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Francisella  ( F. )  tularensis  is a highly virulent, Gram-negative bacterial pathogen and the causative agent of the zoonotic disease tularemia. Here, we generated, analyzed and characterized a high quality circular genome sequence of the  F. tularensis  subsp.  holarctica  strain 12T0050 that caused fatal tularemia in a hare. Besides the genomic structure, we focused on the analysis of oriC, unique to the  Francisella  genus and regulating replication in and outside hosts and the first report on genomic DNA methylation of a  Francisella  strain. The high quality genome was used to establish and evaluate a diagnostic whole genome sequencing pipeline. A genotyping strategy for  F. tularensis  was developed using various bioinformatics tools for genotyping. Additionally, whole genome sequences of  F. tularensis  subsp.  holarctica  isolates isolated in the years 2008–2015 in Germany were generated. A phylogenetic analysis allowed to determine the genetic relatedness of these isolates and confirmed the highly conserved nature of  F. tularensis  subsp.  holarctica.

frontiers in microbiology

Revisiting Francisella tularensis subsp. holarctica, Causative Agent of Tularemia in Germany With Bioinformatics: New Insights in Genome Structure, DNA Methylation and Comparative Phylogenetic Analysis