title: An outbreak of respiratory tularemia caused by diverse clones of Francisella tularensis.
abstract: BACKGROUND
  The bacterium Francisella tularensis is recognized for its virulence, infectivity, genetic homogeneity, and potential as a bioterrorism agent. Outbreaks of respiratory tularemia, caused by inhalation of this bacterium, are poorly understood. Such outbreaks are exceedingly rare, and F. tularensis is seldom recovered from clinical specimens.
  
  
  METHODS
  A localized outbreak of tularemia in Sweden was investigated. Sixty-seven humans contracted laboratory-verified respiratory tularemia. F. tularensis subspecies holarctica was isolated from the blood or pleural fluid of 10 individuals from July to September 2010. Using whole-genome sequencing and analysis of single-nucleotide polymorphisms (SNPs), outbreak isolates were compared with 110 archived global isolates.
  
  
  RESULTS
  There were 757 SNPs among the genomes of the 10 outbreak isolates and the 25 most closely related archival isolates (all from Sweden/Finland). Whole genomes of outbreak isolates were >99.9% similar at the nucleotide level and clustered into 3 distinct genetic clades. Unexpectedly, high-sequence similarity grouped some outbreak and archival isolates that originated from patients from different geographic regions and up to 10 years apart. Outbreak and archival genomes frequently differed by only 1-3 of 1 585 229 examined nucleotides.
  
  
  CONCLUSIONS
  The outbreak was caused by diverse clones of F. tularensis that occurred concomitantly, were widespread, and apparently persisted in the environment. Multiple independent acquisitions of F. tularensis from the environment over a short time period suggest that natural outbreaks of respiratory tularemia are triggered by environmental cues. The findings additionally caution against interpreting genome sequence identity for this pathogen as proof of a direct epidemiological link.
authors.affiliation: Department of Clinical Microbiology, Clinical Bacteriology, and Laboratory for Molecular Infection Medicine Sweden, Umeå University.
authors.forename: Anders
authors.initials: A
authors.lastname: Johansson
authors.affiliation: CBRN Defence and Security, Swedish Defence Research Agency, Umeå
authors.forename: Adrian
authors.initials: A
authors.lastname: Lärkeryd
authors.affiliation: Department of Clinical Microbiology, Clinical Bacteriology, Umeå University.
authors.forename: Micael
authors.initials: M
authors.lastname: Widerström
authors.affiliation: Department of Infectious Diseases, Östersund County Hospital, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Mörtberg
authors.affiliation: CBRN Defence and Security, Swedish Defence Research Agency, Umeå
authors.forename: Kerstin
authors.initials: K
authors.lastname: Myrtännäs
authors.affiliation: CBRN Defence and Security, Swedish Defence Research Agency, Umeå
authors.forename: Caroline
authors.initials: C
authors.lastname: Ohrman
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff.
authors.forename: Dawn
authors.initials: D
authors.lastname: Birdsell
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff.
authors.forename: Paul
authors.initials: P
authors.lastname: Keim
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff.
authors.forename: David M
authors.initials: DM
authors.lastname: Wagner
authors.affiliation: CBRN Defence and Security, Swedish Defence Research Agency, Umeå
authors.forename: Mats
authors.initials: M
authors.lastname: Forsman
authors.affiliation: CBRN Defence and Security, Swedish Defence Research Agency, Umeå
authors.forename: Pär
authors.initials: P
authors.lastname: Larsson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004269:DNA, Bacterial / Q000235:genetics; D004196:Disease Outbreaks; D005260:Female; D005604:Francisella tularensis / Q000145:classification / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D012141:Respiratory Tract Infections / Q000453:epidemiology* / Q000382:microbiology*; D013548:Sweden / Q000453:epidemiology; D014406:Tularemia / Q000453:epidemiology* / Q000382:microbiology*; D055815:Young Adult
chemical_list: D004269:DNA, Bacterial
keywords: Francisella tularensis; bacterial infections; epidemiology; genomics; tularemia
references.citation: Euro Surveill. 2006;11(2):58-60
references.pmid: 16525197
references.citation: Clin Infect Dis. 2012 Nov 15;55(10):1283-90
references.pmid: 22911645
references.citation: Lancet Infect Dis. 2013 Feb;13(2):137-46
references.pmid: 23158499
references.citation: Emerg Infect Dis. 2010 Feb;16(2):238-43
references.pmid: 20113553
references.citation: Scand J Infect Dis. 1985;17(4):371-5
references.pmid: 4089543
references.citation: PLoS One. 2010 Jun 25;5(6):e11147
references.pmid: 20593022
references.citation: N Engl J Med. 1979 Oct 11;301(15):826-8
references.pmid: 481515
references.citation: Mol Biol Evol. 2011 Oct;28(10):2731-9
references.pmid: 21546353
references.citation: Nature. 2011 Aug 24;477(7365):462-5
references.pmid: 21866102
references.citation: JAMA. 2001 Jun 6;285(21):2763-73
references.pmid: 11386933
references.citation: J Bacteriol. 2009 Apr;191(8):2474-84
references.pmid: 19251856
references.citation: Emerg Infect Dis. 2009 Dec;15(12):1937-47
references.pmid: 19961673
references.citation: Environ Microbiol. 2013 Feb;15(2):634-45
references.pmid: 23253075
references.citation: mBio. 2011 Sep 01;2(4):e00157-11
references.pmid: 21862630
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):299-304
references.pmid: 17182744
references.citation: Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):3065-70
references.pmid: 22315421
references.citation: Scand J Infect Dis. 1971;3(1):7-16
references.pmid: 5099427
references.citation: Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):577-82
references.pmid: 23271803
references.citation: PLoS Pathog. 2009 Jun;5(6):e1000472
references.pmid: 19521508
references.citation: Emerg Infect Dis. 2008 Dec;14(12):1928-30
references.pmid: 19046524
references.citation: BMJ Open. 2013 Jan 09;3(1):
references.pmid: 23306006
references.citation: Euro Surveill. 2008 Aug 07;13(32):
references.pmid: 18761900
references.citation: Ann N Y Acad Sci. 2007 Jun;1105:30-66
references.pmid: 17435120
references.citation: Clin Infect Dis. 2011 Nov;53(10):e133-41
references.pmid: 22002987
references.citation: N Engl J Med. 2012 Jun 14;366(24):2267-75
references.pmid: 22693998
references.citation: Appl Environ Microbiol. 2013 Feb;79(4):1134-9
references.pmid: 23220959
references.citation: Genome Res. 2009 Jun;19(6):1117-23
references.pmid: 19251739
references.citation: Sci Transl Med. 2012 Aug 22;4(148):148ra116
references.pmid: 22914622
references.citation: N Engl J Med. 2001 Nov 29;345(22):1601-6
references.pmid: 11757506
references.citation: N Engl J Med. 2013 Sep 26;369(13):1195-205
references.pmid: 24066741
references.citation: Science. 2011 Jan 28;331(6016):430-4
references.pmid: 21273480
references.citation: Science. 2010 Jan 22;327(5964):469-74
references.pmid: 20093474
references.citation: PLoS Pathog. 2012;8(11):e1003008
references.pmid: 23209404