TY - JOUR AU - Busch, Anne AU - Thomas, Prasad AU - Zuchantke, Eric AU - Brendebach, Holger AU - Neubert, Kerstin AU - Gruetzke, Josephine AU - Al Dahouk, Sascha AU - Peters, Martin AU - Hotzel, Helmut AU - Neubauer, Heinrich AU - Tomaso, Herbert PY - 2018 M3 - Original Research TI - Revisiting Francisella tularensis subsp. holarctica, Causative Agent of Tularemia in Germany With Bioinformatics: New Insights in Genome Structure, DNA Methylation and Comparative Phylogenetic Analysis JO - Frontiers in Microbiology UR - https://www.frontiersin.org/articles/10.3389/fmicb.2018.00344 VL - 9 SN - 1664-302X N2 - 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. ER -