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，我们将使用第一原理计算建模。这将使我们对这些无处不在的环境化学物质如何与土壤矿物质成分结合在一起以及不同抗生素之间的竞争如何导致某些药物在土壤中保留某些药物以及将其他药物冲入附近的水中如何键合，这将使我们有一个原子级的了解课程。对于在环境中抗菌素耐药性（AMR）的潜在发展以及下部动物和植物及其转移到食物链中的污染物中，这至关重要。欧盟委员会最近发布了一条通讯，概述了“环境中药品的欧盟战略方法”，迫切要求对环境中药用产品的风险有了改进的了解，特别是指出与“环境有关的知识差距药物的命运和“多种物质”的存在。此外，2022年5月，欧洲兽医联合会在环境中在药品的欧洲生物医学政策论坛上举行了一个欧洲生物医学政策论坛，得出的结论是，高浓度的抗生素，尤其是它们的代谢副产品，构成了紧迫的世界范围内世界生态毒理学威胁。兽医抗生素是最大的药物污染物组之一，是现代农业实践的中流型，因此，它们现在无处不在，在农业土壤中无处不在，直接通过动物排泄物直接出院，并通过使用动物粪便将有机肥料，其后果仍然令人担忧。但是，抗生素不会孤立地发生，并且是化学鸡尾酒的一部分，在该化学鸡尾酒中，与其他物质的相互作用可以改变其行为和风险。因此，了解控制土壤中抗生素的迁移率和行为的竞争性吸附过程的复杂化学反应至关重要。在没有这种理解的情况下，化学可用性与抗生素诱导作用的潜力之间存在很大的知识差距。因此，我们将这一建议重点放在化学环境的不知情发展上，该化学环境可能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表面相互作用的动态途径，从而揭示哪种抗生素或代谢物最强烈与矿物表面键合，以及在存在多分子的情况下这些相互作用发生的情况。因此，目的是建立可用于改善当前环境命运模型的详细化学知识，并对抗生素以及最终其他新出现的污染物和活性药物成分（API）产生更加细微的了解，在土壤中表现出来。这项工作将导致围绕兽医良好实践的政策影响，并将为将环境风险评估带入进入环境，完全最新，与不同的环境方案相关的新药物进行环境风险评估。这项研究与一种“一种健康”方法一致，该方法认识到动物，人类和环境健康的互连，并且通过解决环境污染物，这三种方法都可以积极地增强。这是对第一原理动态建模的雄心勃勃的使用，但是现在与Advent Tier 1、2和3计算资源范围内的建模范围内。