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

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.