Phylogeography of Francisella tularensis : Global Expansion of a Highly Fit Clone

Abstract

Francisella tularensis contains several highly pathogenic subspecies, including Francisella tularensis subsp. holarctica, whose distribution is circumpolar in the northern hemisphere. The phylogeography of these subspecies and their subclades was examined using whole-genome single nucleotide polymorphism (SNP) analysis, high-density microarray SNP genotyping, and real-time-PCR-based canonical SNP (canSNP) assays. Almost 30,000 SNPs were identified among 13 whole genomes for phylogenetic analysis. We selected 1,655 SNPs to genotype 95 isolates on a high-density microarray platform. Finally, 23 clade-and subclade-specific canSNPs were identified and used to genotype 496 isolates to establish global geographic genetic patterns. We confirm previous findings concerning the four subspecies and two Francisella tularensis subsp. tularensis subpopulations and identify additional structure within these groups. We identify 11 subclades within F. tularensis subsp. holarctica, including a new, genetically distinct subclade that appears intermediate between Japanese F. tularensis subsp. holarctica isolates and the common F. tularensis subsp. holarctica isolates associated with the radiation event (the B radiation) wherein this subspecies spread throughout the northern hemisphere. Phylogenetic analyses suggest a North American origin for this B-radiation clade and multiple dispersal events between North America and Eurasia. These findings indicate a complex transmission history for F. tularensis subsp. holarctica.

Phylogeographical pattern of Francisella tularensis in a nationwide outbreak of tularaemia in Norway, 2011

“…holarctica strains [8]. High-resolution molecular methods including whole genome sequencing distinguish four major genetic clades denoted B.12, B.6, B.4 and B.16 [9][10][11]. The clades occur with different frequency in different geographical areas [12][13][14][15].…”

Ecological Niche Modeling of Francisella tularensis Subspecies and Clades in the United States

“…First, type B strains were modeled only at the subspecies level, because PFGE does not provide discrimination of type B strains to a finer level. Because genetic substructuring into subpopulations among type B strains has been shown recently using SNPs and multilocus variable number of tandem repeat analyses, 18 ecological-niche models based on these clades will be important for future studies. Second, because of intercorrelations among environmental factors, we cannot ascribe differences among genotypes definitively to any particular environmental dimension; therefore, correlated dimensions exist that could confound associations-this confounding, of course, reflects the complexity of environmental landscapes.…”

Complement sensitivity and factor H binding of European Francisella tularensis ssp. holarctica strains in selected animal species

“…Wild strains were isolated from natural infections of European brown hares and cultured on modified Francis agar (chocolate agar plate supplemented with 0.1% cysteine and 1% glucose). The genetic analysis of the strains was performed on the basis of RD23 (the region of genomic differences 23) deletion and single nucleotide polymorphism (SNP) typing as described before (Dempsey et al, 2007;Vogler et al, 2009). Based on their genetic characteristics the strains from Italy and Spain belong to the group B.FTNF002-00, while the strain from Hungary and LVS cluster in group B.13.…”

“…is dominant, while the B.13 group is most common in northern, central and eastern Europe (Austria, Czech Republic, Finland, Germany, Hungary, Romania, Russia, Slovakia, Sweden, Switzerland, Ukraine) (Vogler et al, 2009;Gyuranecz et al, 2012a;Antwerpen et al, 2013;Maraha et al, 2013;Ariza-Miguel et al, 2014;Origgi et al, 2014).…”