Molecular epidemiology of antimicrobial resistance plasmids in bacteria from animals

点击翻译按钮获取中文摘要

This proposal is part of our extended efforts to understand better the epidemiology of antimicrobial resistance (AMR) in bacteria from animals using molecular methods. The unique approach proposed is to focus on a geographically limited region (Ontario), but to look simultaneously at a broader group of bacteria (i.e. not only E. coli and Salmonella, but Enterobacteriaceae in general) than has traditionally been examined in the past. Based on results from more focused studies, the hypotheses I want to test are that AMR determinants do not flow equally from one ecological compartment to another, resulting in compartmentalization 1) at the bacterial species level, 2) at the animal host species level, and 3) at the commensal/pathogen levels. My fourth hypothesis is that the latter phenomenon can be partially explained by the linkage of AMR and virulence determinants on mobile genetic elements (plasmids) and that these linkages stabilize AMR determinants, thus partially explaining the higher prevalence of AMR in pathogens. To test these hypotheses, I will concentrate efforts on resistance to cephalosporins and fluoroquinolones, and compare the distribution of resistance determinants to these clinically critically important antimicrobials in commensals and pathogens from four farm and companion animal species. The distribution of these determinants among bacterial species, animal species, and commensal/pathogens will allow to test the compartmentalization hypothesis and to identify the main commonalities and bottlenecks in the diffusion of AMR determinants. The observed distribution will allow to select representative commensals and pathogens and to sequence their genomes in order to understand precisely the associations/linkages between AMR genes and between AMR and virulence determinants in the population under study. Finally, to test the last hypothesis, in vivo experiments will be conducted to assess the persistence of resistance and pathogens with linked and non-linked AMR and virulence determinants using wild type and genetically engineered E. coli strains. The expected results of this study will provide new and broader insights into AMR epidemiology at the complex interface of bacterial species, host species, and reservoir-pathogen interactions than has been provided by the past uncoordinated studies on AMR in bacterial from animals. The proposed work will form the basis for the training of one MSc, one PhD, and at least five undergraduate students.