AUTHOR=Busch Anne , Thomas Prasad , Zuchantke Eric , Brendebach Holger , Neubert Kerstin , Gruetzke Josephine , Al Dahouk Sascha , Peters Martin , Hotzel Helmut , Neubauer Heinrich , Tomaso Herbert 

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

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.00344

DOI=10.3389/fmicb.2018.00344

ISSN=1664-302X

ABSTRACT=<p><italic>Francisella</italic> (<italic>F.</italic>) <italic>tularensis</italic> 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 <italic>F. tularensis</italic> subsp. <italic>holarctica</italic> strain 12T0050 that caused fatal tularemia in a hare. Besides the genomic structure, we focused on the analysis of oriC, unique to the <italic>Francisella</italic> genus and regulating replication in and outside hosts and the first report on genomic DNA methylation of a <italic>Francisella</italic> strain. The high quality genome was used to establish and evaluate a diagnostic whole genome sequencing pipeline. A genotyping strategy for <italic>F. tularensis</italic> was developed using various bioinformatics tools for genotyping. Additionally, whole genome sequences of <italic>F. tularensis</italic> subsp. <italic>holarctica</italic> 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 <italic>F. tularensis</italic> subsp. <italic>holarctica.</italic></p>