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

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The occurrence of antimicrobial resistance (AMR) is rapidly increasing worldwide, including in bacteria found in healthy human and animal populations. The recent reports of colistin resistance, potentially associated with colistin usage in agriculture, further raise fears of infections that have become untreatable due to AMR. The commensal flora of humans and animals is a reservoir of AMR genes and Escherichia coli which is part of the healthy micro-flora can carry multiple AMR determinants. Antimicrobial resistance transmission within E. coli appears to be dominated by certain genetic types of the organism. However, to what extent these are restricted to certain host species (animals/humans etc.) is unknown. Such host restriction may be an important determinant of the likelihood of transmission of resistant E. coli between different reservoirs, such as between animal and human hosts. The identification of genes that allow disentanglement of the different modes of AMR transmission is crucial for a more targeted design of controls to prevent and reduce transmission of AMR. The proposed research aims to identify genes of host restriction of E. coli and their potential association with AMR transmission and occurrence. We propose to utilise whole genome sequencing of a large collection of E. coli isolates from human, animal and environmental sources in different geographic areas across Europe and in Vietnam, experimental models to study the role of host restriction determinants in transmission and bacterial fitness, and mathematical modelling. The research aims to produce a risk-assessment, estimating the contribution of different transmission routes and predicting the effect of controls on AMR. The consortium is uniquely placed to perform this research as it consists of experts in the field of microbiology and antimicrobial resistance, who work in human and animal health domains, and represent highly complementary disciplines.