title: Seeding and Establishment of Legionella pneumophila in Hospitals: Implications for Genomic Investigations of Nosocomial Legionnaires' Disease.
abstract: Legionnaires' disease is an important cause of hospital-acquired pneumonia and is caused by infection with the bacterium Legionella. Because current typing methods often fail to resolve the infection source in possible nosocomial cases, we aimed to determine whether whole-genome sequencing (WGS) could be used to support or refute suspected links between cases and hospitals. We focused on cases involving a major nosocomial-associated strain, L. pneumophila sequence type (ST) 1.
  
  
  
  WGS data from 229 L. pneumophila ST1 isolates were analyzed, including 99 isolates from the water systems of 17 hospitals and 42 clinical isolates from patients with confirmed or suspected hospital-acquired infections, as well as isolates obtained from or associated with community-acquired sources of Legionnaires' disease.
  
  
  
  Phylogenetic analysis demonstrated that all hospitals from which multiple isolates were obtained have been colonized by 1 or more distinct ST1 populations. However, deep sampling of 1 hospital also revealed the existence of substantial diversity and ward-specific microevolution within the population. Across all hospitals, suspected links with cases were supported with WGS, although the degree of support was dependent on the depth of environmental sampling and available contextual information. Finally, phylogeographic analysis revealed that hospitals have been seeded with L. pneumophila via both local and international spread of ST1.
  
  
  
  WGS can be used to support or refute suspected links between hospitals and Legionnaires' disease cases. However, deep hospital sampling is frequently required due to the potential coexistence of multiple populations, existence of substantial diversity, and similarity of hospital isolates to local populations.
authors.affiliation: Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge, UK.|Respiratory and Vaccine Preventable Bacteria Reference Unit, Public Health England, London, UK.
authors.forename: Sophia
authors.initials: S
authors.lastname: David
authors.affiliation: Respiratory and Vaccine Preventable Bacteria Reference Unit, Public Health England, London, UK.|European Programme for Public Health Microbiology Training, European Centre for Disease Prevention and Control, Stockholm, Sweden.
authors.forename: Baharak
authors.initials: B
authors.lastname: Afshar
authors.affiliation: Respiratory and Vaccine Preventable Bacteria Reference Unit, Public Health England, London, UK.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mentasti
authors.affiliation: French National Reference Center of Legionella, Hospices Civils de Lyon, France.|International Center of Infectiology Research, INSERM, U1111, CNRS, UMR5308, Université Lyon 1, École Normale Supérieure de Lyon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Ginevra
authors.affiliation: Microbiology, Assistance publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Podglajen
authors.affiliation: Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge, UK.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Harris
authors.affiliation: Respiratory and Vaccine Preventable Bacteria Reference Unit, Public Health England, London, UK.
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Chalker
authors.affiliation: French National Reference Center of Legionella, Hospices Civils de Lyon, France.|International Center of Infectiology Research, INSERM, U1111, CNRS, UMR5308, Université Lyon 1, École Normale Supérieure de Lyon, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Jarraud
authors.affiliation: Respiratory and Vaccine Preventable Bacteria Reference Unit, Public Health England, London, UK.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Harrison
authors.affiliation: Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
mesh_terms: D019295:Computational Biology / Q000379:methods; D003428:Cross Infection / Q000453:epidemiology* / Q000382:microbiology; D023281:Genomics / Q000379:methods*; D005838:Genotype; D006761:Hospitals; D006801:Humans; D016952:Legionella pneumophila / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D007877:Legionnaires' Disease / Q000453:epidemiology* / Q000382:microbiology; D017720:Molecular Epidemiology / Q000379:methods*; D058889:Molecular Typing / Q000379:methods*; D010802:Phylogeny; D017422:Sequence Analysis, DNA / Q000379:methods; D014871:Water Microbiology
keywords: Legionella pneumophila; Legionnaires’ disease; bacterial genomics; whole-genome sequencing; nosocomial infections