Whole-Genome Sequencing of Drug-Resistant Salmonella enterica Isolates from Dairy Cattle and Humans in New York and Washington States Reveals Source and Geographic Associations.

Multidrug-resistant (MDR) can be spread from cattle to humans through direct contact with animals shedding as well as through the food chain, making MDR a serious threat to human health. The objective of this study was to use whole-genome sequencing to compare antimicrobial-resistant (AMR) serovars Typhimurium, Newport, and Dublin isolated from dairy cattle and humans in Washington State and New York State at the genotypic and phenotypic levels. A total of 90 isolates were selected for the study (37 Typhimurium, 32 Newport, and 21 Dublin isolates). All isolates were tested for phenotypic antibiotic resistance to 12 drugs using Kirby-Bauer disk diffusion. AMR genes were detected in the assembled genome of each isolate using nucleotide BLAST and ARG-ANNOT. Genotypic prediction of phenotypic resistance resulted in a mean sensitivity of 97.2 and specificity of 85.2. Sulfamethoxazole-trimethoprim resistance was observed only in human isolates ( < 0.05), while resistance to quinolones and fluoroquinolones was observed only in 6 Typhimurium isolates from humans in Washington State. Newport isolates showed a high degree of AMR profile similarity, regardless of source. Dublin isolates from New York State differed from those from Washington State based on the presence/absence of plasmid replicons, as well as phenotypic AMR susceptibility/nonsusceptibility ( < 0.05). The results of this study suggest that distinct factors may contribute to the emergence and dispersal of AMR in humans and farm animals in different regions. The use of antibiotics in food-producing animals has been hypothesized to select for AMR and associated AMR determinants, which can be transferred to humans through different routes. Previous studies have sought to assess the degree to which AMR livestock- and human-associated strains overlap, as well as the spatial distribution of 's associated AMR determinants, but have often been limited by the degree of resolution at which isolates can be compared. Here, a comparative genomics study of livestock- and human-associated strains from different regions of the United States shows that while many AMR genes and phenotypes were confined to human isolates, overlaps between the resistomes of bovine and human-associated isolates were observed on numerous occasions, particularly for Newport. We have also shown that whole-genome sequencing can be used to reliably predict phenotypic resistance across isolated from bovine sources.