Nucl Acids Res 2005, 33:244–248.CrossRef 55. Sali A, Potterton L, Yuan F, Van Vlijmen H, Karplus M: Evaluation of comparative

protein modeling by MODELLER. Proteins 1995,23(3):318–326.PubMedCrossRef Authors’ contributions All authors reviewed and approved the final version Emricasan purchase of the manuscript. LR and PG conducted the protein analysis. YZ performed bioinformatics analyses. DMD supervised the work in USA. PG, BM and AR designed the study, obtained funding and wrote the manuscript. Competing interests The authors declare that they have no competing interests.”
“Background Francisella tularensis is a highly clonal, recently-emerged pathogen that causes tularemia, which presents in several main forms: pneumonic (30%-60% mortality), ulceroglandular, and oropharyngeal [1]. The latter two are associated with lower mortality. F. tularensis is currently divided into three subspecies (tularensis, holarctica and mediasiatica), with F. novicida recognized as a very closely related species, or as

another subspecies by some authors [2–4]. These taxa vary in virulence, geographic distribution, overall genetic diversity, and host/vector associations [3, 5–9]. Human tularemia is a disease at which the clinical severity depends upon the route of infection, subspecies of the infection strain, and timely therapeutic response [9]. Cases in Europe are caused by F. tularensis subsp. Selleck Brigatinib holarctica, and in many rural areas of the Balkans and countries further east outbreaks are water-borne, resulting in oropharyngeal tularemia [10–12]. No known cases by F. tularensis subsp. mediasiatica are known and only a few by F. novicida have been documented [13, 14]. F. tularensis subsp. tularensis is restricted to North

Rebamipide America, whereas F. tularensis subsp. holarctica is found throughout the Northern Hemisphere [3, 15]. Despite its wider geographic distribution F. tularensis subsp. holarctica has markedly lower genetic diversity than F. tularensis subsp. tularensis [5, 7, 8]. Significant gains toward deciphering the evolutionary history of F. tularensis overall and, in particular, F. tularensis subsp. holarctica have been made by using whole genome comparisons for single nucleotide polymorphism (SNP) discovery coupled with subsequent canonical SNP (canSNP) analysis [15, 16]. Numerous new groups were identified within F. tularensis subsp. holarctica (Figure 1A) [15, 16], two of which, B.Br.013 (includes subclades B.Br.013/014 and B.Br.LVS in [15]) and B.Br.FTNF002-00, were predominant in Europe but geographically segregated [15]. In the Western European countries of Spain, France, and Switzerland selleckchem almost all isolates belong to the highly monomorphic B.Br.FTNF002-00 group [15–18]. In contrast, in large portions of Central and Eastern Europe, from the Czech Republic to Russia, most F. tularensis subsp. holarctica isolates are assigned to various lineages within the B.Br.013 group [15, 16]. Figure 1 Phylogenies of Francisella tularensis subsp. holarctica.