Grant: Team Grant: Joint Programming Initiative on Antimicrobial Resistance (JPIAMR)

Extended-spectrum cephalosporins (ESC) are classified by the World Health Organization as critical for the treatment of infections in humans. Enterobacteriaceae are bacteria normally found in the intestine of healthy individuals, but they can cause numerous infections in humans and animals (some deadly). Resistance to ESC in Enterobacteriaceae is a major challenge for public health worldwide. Its presence in almost every ecological niche and biological compartment and still ongoing expansion make it an ideal target to study the spread of antimicrobial resistance. This project will use genomic, evolutionary, proteomics and experimental approaches to assess the similarities between ecological niches and biological compartments formed by Enterobacteriaceae species, host species/source (humans, dogs, cattle, swine, chicken, meat products) and geography (Germany, France and Canada). These similarities will serve a basis to identify and focus further on bacterial lineages and mobile genetic elements able to spread across compartments. Using genome sequencing and a combination of evolutionary and epidemiologic methods, this project will assess the direction of ESC resistance transmission between ecological niches and compartments. This will be complemented by series of experiments on persistence and transmission of ESC resistance between bacteria in chicken and cattle. The effects of ESC resistance acquisition on other bacterial functions will also be studied by examining the global expression of proteins and RNA other than those directly related to ESC resistance. 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 from four different countries, with a wide spectrum of expertise ideal for the successful completion of a study of antimicrobial resistance in the context of One Health.