An outbreak of respiratory tularemia caused by diverse clones of francisella tularensis

Anders Johansson, Adrian Lärkeryd, Micael Widerström, Sara Mörtberg, Kerstin Myrtännäs, Caroline Öhrman, Dawn Birdsell, Paul S Keim, David M Wagner, Mats Forsman, Pär Larsson

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 nucle-otide 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.

Original languageEnglish (US)
Pages (from-to)1546-1553
Number of pages8
JournalClinical Infectious Diseases
Volume59
Issue number11
DOIs
StatePublished - Dec 1 2014

Fingerprint

Francisella tularensis
Tularemia
Disease Outbreaks
Clone Cells
Genome
Sweden
Single Nucleotide Polymorphism
Biological Warfare Agents
Bacteria
Finland
Inhalation
Cues
Virulence
Nucleotides

Keywords

  • Bacterial infections
  • Epidemiology
  • Francisella tularensis
  • Genomics
  • Tularemia

ASJC Scopus subject areas

  • Infectious Diseases
  • Microbiology (medical)

Cite this

Johansson, A., Lärkeryd, A., Widerström, M., Mörtberg, S., Myrtännäs, K., Öhrman, C., ... Larsson, P. (2014). An outbreak of respiratory tularemia caused by diverse clones of francisella tularensis. Clinical Infectious Diseases, 59(11), 1546-1553. https://doi.org/10.1093/cid/ciu621

An outbreak of respiratory tularemia caused by diverse clones of francisella tularensis. / Johansson, Anders; Lärkeryd, Adrian; Widerström, Micael; Mörtberg, Sara; Myrtännäs, Kerstin; Öhrman, Caroline; Birdsell, Dawn; Keim, Paul S; Wagner, David M; Forsman, Mats; Larsson, Pär.

In: Clinical Infectious Diseases, Vol. 59, No. 11, 01.12.2014, p. 1546-1553.

Research output: Contribution to journalArticle

Johansson, A, Lärkeryd, A, Widerström, M, Mörtberg, S, Myrtännäs, K, Öhrman, C, Birdsell, D, Keim, PS, Wagner, DM, Forsman, M & Larsson, P 2014, 'An outbreak of respiratory tularemia caused by diverse clones of francisella tularensis', Clinical Infectious Diseases, vol. 59, no. 11, pp. 1546-1553. https://doi.org/10.1093/cid/ciu621
Johansson A, Lärkeryd A, Widerström M, Mörtberg S, Myrtännäs K, Öhrman C et al. An outbreak of respiratory tularemia caused by diverse clones of francisella tularensis. Clinical Infectious Diseases. 2014 Dec 1;59(11):1546-1553. https://doi.org/10.1093/cid/ciu621
Johansson, Anders ; Lärkeryd, Adrian ; Widerström, Micael ; Mörtberg, Sara ; Myrtännäs, Kerstin ; Öhrman, Caroline ; Birdsell, Dawn ; Keim, Paul S ; Wagner, David M ; Forsman, Mats ; Larsson, Pär. / An outbreak of respiratory tularemia caused by diverse clones of francisella tularensis. In: Clinical Infectious Diseases. 2014 ; Vol. 59, No. 11. pp. 1546-1553.
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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 nucle-otide 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.",
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AU - Lärkeryd, Adrian

AU - Widerström, Micael

AU - Mörtberg, Sara

AU - Myrtännäs, Kerstin

AU - Öhrman, Caroline

AU - Birdsell, Dawn

AU - Keim, Paul S

AU - Wagner, David M

AU - Forsman, Mats

AU - Larsson, Pär

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N2 - 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 nucle-otide 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.

AB - 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 nucle-otide 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.

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KW - Epidemiology

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KW - Genomics

KW - Tularemia

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