The phylogeographic pattern of Francisella tularensis in Sweden indicates a Scandinavian origin of Eurosiberian tularaemia.

Previous studies of the causative agent of tularaemia, Francisella tularensis have identified phylogeographic patterns suggestive of environmental maintenance reservoirs. To investigate the phylogeography of tularaemia in Sweden, we selected 163 clinical isolates obtained during 1995-2009 in 10 counties and sequenced one isolate's genome to identify new genetic markers. An improved typing scheme based on two indels and nine SNPs was developed using hydrolysis or TaqMan MGB probe assays. The results showed that much of the known global genetic diversity of F. tularensis subsp. holarctica is present in Sweden. Thirteen of the 163 isolates belonged to a new genetic group that is basal to all other known members of the major genetic clade B.I, which is spread across the Eurosiberian region. One hundred and twenty-five of the 163 Swedish isolates belonged to B.I, but individual clades' frequencies differed from county to county (P < 0.001). Subsequent analyses revealed a correlation between genotype variation over time and recurrent outbreaks at specific places, supporting the 'maintenance reservoir' environmental maintenance hypothesis. Most importantly, the findings reveal the presence of diverse source populations of F. tularensis subsp. holarctica in Sweden and suggest a historical spread of the disease from Scandinavia to other parts of Eurosiberia.

[1]  A. Sjöstedt,et al.  Worldwide Genetic Relationships among Francisella tularensis Isolates Determined by Multiple-Locus Variable-Number Tandem Repeat Analysis , 2004, Journal of bacteriology.

[2]  W. Ryan Easterday,et al.  Strain-Specific Single-Nucleotide Polymorphism Assays for the Bacillus anthracis Ames Strain , 2006, Journal of Clinical Microbiology.

[3]  Steven J. M. Jones,et al.  Abyss: a Parallel Assembler for Short Read Sequence Data Material Supplemental Open Access , 2022 .

[4]  N. Perna,et al.  progressiveMauve: Multiple Genome Alignment with Gene Gain, Loss and Rearrangement , 2010, PloS one.

[5]  Mats Forsman,et al.  A Real-Time PCR Array for Hierarchical Identification of Francisella Isolates , 2009, PloS one.

[6]  T. Brettin,et al.  Molecular Evolutionary Consequences of Niche Restriction in Francisella tularensis, a Facultative Intracellular Pathogen , 2009, PLoS pathogens.

[7]  Paul Keim,et al.  Phylogeography of Francisella tularensis subsp. holarctica, Europe , 2012, Emerging infectious diseases.

[8]  A. Johansson,et al.  Identification of Francisella tularensis Cluster in Central and Western Europe , 2009, Emerging infectious diseases.

[9]  Raymond K. Auerbach,et al.  Phylogeography of Francisella tularensis: Global Expansion of a Highly Fit Clone , 2009, Journal of bacteriology.

[10]  P. Keim,et al.  Molecular Epidemiology, Evolution, and Ecology of Francisella , 2007, Annals of the New York Academy of Sciences.

[11]  Erik Bäck,et al.  Landscape Epidemiology of Tularemia Outbreaks in Sweden , 2009, Emerging infectious diseases.

[12]  M. Nei,et al.  MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. , 2011, Molecular biology and evolution.

[13]  S. Telford,et al.  Nonrandom Distribution of Vector Ticks (Dermacentor variabilis) Infected by Francisella tularensis , 2009, PLoS pathogens.

[14]  Paul Keim,et al.  Anthrax molecular epidemiology and forensics: using the appropriate marker for different evolutionary scales. , 2004, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[15]  Inanç Birol,et al.  De novo transcriptome assembly with ABySS , 2009, Bioinform..

[16]  R. Penn Francisella tularensis (Tularemia) , 2010 .

[17]  Amy J. Vogler,et al.  Phylogeography of Francisella tularensis ssp. holarctica in France , 2011, Letters in applied microbiology.

[18]  G. Olin THE OCCURRENCE AND MODE OF TRANSMISSION OF TULAREMIA IN SWEDEN. , 2009 .

[19]  S. Francesconi,et al.  Genomic Deletion Marking an Emerging Subclone of Francisella tularensis subsp. holarctica in France and the Iberian Peninsula , 2007, Applied and Environmental Microbiology.

[20]  Paul Keim,et al.  Phylogeography of Francisella tularensis subspecies holarctica from the country of Georgia , 2011, BMC Microbiology.

[21]  N. D. Levine,et al.  NATURAL NIDALITY OF TRANSMISSIBLE DISEASES , 1966 .

[22]  Steven J. M. Jones,et al.  De novo assembly and analysis of RNA-seq data , 2010, Nature Methods.

[23]  M. Forsman,et al.  Canonical Insertion-Deletion Markers for Rapid DNA Typing of Francisella tularensis , 2007, Emerging infectious diseases.