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

在这个试点项目中，我们将探索两种常用的兽用抗生素（恩诺沙星和氟苯尼考）的化学，以及它们的代谢产物，在主要的土壤矿物（高岭石和针铁矿）的表面，使用第一原理计算模型。这将使我们对这些无处不在的环境化学物质如何与土壤的矿物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以及其他药物被冲洗到附近的水道中有一个原子级的理解。这对于环境中抗菌素耐药性（AMR）的潜在发展以及低等动物和植物对污染物的直接吸收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报，概述了“欧盟环境中药品战略方法”，紧急呼吁加强对药品在环境中的风险的了解，并特别指出与“药品的环境命运”和“多种物质”的存在有关的知识差距。此外，2022年5月，欧洲兽医联合会举办了一个关于环境中药物的欧洲生物医学政策论坛，得出的结论是，高浓度的抗生素，特别是其代谢副产物，构成了紧迫的全球生态毒理学威胁。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，它们现在普遍存在于农业土壤中，通过动物排泄物和使用动物粪便作为有机肥料直接排放到土地上，其后果仍然令人担忧。然而，抗生素并不是孤立存在的，它是化学鸡尾酒的一部分，与其他物质的相互作用可以改变它们的行为和风险。因此，了解控制抗生素在土壤中的流动性和行为的竞争性吸附过程的复杂化学是至关重要的。如果不了解这一点，在化学品的可用性和抗生素诱导效应的可能性之间存在着重大的知识差距。因此，我们将这一建议集中在化学环境的无意发展上，这种化学环境可以在下游导致有害的微生物进化。我们将使用第一性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，揭示哪些抗生素或代谢物与矿物表面的结合最强，以及在多个分子存在下这些相互作用会发生什么。因此，其目的是建立详细的化学知识，可用于改善当前的环境归宿模型，并对抗生素以及最终其他新兴污染物和活性药物成分（API）在土壤中的行为进行更细致的了解。这项工作将对兽医良好做法的政策产生影响，并将推动对进入环境的新药进行环境风险评估，使其完全更新并与不同的环境情景相关。该研究与“一个健康”的方法是一致的，该方法认识到动物，人类和环境健康的相互联系，通过解决环境污染物，这三者都可以得到积极的改善。这是一个雄心勃勃的使用第一原理动态建模，但现在是在范围内的到来层1，2和3计算资源。

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.