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Front. Microbiol. | doi: 10.3389/fmicb.2018.00344

Revisiting Francisella tularensis subsp. holarctica, causative agent of tularemia in Germany with bioinformatics: New insights in genome structure, DNA methylation and comparative phylogenetic analysis

 Anne Busch1*, Prasad Thomas1,  Eric Zuchantke1,  Holger Brendebach2,  Kerstin Neubert3, Josephine Gruetzke2,  Sascha Al Dahouk2, Martin Peters4,  Helmut Hotzel1,  Heinrich Neubauer1 and Herbert Tomaso1
  • 1IBIZ, Friedrich Loeffler Institut Jena, Germany
  • 2Federal Institute for Risk Assessment, Germany
  • 3Institute of Computer Science, Department of Mathematics and Computer Science, Algorithmic Bioinformatics, Freie Universität Berlin, Germany
  • 4Standort Arnsberg, Chemisches und Veterinäruntersuchungsamt Westfalen, Germany

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 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.

Keywords: Francisella tularensis subsp. holarctica, genome analysis, Tularemia, high quality genome, phylogeny

Received: 05 Dec 2017; Accepted: 12 Feb 2018.

Edited by:

Steve Lindemann, Purdue University, United States

Reviewed by:

Max MAURIN, Université Grenoble Alpes, France
Jean Challacombe, Los Alamos National Laboratory (DOE), United States
Jason Sahl, Northern Arizona University, United States  

Copyright: © 2018 Busch, Thomas, Zuchantke, Brendebach, Neubert, Gruetzke, Al Dahouk, Peters, Hotzel, Neubauer and Tomaso. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Anne Busch, Friedrich Loeffler Institut Jena, IBIZ, Naumburgerstr 96a, Jena, 07745, Thuringia, Germany,