Genomic approach to transmission and compartmentalization of extended-spectrum cephalosporin resistance in Enterobacteriaceae from animals and humans

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Extended-spectrum cephalosporins (ESCs) are antimicrobial drugs which are used to treat serious bacterial infections such as those caused by Enterobacteriaceae, a large family of Gram-negative bacteria that includes many familiar pathogens, including Salmonella, Escherichia coli, Yersinia pestis (the cause of plague), Klebsiella and Shigella (the cause of bacterial dysentery). Resistance to ESCs in Enterobacteriaceae is a major challenge for public health worldwide. The international presence of ESC resistance in almost every ecological niche and biological compartment, including both animals and humans, makes it an ideal target to study the spread of antimicrobial resistance (AMR). This project intends to use high resolution whole genome, transcriptome, and protein data along with evolutionary and experimental approaches to assess the similarities between a variety of ecological niches and biological compartments formed by Enterobacteriaceae species, host species/source (humans, dogs, cattle, swine, chicken, meat products) and geography (Europe: Germany and France, and North America: Canada). These similarities will serve as a basis to identify and focus further on bacterial subtypes and their mobile genetic elements (such as plasmids) able to spread across compartments, using whole genome sequencing. A combination of analytical approaches will allow an assessment of the directionality of transmission between compartments. These analyses will be complemented by series of field experiments on the transmission of ESC resistance plasmids in two animal models (chicken and cattle), and on the effects of ESC resistance plasmids on their bacterial hosts. These experiments will help to identify major transmission pathways between animals and humans and potential new intervention targets for the control of ESC resistance. The team assembled for this project consists of experienced researchers with a wide spectrum of expertise ideal for the successful completion of a study of antimicrobial resistance in the context of One Health.