The impact of Host restriction of Escherichia coli on Transmission dynamics and spread of antimicrobial Resistance

The prevalence of antimicrobial resistance (AMR) is increasing rapidly worldwide, including inbacteria colonizing healthy human and animal populations. The recent reports of plasmidmediated colistin resistance, potentially associated with colistin usage in agriculture, furtherraise fears of infections that have become untreatable due to AMR. The commensal flora ofhumans and animals is a reservoir of AMR encoding genes and Escherichia coli in particularcan carry multiple AMR determinants. Antimicrobial resistance transmission within E. coliappears dominated by certain lineages. To what extent these are restricted to certain hostspecies is unknown. Such host restriction may be an important determinant of the likelihoodof transmission of resistant E. coli between different reservoirs, such as between animal andhuman hosts. The identification of determinants that allow disentanglement of the differentmodes of resistance transmission (i.e. bacteria vs mobile genetic elements such as plasmids)is crucial for a more targeted design of interventions to prevent and reduce transmission ofresistance. The proposed research aims to identify determinants of host restriction of E. coliand their potential association with antimicrobial resistance transmission and prevalence. Wepropose a One Health approach using mixed methods, including whole genome sequencingof a large collection of E. coli isolates from human, animal and environmental sources indifferent geographic areas across Europe and in Vietnam, experimental models to study therole of host restriction determinants in transmission and bacterial fitness, and mathematicalmodelling. The research should result in a risk-assessment, estimating the contribution ofdifferent transmission routes and predicting the effect of interventions on a single route on theoverall prevalence in the different compartments.