title: Citrobacter rodentium is an unstable pathogen showing evidence of significant genomic flux.
abstract: Citrobacter rodentium is a natural mouse pathogen that causes attaching and effacing (A/E) lesions. It shares a common virulence strategy with the clinically significant human A/E pathogens enteropathogenic E. coli (EPEC) and enterohaemorrhagic E. coli (EHEC) and is widely used to model this route of pathogenesis. We previously reported the complete genome sequence of C. rodentium ICC168, where we found that the genome displayed many characteristics of a newly evolved pathogen. In this study, through PFGE, sequencing of isolates showing variation, whole genome transcriptome analysis and examination of the mobile genetic elements, we found that, consistent with our previous hypothesis, the genome of C. rodentium is unstable as a result of repeat-mediated, large-scale genome recombination and because of active transposition of mobile genetic elements such as the prophages. We sequenced an additional C. rodentium strain, EX-33, to reveal that the reference strain ICC168 is representative of the species and that most of the inactivating mutations were common to both isolates and likely to have occurred early on in the evolution of this pathogen. We draw parallels with the evolution of other bacterial pathogens and conclude that C. rodentium is a recently evolved pathogen that may have emerged alongside the development of inbred mice as a model for human disease.
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Nicola K
authors.initials: NK
authors.lastname: Petty
authors.forename: Theresa
authors.initials: T
authors.lastname: Feltwell
authors.forename: Derek
authors.initials: D
authors.lastname: Pickard
authors.forename: Simon
authors.initials: S
authors.lastname: Clare
authors.forename: Ana L
authors.initials: AL
authors.lastname: Toribio
authors.forename: Maria
authors.initials: M
authors.lastname: Fookes
authors.forename: Kevin
authors.initials: K
authors.lastname: Roberts
authors.forename: Rita
authors.initials: R
authors.lastname: Monson
authors.forename: Satheesh
authors.initials: S
authors.lastname: Nair
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kingsley
authors.forename: Richard
authors.initials: R
authors.lastname: Bulgin
authors.forename: Siouxsie
authors.initials: S
authors.lastname: Wiles
authors.forename: David
authors.initials: D
authors.lastname: Goulding
authors.forename: Thomas
authors.initials: T
authors.lastname: Keane
authors.forename: Craig
authors.initials: C
authors.lastname: Corton
authors.forename: Nicola
authors.initials: N
authors.lastname: Lennard
authors.forename: David
authors.initials: D
authors.lastname: Harris
authors.forename: David
authors.initials: D
authors.lastname: Willey
authors.forename: Richard
authors.initials: R
authors.lastname: Rance
authors.forename: Lu
authors.initials: L
authors.lastname: Yu
authors.forename: Jyoti S
authors.initials: JS
authors.lastname: Choudhary
authors.forename: Carol
authors.initials: C
authors.lastname: Churcher
authors.forename: Michael A
authors.initials: MA
authors.lastname: Quail
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.forename: Gad
authors.initials: G
authors.lastname: Frankel
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.forename: George P C
authors.initials: GP
authors.lastname: Salmond
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Thomson
mesh_terms: D000818:Animals; D044082:Citrobacter rodentium / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity*; D004269:DNA, Bacterial / Q000235:genetics; D004195:Disease Models, Animal; D016521:Electrophoresis, Gel, Pulsed-Field; D004756:Enterobacteriaceae Infections / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015321:Gene Rearrangement; D016680:Genome, Bacterial; D042822:Genomic Instability; D006801:Humans; D020071:Interspersed Repetitive Sequences; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000235:genetics; D039002:Prophages / Q000235:genetics; D017422:Sequence Analysis, DNA; D014774:Virulence
chemical_list: D004269:DNA, Bacterial