Patterns of genome evolution that have accompanied host adaptation inSalmonella

Abstract

Many bacterial pathogens are specialized, infecting one or few hosts, and this is often associated with more acute disease presentation. Specific genomes show markers of this specialization, which often reflect a balance between gene acquisition and functional gene loss. WithinSalmonella entericasubspeciesenterica, a single lineage exists that includes human and animal pathogens adapted to cause infection in different hosts, includingS. entericaserovar Enteritidis (multiple hosts),S.Gallinarum (birds), andS.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. The structure ofS.Enteritidis is more complex than previously known, as a second clade ofS.Enteritidis was revealed that is distinct from those commonly seen to cause disease in humans or animals, and that is more closely related toS.Gallinarum. Isolates from this second clade were tested in a chick model of infection and exhibited a reduced colonization phenotype, which we postulate represents an intermediate stage in pathogen–host adaptation.