Patterns of Genome Evolution That Have Accompanied Host Adaptation in Salmonella Dublin. Salmonella enterica subsp. enterica serovar Dublin strain:SC50

Many bacterial pathogens are specialised, infecting only one, or a few, hosts, and this is often associated with more acute disease presentation. By looking at specific genomes we can see markers of this specialisation, which often reflect a balance between gene acquisition and functional gene loss. Within Salmonella enterica subspecies enterica, a single lineage exists that includes human and animal pathogens adapted to cause infection in different hosts, including S. enterica serovar Enteritidis (multiple hosts), S. Gallinarum (birds) and S. Dublin (cattle). This provides an excellent evolutionary context in which differences between these pathogen genomes can be related to host range. Genome sequences were obtained from ~60 isolates selected to represent the known diversity of this lineage. Examination and comparison of the clades within the phylogeny of this lineage revealed signs of host restriction as well as evolutionary events that mark a path to host generalism. We have identified the nature and order of events for both evolutionary trajectories. The impact of functional gene loss was predicted based upon position within metabolic pathways and confirmed with phenotyping assays. In the host adapted clades, loss of particular traits such as tetrathionate reduction and adenosylcobalamin biosynthesis could be related to their role in host infection. The structure of S. Enteritidis is more complex than previously known, as a second clade of S. Enteritidis was revealed that is distinct from those commonly seen to cause disease in humans or animals, and which are more closely related to S. Gallinarum. Isolates from this novel clade were tested in a chick model of infection, and exhibited a reduced colonisation phenotype, which we postulate represents an intermediate stage in pathogen-host adaptation.