Geography Shapes the Population Genomics ofSalmonella entericaDublin

ABSTRACT Salmonella enterica serotype Dublin ( S. Dublin) is a bovine-adapted serotype that can cause serious systemic infections in humans. Despite the increasing prevalence of human infections and the negative impact on agricultural processes, little is known about the population structure of the serotype. To this end, we compiled a manually curated dataset comprising of 880 S. Dublin genomes. Core genome phylogeny and ancestral state reconstruction revealed that region-specific clades dominate the global population structure of S. Dublin. Strains of S. Dublin in the UK are genomically distinct from US, Brazilian and African strains. The geographical partitioning impacts the composition of the core genome as well as the ancillary genome. Antibiotic resistance genes are almost exclusively found in US genomes and is mediated by an IncA/C2 plasmid. Phage content and the S. Dublin virulence plasmid were strongly conserved in the serotype. Comparison of S. Dublin to a closely related serotype, Salmonella enterica serotype Enteritidis, revealed that S. Dublin contains 82 serotype specific genes that are not found in S. Enteritidis . Said genes encode metabolic functions involved in the uptake and catabolism of carbohydrates and virulence genes associated with type VI secretion systems and fimbria assembly respectively. IMPORTANCE S. Dublin is a bovine-adapted strain that can also cause human infections. Typical S. Dublin human infections are characterized by invasion of tissue that ultimately traverses to the bloodstream causing life-threatening systemic cases. The preferred course of treatment for such infection is the administration of antibiotics. Thus, it is important to study the population structure of the serotype to monitor and identify which strains present the greatest threats to public health. Consequently, in this work, it was found that S. Dublin genomic features are greatly influenced by the region in which they populate. Our analysis found that most S. Dublin isolates from the US are distinct and have gained multidrug resistance through a new hybrid plasmid. Thus, it would be expected that infections in the US would respond less favorably to the first line of therapy and the region acts as the major source of a multidrug-resistant S. Dublin.