Molecular-Genetic Bases of Differences between Tularaemia Pathogen Subspecies and Francisella tularensis subsp. holarctica Strain Typing

Abstract—A comparison of the genomic sequences of F. tularensis subsp. tularensis, holarctica, and mediasiatica, subspecies of tularaemia pathogen virulent for human and animals, revealed a high (up to 99.26–99.8%) homology between their genomes. Every year, a new improved whole-genome phylogeny is suggested, in particular, for F. tularensis subsp. holarctica, a subspecies that shows low genetic diversity and is widely distributed worldwide. This limited genetic variation observed in F. tularensis subsp. holarctica genomes makes sequencing, along with tandem repeat number analysis (TRNA) and identification of single nucleotide substitutions (SNPs) and insertions and deletion (InDels), a preferable genetic tool for molecular typing of strains within the subspecies. The current F. tularensis subsp. holarctica strain genotyping pipeline separates four major phylogenetic groups (B.4, B.6, B.12, and B.16) and more than 300 individual genotypic populations within this subspecies, which differ by several specific single nucleotide substitutions and deletions.