title: Emergence of host-adaptedSalmonellaEnteritidis through rapid evolution in an immunocompromised host.
abstract: Host adaptation is a key factor contributing to the emergence of new bacterial, viral and parasitic pathogens. Many pathogens are considered promiscuous because they cause disease across a range of host species, while others are host-adapted, infecting particular hosts1. Host adaptation can potentially progress to host restriction where the pathogen is strictly limited to a single host species and is frequently associated with more severe symptoms. Host-adapted and host-restricted bacterial clades evolve from within a broader host-promiscuous species and sometimes target different niches within their specialist hosts, such as adapting from a mucosal to a systemic lifestyle. Genome degradation, marked by gene inactivation and deletion, is a key feature of host adaptation, although the triggers initiating genome degradation are not well understood. Here, we show that a chronic systemic non-typhoidalSalmonellainfection in an immunocompromised human patient resulted in genome degradation targeting genes that are expendable for a systemic lifestyle. We present a genome-based investigation of a recurrent blood-borneSalmonella entericaserotype Enteritidis (S. Enteritidis) infection covering 15 years in an interleukin (IL)-12 β-1 receptor-deficient individual that developed into an asymptomatic chronic infection. The infectingS.Enteritidis harbored a mutation in the mismatch repair genemutSthat accelerated the genomic mutation rate. Phylogenetic analysis and phenotyping of multiple patient isolates provides evidence for a remarkable level of within-host evolution that parallels genome changes present in successful host-restricted bacterial pathogens but never before observed on this timescale. Our analysis identifies common pathways of host adaptation and demonstrates the role that immunocompromised individuals can play in this process.
authors.affiliation: The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Klemm
authors.affiliation: Department of Infectious Diseases, Cambridge University Hospitals, Cambridge, United Kingdom.|Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.
authors.forename: Effrossyni
authors.initials: E
authors.lastname: Gkrania-Klotsas
authors.affiliation: The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Hadfield
authors.affiliation: The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Forbester
authors.affiliation: The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Harris
authors.affiliation: The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Christine
authors.initials: C
authors.lastname: Hale
authors.affiliation: School of Immunity and Infection, College of Medicine and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Heath
authors.affiliation: The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wileman
authors.affiliation: The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Clare
authors.affiliation: The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Leanne
authors.initials: L
authors.lastname: Kane
authors.affiliation: The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Goulding
authors.affiliation: The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Otto
authors.affiliation: The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Sally
authors.initials: S
authors.lastname: Kay
authors.affiliation: Department of Clinical Biochemistry and Immunology, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Rainer
authors.initials: R
authors.lastname: Doffinger
authors.affiliation: Clinical Microbiology and Public Health Laboratory, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: Cooke
authors.affiliation: Department of Infectious Diseases, Cambridge University Hospitals, Cambridge, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Carmichael
authors.affiliation: Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Andrew Ml
authors.initials: AM
authors.lastname: Lever
authors.affiliation: The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.|School of Immunity and Infection, College of Medicine and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Calman A
authors.initials: CA
authors.lastname: MacLennan
authors.affiliation: Department of Clinical Biochemistry and Immunology, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Dinakantha
authors.initials: D
authors.lastname: Kumararatne
authors.affiliation: The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.|Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.affiliation: The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.|The Institute of Food Research, Colney, Norwich, United Kingdom.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kingsley
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000328:Adult; D016470:Bacteremia / Q000382:microbiology; D002908:Chronic Disease; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D058507:Host Specificity; D054884:Host-Pathogen Interactions; D006801:Humans; D016867:Immunocompromised Host; D007153:Immunologic Deficiency Syndromes / Q000150:complications*; D053711:Interleukin-12 Receptor beta 1 Subunit / Q000172:deficiency / Q000235:genetics; D009154:Mutation; D059645:Mutation Rate; D012480:Salmonella Infections / Q000150:complications / Q000382:microbiology*; D012477:Salmonella enteritidis / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D014774:Virulence
chemical_list: D053711:Interleukin-12 Receptor beta 1 Subunit