE/X009572/1
• 负责人: Helen Chappell
• 金额: $ 10.06万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FX009572%2F1
• 关键词: Antibiotic; chemistry; agricultural; soils; modelling

In this pilot project, we will explore the chemistry of two commonly used veterinary antibiotics (enrofloxacin and florfenicol), and their metabolites, at the surfaces of major soil minerals (kaolinite and goethite), using first principles computational modelling. This will give us an atomic-scale understanding of how these ubiquitous environmental chemicals bond to the mineral components of soil and how competition between different antibiotics can lead to the retention of some drugs in the soil, and the wash-out of others into nearby water courses. This is critically important with respect to the potential development of antimicrobial resistance (AMR) in the environment as well as the direct uptake of contaminants by lower animals and plants and their transfer into the food chain. The European Commission recently released a communication outlining the "European Union Strategic Approach to Pharmaceuticals in the Environment", urgently calling for an improved understanding of the risks of medicinal products in the environment, and noting, in particular, knowledge gaps related to the 'environmental fate of pharmaceuticals' and the presence of 'multiple substances.' Furthermore, in May 2022 the Federation of Veterinarians of Europe held a European Biomedical Policy Forum in Pharmaceuticals in the Environment, concluding that high concentrations of antibiotics and, in particular, their metabolic by-products, pose an urgent world-wide ecotoxicological threat. Veterinary antibiotics, comprising one of the largest groups of pharmaceutical pollutants, are a mainstay of modern farming practice, and as a result, they are now ubiquitous in agricultural soils, being discharged directly to land via animal excretion and through the use of animal manure as an organic fertiliser, the consequences of which remain worryingly opaque. However, antibiotics do not occur in isolation and are part of a chemical cocktail where interactions with other substances can alter their behaviour and risk. It is therefore crucial to understand the complex chemistry of competitive sorption processes that control the mobility and behaviour of antibiotics in soils. Without this understanding a significant knowledge gap exists between chemical availability and potential for antibiotic induced effects. We are therefore focussing this proposal on the unwitting development of a chemical environment that can, downstream, lead to detrimental microbial evolution. We will use first principles geometry optimization and molecular dynamics to calculate the dynamic pathways of antibiotic-surface interactions, revealing which antibiotics or metabolites bond most strongly to the mineral surfaces and what happens to those interactions in the presence of multiple molecules. The aim is, therefore, to establish detailed chemical knowledge that can be used to improve current environmental fate models and bring a more nuanced understanding of how antibiotics, and, ultimately, other emerging contaminants and active pharmaceutical ingredients (APIs), behave in soils. This work will lead to impact on policy around veterinary good-practice, and will provide impetus for bringing the environmental risk assessment for new pharmaceuticals entering the environment, fully up to date and relevant to different environmental scenarios. The research is consistent with a 'One Health' approach that recognises the interconnection of animal, human and environmental health and that by tackling environmental pollutants all three can be positively enhanced. This is an ambitious use of first principles dynamical modelling, but one that is now within scope with advent Tier 1, 2 and 3 computing resources.

在这个试点项目中，我们将利用第一原理计算模型，探索两种常用兽用抗生素（恩诺沙星和氟苯尼考）及其代谢物在主要土壤矿物（高岭石和针铁矿）表面的化学性质。这将使我们从原子尺度上了解这些无处不在的环境化学物质如何与土壤的矿物质成分结合，以及不同抗生素之间的竞争如何导致某些药物保留在土壤中，而其他药物则被冲刷到附近的水中课程。这对于环境中抗菌素耐药性 (AMR) 的潜在发展以及低等动植物直接吸收污染物及其转移到食物链中至关重要。欧盟委员会最近发布了一份通讯，概述了“欧盟环境中药品战略方针”，紧急呼吁加深对环境中药品风险的了解，并特别指出与“环境中的药品”相关的知识差距。药品的命运”和“多种物质”的存在。此外，欧洲兽医联合会于 2022 年 5 月举办了欧洲环境中药物生物医学政策论坛，得出的结论是，高浓度的抗生素，特别是其代谢副产物，对全球范围内的生态毒理学构成了紧迫的威胁。兽用抗生素是最大的药物污染物之一，是现代农业实践的支柱，因此，它们现在在农业土壤中无处不在，通过动物排泄物和通过使用动物粪便直接排放到土地。一种有机肥料，其后果仍然令人担忧地不透明。然而，抗生素并不是孤立存在的，而是化学混合物的一部分，与其他物质的相互作用可能会改变其行为和风险。因此，了解控制土壤中抗生素的流动性和行为的竞争性吸附过程的复杂化学至关重要。如果没有这种了解，化学品的可用性和抗生素诱导效应的潜力之间就会存在重大的知识差距。因此，我们将该提案的重点放在化学环境的无意发展上，这种化学环境可能在下游导致有害的微生物进化。我们将使用第一原理几何优化和分子动力学来计算抗生素与表面相互作用的动态路径，揭示哪些抗生素或代谢物与矿物表面的结合最牢固，以及在多个分子存在的情况下这些相互作用会发生什么。因此，我们的目标是建立详细的化学知识，可用于改善当前的环境命运模型，并更细致地了解抗生素以及最终其他新兴污染物和活性药物成分 (API) 在土壤中的表现。这项工作将对围绕兽医良好实践的政策产生影响，并将推动对进入环境的新药品进行完全最新的环境风险评估并与不同的环境情景相关。该研究符合“同一个健康”方法，该方法认识到动物、人类和环境健康之间的相互联系，并且通过解决环境污染物，这三者都可以得到积极增强。这是对第一原理动态建模的雄心勃勃的使用，但现在已经在第 1 层、第 2 层和第 3 层计算资源出现的范围内。