MEtaGenome-informed Antimicrobial resistance Surveillance: Harnessing long-read sequencing for an analytical, indicator and risk assessment framework

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Antimicrobial resistance (AMR) is a threat to humans, animals, and crops, and requires a coordinated One Health approach. AMR affects many of the goals of the WHO 2030 Agenda for Sustainable Development. Levels of AMR are generally quantified by culturing indicator organisms like E. coli, and determining its resistance. Looking at only one indicator organism in all human, animal, food and environmental samples is like studying ocean life by looking at a single droplet of seawater with a microscope. Interesting differences can be found between droplets but is it really the entire picture?Metagenomic sequencing is a technique that allows identification and quantification of AMR genes and species in a sample without culturing. Currently the use of short read sequencing is more common but limited when AMR quantification is required. One can only quantify genes, not where they are. On a chromosome? Or in a transmittable plasmid or transposon, which can easily spread to pathogens?We propose to use long-read Nanopore sequencing to develop a 'one stop shop' surveillance method. Long reads contain both resistance genes and flanking sequences, thereby identifying the original organism or mobile genetic element, the location, but also genes associated with high transmission risk. We propose integrating into traditional methods to expand surveillance into non-model-organisms.By working with stakeholders in government, industry and academia, this project will support translation of long-read metagenome data into actionable surveillance information for the reduction of risk to human health.