Genome divergence and increased virulence of outbreak associated Salmonella enterica subspecies enterica serovar Heidelberg

serotype is primarily a poultry adapted serotype of Salmonella that can also colonize other hosts and cause human disease. In this study, we compared the genomes of outbreak associated non-outbreak causing ser. strains from diverse hosts and geographical regions. Human outbreak associated strains in this study were from a 2015 multistate outbreak of ser. involving 15 states in the United States which originated from bull calves. Our clinicopathologic examination revealed that cases involving ser. strains were predominantly young, less than weeks-old, dairy calves. Pre-existing or concurrent disease was found in the majority of the calves. Detection of ser. correlated with markedly increased death losses clinically comparable to those seen in herds infected with Dublin, a known serious pathogen of cattle. Whole genome based single nucleotide polymorphism based analysis revealed that these calf isolates formed a distinct cluster along with outbreak associated human isolates. The defining feature of the outbreak associated strains, when compared to older isolates of . , is that all isolates in this cluster contained fimbrial genes which are generally absent in . . The acquisition of several single nucleotide polymorphisms and the gain of fimbrial genes may have contributed to the increased disease severity of these ser. strains.