title: Patterns of genome evolution that have accompanied host adaptation in Salmonella.
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. 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. 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 that is more closely related to S. 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.
authors.affiliation: Pathogen Genomics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom; gb4@sanger.ac.uk.
authors.forename: Gemma C
authors.initials: GC
authors.lastname: Langridge
authors.affiliation: Pathogen Genomics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom;
authors.forename: Maria
authors.initials: M
authors.lastname: Fookes
authors.affiliation: Pathogen Genomics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom;
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Connor
authors.affiliation: Pathogen Genomics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom;
authors.forename: Theresa
authors.initials: T
authors.lastname: Feltwell
authors.affiliation: Pathogen Genomics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom;
authors.forename: Nicholas
authors.initials: N
authors.lastname: Feasey
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool L69 7BE, United Kingdom; Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, United Kingdom;
authors.forename: Bryony N
authors.initials: BN
authors.lastname: Parsons
authors.affiliation: Pathogen Genomics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom;
authors.forename: Helena M B
authors.initials: HM
authors.lastname: Seth-Smith
authors.affiliation: Pathogen Genomics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom;
authors.forename: Lars
authors.initials: L
authors.lastname: Barquist
authors.affiliation: Pathogen Genomics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom;
authors.forename: Anna
authors.initials: A
authors.lastname: Stedman
authors.affiliation: College of Medicine, Swansea University, Swansea SA2 8PP, United Kingdom;
authors.forename: Tom
authors.initials: T
authors.lastname: Humphrey
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool L69 7BE, United Kingdom; School of Veterinary Science, University of Liverpool, Liverpool L69 3GB, United Kingdom;
authors.forename: Paul
authors.initials: P
authors.lastname: Wigley
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom;
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Peters
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom;
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Maskell
authors.affiliation: Department of Mathematics and Statistics, University of Helsinki, FI-00014 Helsinki, Finland;
authors.forename: Jukka
authors.initials: J
authors.lastname: Corander
authors.affiliation: Departamento de Desarrollo Biotecnológico, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Montevideo, CP 11600, Uruguay; and.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Chabalgoity
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Nottingham LE12 5RD, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Barrow
authors.affiliation: Pathogen Genomics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom;
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: Pathogen Genomics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom;
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.affiliation: Pathogen Genomics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom;
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Thomson
mesh_terms: D000222:Adaptation, Physiological; D002876:Chromosomes, Bacterial; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D011544:Pseudogenes; D012475:Salmonella / Q000235:genetics*
keywords: Salmonella; host adaptation; metabolism; pseudogene