Genetic Relationships of Third-Generation Cephem Resistant Escherichia coli in Humans, Dogs and Cattle using a Novel Clonotyping Assay

Antimicrobial resistance is a global One Health threat connecting antimicrobial use in human health, animal husbandry, and companion animal health with concern for persistence in environmental reservoirs. Complicating this threat is the gap that exists in our understanding of the intersection of antimicrobial resistance among humans and our companion and food production animals. This study applies a visual and statistical approach to further understand antimicrobial resistance characteristics and relatedness of Escherichia coli found in humans, dogs and cattle. The primary study collection included third-generation cephem resistant (3GCR) E. coli isolates recovered from human, dog, and cattle gastrointestinal specimens and secondarily human and dog isolates recovered from infection sources, primarily urinary tract infections. We previously reported on the transferable gene targets encoding for 3GCR in colonizing isolates and here further identified the familial-like clonal group of each resistant isolate using a novel clonotype diagnostic (septatyping). Together, this approach identified distinct genetic signatures among these 3GCR isolates, many of which are peculiar to their respective host species. We found that the overlap measured by the correlation in abundance of shared clonotypes of resistant E. coli among hosts revealed statistically greater similarity between dogs and humans than between cattle and humans. Yet, the reservoir of AMR genes was highest in cattle and secondarily dogs. While these findings demonstrate that clonotypes of 3GCR E. coli in humans, dogs and cattle display significant host specificity, transient colonization from a host enriched with resistant strains may still pose considerable risk of horizontal transfer of resistance genes between hosts living in proximity to each other.