Genomic Diversity, Virulence, and Antimicrobial Resistance of Strains from Cows and Humans.

is a leading cause of severe infections in humans and dairy cows, and these infections are rapidly becoming untreatable due to the emergence of multidrug-resistant (MDR) strains. However, little is known about the relationship between bovine and human isolates at the genome population level. Here, we investigated the genomic structures, pangenomic profiles, virulence determinants, and resistomes of 308  isolates from humans and dairy cows, including 96 newly sequenced cow isolates. We identified 177 functional protein families that were significantly different across human and bovine isolates; genes expressing proteins related to metal ion (iron, zinc, and calcium) metabolism were significantly more prevalent among the bovine isolates. Siderophore systems were found to be prevalent in both the bovine and the human isolates. In addition, we found that the ferric uptake operon was significantly more prevalent in clinical mastitis cases than in healthy cows. Furthermore, on two dairy farms, we identified a unique IncN-type plasmid, pC5, coharboring and (A) genes, which confer resistance to cephalosporins and macrolides, respectively. We provide here the complete annotated sequence of this plasmid. We demonstrate here the genetic diversity of isolates from dairy cows and the mixed phylogenetic lineages between bovine and human isolates. The ferric uptake operon genes were more prevalent in strains from clinical mastitis cows. Furthermore, we report the emergence of an IncN-type plasmid carrying the and (A) genes among dairy farms in the United States. Our study evaluated the genomic diversity of the bovine and human isolates, and the findings uncovered different profiles of virulence determinants among bovine and human isolates at the genome population level.