Resistance to critically important antibiotics beyond humans and farm environments : the genetic epidemiology of resistance from other sources and the relationships between them

Antibiotic resistance (ABR) is a global problem impacting humans, animals, and environmental health, causing great economic loss and threatening food security. Whole genome sequencing (WGS) is a valuable tool when characterizing ABR bacteria from a one-health perspective, however, few studied have investigated evidence for direct sharing between one-health compartments. Studies by the OH-STAR project have used WGS to characterize Escherichia coli resistant to two critically important antibacterials (CIAs); third-generation cephalosporins (3GCs) and fluoroquinolones (FQs) from humans and cattle within a 50 x 50 km study area. Here we investigated 600 dogs in the same study region using WGS and phylogenetic analysis to characterize ABR E. coli in dogs and to identify evidence of sharing between dogs, humans and/or cattle. We also carried out risk factor analysis for excretion of CIA resistant E. coli in dogs. In addition, we characterized CIA resistant E. coli from zoo mammals in the study region. Faecal samples from 600 dogs and 167 samples from zoo mammals were processed to select ABR E. coli which were then subjected to WGS. We found evidence for sharing of CIA resistant E. coli between humans, cattle, and dogs in our study region, and identified "geographical associations", where dogs living in rural areas carried E. coli more similar to cattle than those living in urban areas. Risk factor analysis demonstrated a strong association between feeding raw meat and excretion of 3GC-R and FQ-R E. coli by dogs, confirming farm animal to dog transmission of these bacteria. We also found evidence for farm animal to human transmission of phylogroup A/B1 E. coli, accounting for 11% of human BSI within our study region in 2020, identified due to their carriage of farm animal specific ABR genes. Furthermore, we demonstrated the carriage of nitrofurantoin resistant E. coli by dogs, which may also be due to raw feeding, suggesting an unexpected farm animal reservoir for such E. coli. The zoo environment was a hotspot for evolution and circulation of CIA resistant E. coli, but there was no evidence of escape into the local community. These studies highlight the importance of ABR surveillance from a one-health perspective, which can be beneficial for the control of ABR bacterial prevalence.