Canada_IPAP Constructing model microbiomes to study microbial interactions and AMR in dairy production systems

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The World Health Organization considers antimicrobial resistance (AMR) as an urgent global threat to health, livelihood, economies, and environment and a threat to the progress of Sustainable Development Goals. In 2019, 1.27 million deaths were attributed to AMR and this number is predicted to rise to 10 million by 2050 without effective intervention. Antibiotics are routinely used in veterinary medicine for therapeutic and prophylactic purposes, and during routine animal husbandry in many countries. Antibiotics and their metabolites persist in the gastrointestinal tract of animals, and their accumulation at sub-lethal concentrations in the gut induces a selective pressure on the microbiota that facilitates the maintenance of antibiotic-resistant bacteria (ARB) and enrichment of antibiotic resistance genes (ARGs). Food-producing farm animals are prone to pathogen infections and antibiotic treatment, and potentially transmit AMR pathogens to each other, the associated environment, and humans, raising risks to public health.Consequently, a substantial fraction of antibiotic residues (up to 90%) and their associated ARGs are shed in manure. Animal manure is often spread on land as fertiliser without proper treatment, posing risks of disseminating ARBs and ARGs - with/between indigenous soil populations through horizontal gene transfer (HGT). In the UK, the annual amount of manure used in agriculture is pegged at over 70 million tonnes. Many studies have demonstrated ARB and ARG increases in soil microbiome induced by manure fertilising, which becomes a hotspot for HGT. From the environment, ARGs may be cycled back to animals through fodder ingestion, direct contact, airborne particles, and runoff to water, the latter three routes also become threats to humans, in addition to the food chain transmission. Effective mitigation strategies are required to reduce AMR levels in the One Health cycle.This project will combine the expertise from UK and Canada to investigate, in complex microbiomes in dairy cattle and associated environments, how AMR can be affected/controlled by microbial ecological interactions. Field samples from organic and conventional dairy farms in UK and Canada will be analysed and compared on microbiome and AMR. Collective results using shotgun metagenomics tools and high-throughput multiplexed amplicon sequencing and ddPCR methods will generate an overview and detailed information on AMR burden in dairy farms. The project aims to construct isolation libraries and synthetic microbial communities (which improves reproducibility and replications) to create model microbiomes for mechanistic investigations of ecological interactions and AMR. This project will contribute to the long-term goal of AMR transmission mitigation.