Comparative genomics of enterococci and carbapenem resistant bacteria across a One-health continuum

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Zaidi, Sani-e-Zehra
University of Lethbridge. Faculty of Arts and Science
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Lethbridge, Alta. : University of Lethbridge, Dept. of Chemistry and Biochemistry
Antimicrobial resistance is considered a One Health problem, affecting human, livestock, and environmental health. The overuse of antimicrobials in human and livestock settings exerts selective pressure, resulting in the proliferation of antimicrobial-resistant bacterial strains. Enterococci and Escherichia coli exist ubiquitously in One Health sectors and are therefore used as indicator bacteria in antimicrobial resistance surveillance programs. These bacteria carry antimicrobial resistance genes on mobile genetic elements that may transfer to other bacterial species, most importantly to pathogenic bacteria. In this thesis, we characterized Enterococcus species recovered from One Health sectors and carbapenem-resistant bacteria in Canada. Phenotypic characterization was conducted using the disc diffusion method according to standard CLSI protocols, and whole sequencing using short and long-read platforms was used for genotypic characterization. Additionally, whole-genome comparative genomics was used to investigate the genomic relatedness among isolates from One Health sectors and the effect of antimicrobial usage on antimicrobial resistance in each sector. We identified Enterococcus hirae as the prevalent Enterococcus spp. in bovine and swine production systems, while Enterococcus faecium was predominantly found in poultry. In human clinical isolates, Enterococcus faecium and Enterococcus faecalis were predominantly identified. In antimicrobial resistance profiling of Enterococcus spp., we found that tetracycline (tetL, tetM) and macrolide resistance (ermB) genes exist universally in E. faecium and E. faecalis from all One Health sectors. However, these resistance genes were predominantly found in bovine-sourced E. hirae compared to human settings. Across livestock sectors, the analysis showed that multidrug-resistant E. faecium and E. faecalis isolates were more commonly found in poultry than in swine and bovine cattle. The reconstruction of a core-genome-based phylogenetic tree of E. hirae, E. faecium, and E. faecalis did not reveal segregation based on their sample source. However, in E. faecium, the majority of clinical and municipal wastewater isolates were mapped to the hospital-associated clade. The study on carbapenem-resistant bacteria showed that the prevalence of carbapenem-resistant bacteria in beef production is rare, even after culture enrichment with carbapenem. The majority of carbapenem-resistant species recovered from bovine feedlot samples carried intrinsic resistance genes against carbapenem. Moreover, in the comparative genomic analysis of Pseudomonas aeruginosa, bovine-sourced isolates were phylogenetically different from human clinical isolates.
One-health , enterococci , antimicrobial resistance , comparative genomics , whole genome sequencing , carbapenem resistance , mobile genetic elements