Comparative Genomic Profiles of Salmonella Typhimurium and Salmonella Dublin Bovine Isolates from the U.S. Indicate Possible Factors Associated with the Host Adaptation of Salmonella Dublin in the Region

<i>Salmonella</i> Dublin (<i>S.</i> Dublin) and <i>Salmonella</i> Typhimurium (<i>S.</i> Typhimurium) are commonly linked to bovine salmonellosis. <i>S.</i> Dublin is, however, considered a bovine-adapted serovar for primarily infecting and thriving in cattle. Using <i>S.</i> Typhimurium (a generalist serovar) as a benchmark, this study investigates genomic factors contributing to <i>S.</i> Dublin's adaptation to cattle hosts in the U.S. A total of 1337 <i>S.</i> Dublin and 787 <i>S.</i> Typhimurium whole-genome sequences from bovine sources were analyzed with CARD (version 4.0.0), ARG-NOTT (version 6), and AMRfinderPlus (version 4.0.3) for antimicrobial resistance (AMR) genes; VFDB and AMRfinderPlus for virulence genes; AMRFinderPlus for stress genes; and Plasmidfinder for plasmids. Existing clonal groups among isolates of the two serovars were also investigated using the Hierarchical Clustering of Core Genome Multi-Locus Sequence Typing (HierCC-cgMLST) model. The results revealed minimal genomic variation among <i>S.</i> Dublin isolates. Comparatively, the IncX1 plasmid was somewhat exclusively identified in <i>S.</i> Dublin isolates and each carried an average of four plasmids (<i>p</i>-value < 0.05). Furthermore, <i>S</i>. Dublin isolates exhibited a higher prevalence of AMR genes against key antimicrobials, including aminoglycosides, beta-lactams, tetracyclines, and sulfonamides, commonly used in U.S. cattle production. Additionally, Type VI secretion system genes <i>tssJKLM</i> and <i>hcp2</i>/<i>tssD2</i>, essential for colonization, were found exclusively in <i>S.</i> Dublin isolates with over 50% of these isolates possessing genes that confer resistance to heavy metal stressors, like mercury. These findings suggest that <i>S.</i> Dublin's adaptation to bovine hosts in the U.S. is supported by a conserved genetic makeup enriched with AMR genes, virulence factors, and stress-related genes, enabling it to colonize and persist in the bovine gut.