title: Gene flow in environmental Legionella pneumophila leads to genetic and pathogenic heterogeneity within a Legionnaires' disease outbreak.
abstract: BACKGROUND
  Legionnaires' disease is a severe form of pneumonia caused by the environmental bacterium Legionella pneumophila. Outbreaks commonly affect people with known risk factors, but the genetic and pathogenic complexity of L. pneumophila within an outbreak is not well understood. Here, we investigate the etiology of the major Legionnaires' disease outbreak that occurred in Edinburgh, UK, in 2012, by examining the evolutionary history, genome content, and virulence of L. pneumophila clinical isolates.
  
  
  RESULTS
  Our high resolution genomic approach reveals that the outbreak was caused by multiple genetic subtypes of L. pneumophila, the majority of which had diversified from a single progenitor through mutation, recombination, and horizontal gene transfer within an environmental reservoir prior to release. In addition, we discover that some patients were infected with multiple L. pneumophila subtypes, a finding which can affect the certainty of source attribution. Importantly, variation in the complement of type IV secretion systems encoded by different genetic subtypes correlates with virulence in a Galleria mellonella model of infection, revealing variation in pathogenic potential among the outbreak source population of L. pneumophila.
  
  
  CONCLUSIONS
  Taken together, our study indicates previously cryptic levels of pathogen heterogeneity within a Legionnaires' disease outbreak, a discovery that impacts on source attribution for future outbreak investigations. Furthermore, our data suggest that in addition to host immune status, pathogen diversity may be an important influence on the clinical outcome of individual outbreak infections.
authors.forename: Paul R
authors.initials: PR
authors.lastname: McAdam
authors.forename: Charles W
authors.initials: CW
authors.lastname: Vander Broek
authors.forename: Diane S J
authors.initials: DS
authors.lastname: Lindsay
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Ward
authors.forename: Mary F
authors.initials: MF
authors.lastname: Hanson
authors.forename: Michael
authors.initials: M
authors.lastname: Gillies
authors.forename: Mick
authors.initials: M
authors.lastname: Watson
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Stevens
authors.forename: Giles F
authors.initials: GF
authors.lastname: Edwards
authors.forename: J Ross
authors.initials: JR
authors.lastname: Fitzgerald
mesh_terms: D004196:Disease Outbreaks; D051456:Gene Flow; D016680:Genome, Bacterial; D059014:High-Throughput Nucleotide Sequencing; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D016952:Legionella pneumophila / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D007877:Legionnaires' Disease / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D010802:Phylogeny