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Exploring the molecular epidemiology of blaCTX-M mediated resistance among Enterobacterales from Canadian domestic animals

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Title: Exploring the molecular epidemiology of blaCTX-M mediated resistance among Enterobacterales from Canadian domestic animals
Author: Cormier, Ashley
Department: Department of Pathobiology
Program: Pathobiology
Advisor: Boerlin, Patrick
Abstract: Historically, extended spectrum cephalosporin (ESC) resistance among Enterobacterales in Canada has been attributed to the blaSHV and blaCMY gene families. However, this pattern is beginning to change with the emergence of the blaCTX-M among bacteria since the early 2000’s. It has been demonstrated that food animals can act as a reservoir for ESC resistance. Since the microbiota of humans, animals and the environment are interconnected, it’s important that practices are implemented to limit the production of resistance. Understanding how mobile genetic elements carrying these resistance determinants influence bacterial persistence could be an important factor in informing these practices. Therefore, the objectives of this thesis were twofold. First being to identify and evaluate major reservoirs of ESC resistance among Canadian domestic animals and assess their similarities with regards to their associated resistance determinants. Second, to evaluate how blaCTX-M and its associated mobile genetic elements behave in comparison to commonly recovered ESC resistance genes circulating in Canada (i.e., blaCMY-2). To meet these objectives, we used short-and long-read genome sequencing to characterize blaCTXM-carrying Escherichia coli isolates and plasmids from Canadian domestic animals (i.e., poultry, swine, cattle, horses, and dogs). In vivo experiments were then performed to assess the impact of widespread IncI1/ST3/CTX-M-1 and IncI1/ST12/CMY-2 plasmids on the persistence of Salmonella Heidelberg in chickens. Not unlike what has been reported globally, the most widely recovered blaCTX-M variants from Canadian domestic animals included blaCTX-M-1,14,15 -27 and -55. The spectrum and prevalence of these variants differed between animal species and is likely related to the number and types of transmission routes feeding into the farm. Along with the identification of conserved plasmids (i.e., IncI1/ST3 and IncHI1/ST2) circulating within and between animal species, clonal spread of some E. coli STs was also apparent. Thus, highlighting the important role that both horizontal gene transfer and clonal spread play in the transmission of blaCTX-M. In vivo experiments showed that IncI1/ST3/CTX-M-1 aids in persistence over time in comparison to IncI1/ST12/CMY-2, however neither plasmid provided a significant fitness advantage. Further work is necessary to identify the factors contributing to the success of IncI1/ST3/CTX-M-1 (e.g., enhanced gut colonization and conjugation assisted persistence).
Date: 2022-03-17
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Related Publications: Cormier, A.C., Chalmers, G., Zamudio, R., Mulvey, M.R., Mather, A.E., and Boerlin, P. Diversity of blaCTX-M-1-carrying plasmids recovered from Escherichia coli isolated from Canadian domestic animals. PLOS ONE. DOI: 10.1371/journal.pone.0264439.Cormier, A.C., Chalmers, G., McAllister, T.A., Cook, S.R., Zaheer, R., Booker, C., Read, R., Hannon, J.S., Gow, S., and Boerlin, P. The presence and diversity of blaCTX-M among Escherichia coli from urban wastewater and feedlot cattle, in Alberta, Canada. Microbial Drug Resistance. DOI: 10.1089/mdr.2019.0112.Cormier, A.C., Zhang, P.L.C., Chalmers, G., Weese, J.S., Deckert, A., Mulvey, M., McAllister, T. A., and Boerlin, P. Diversity of CTX-M- positive Escherichia coli recovered from animals in Canada. Veterinary Microbiology. DOI: 10.1016/j.vetmic.2019.02.031.

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