Whole-genome epidemiology links phage-mediated acquisition of a virulence gene to the clonal expansion of a pandemic serovar Typhimurium clone.

Epidemic and pandemic clones of bacterial pathogens with distinct characteristics continually emerge, replacing those previously dominant through mechanisms that remain poorly characterized. Here, whole-genome-sequencing-powered epidemiology linked horizontal transfer of a virulence gene, , to the emergence and clonal expansion of a new epidemic serovar Typhimurium (. Typhimurium) clone. The gene is sporadically distributed within the genus and rare in . Typhimurium lineages, but was acquired multiple times during clonal expansion of the currently dominant pandemic monophasic . Typhimurium sequence type (ST) 34 clone. Ancestral state reconstruction and time-scaled phylogenetic analysis indicated that was not present in the common ancestor of the epidemic clade, but later acquisition resulted in increased clonal expansion of -containing clones that was temporally associated with emergence of the epidemic, consistent with increased fitness. The gene was mainly associated with a temperate bacteriophage mTmV, but recombination with other bacteriophage and apparent horizontal gene transfer of the gene cassette resulted in distribution among at least four mobile genetic elements within the monophasic . Typhimurium ST34 epidemic clade. The mTmV prophage lysogenic transfer to other serovars was limited, but included the common pig-associated . Derby (. Derby). This may explain mTmV in . Derby co-circulating on farms with monophasic . Typhimurium ST34, highlighting the potential for further transfer of the virulence gene in nature. We conclude that whole-genome epidemiology pinpoints potential drivers of evolutionary and epidemiological dynamics during pathogen emergence, and identifies targets for subsequent research in epidemiology and bacterial pathogenesis.