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

Abstract

Multidrug-resistant (MDR) <i>Salmonella enterica</i> can be spread from cattle to humans through direct contact with animals shedding <i>Salmonella</i> as well as through the food chain, making MDR <i>Salmonella</i> a serious threat to human health. The objective of this study was to use whole-genome sequencing to compare antimicrobial-resistant (AMR) <i>Salmonella enterica</i> 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 <i>S</i> Typhimurium, 32 <i>S</i> Newport, and 21 <i>S</i> 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 (<i>P</i> < 0.05), while resistance to quinolones and fluoroquinolones was observed only in 6 <i>S</i> Typhimurium isolates from humans in Washington State. <i>S</i> Newport isolates showed a high degree of AMR profile similarity, regardless of source. <i>S</i> 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 (<i>P</i> < 0.05). The results of this study suggest that distinct factors may contribute to the emergence and dispersal of AMR <i>S. enterica</i> in humans and farm animals in different regions.<b>IMPORTANCE</b> The use of antibiotics in food-producing animals has been hypothesized to select for AMR <i>Salmonella enterica</i> 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 <i>Salmonella</i> strains overlap, as well as the spatial distribution of <i>Salmonella</i>'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 <i>Salmonella</i> 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 <i>Salmonella</i> isolates were observed on numerous occasions, particularly for <i>S</i> Newport. We have also shown that whole-genome sequencing can be used to reliably predict phenotypic resistance across <i>Salmonella</i> isolated from bovine sources.