Complete Genome Sequence of Francisella tularensis Subspecies holarctica FTNF002-00

Abstract

Francisella tularensis subspecies holarctica FTNF002-00 strain was originally obtained from the first known clinical case of bacteremic F. tularensis pneumonia in Southern Europe isolated from an immunocompetent individual. The FTNF002-00 complete genome contains the RD23 deletion and represents a type strain for a clonal population from the first epidemic tularemia outbreak in Spain between 1997–1998. Here, we present the complete sequence analysis of the FTNF002-00 genome. The complete genome sequence of FTNF002-00 revealed several large as well as small genomic differences with respect to two other published complete genome sequences of F. tularensis subsp. holarctica strains, LVS and OSU18. The FTNF002-00 genome shares >99.9% sequence similarity with LVS and OSU18, and is also ∼5 MB smaller by comparison. The overall organization of the FTNF002-00 genome is remarkably identical to those of LVS and OSU18, except for a single 3.9 kb inversion in FTNF002-00. Twelve regions of difference ranging from 0.1–1.5 kb and forty-two small insertions and deletions were identified in a comparative analysis of FTNF002-00, LVS, and OSU18 genomes. Two small deletions appear to inactivate two genes in FTNF002-00 causing them to become pseudogenes; the intact genes encode a protein of unknown function and a drug:H+ antiporter. In addition, we identified ninety-nine proteins in FTNF002-00 containing amino acid mutations compared to LVS and OSU18. Several non-conserved amino acid replacements were identified, one of which occurs in the virulence-associated intracellular growth locus subunit D protein. Many of these changes in FTNF002-00 are likely the consequence of direct selection that increases the fitness of this subsp. holarctica clone within its endemic population. Our complete genome sequence analyses lay the foundation for experimental testing of these possibilities.

Common Ancestry and Novel Genetic Traits of Francisella novicida-Like Isolates from North America and Australia as Revealed by Comparative Genomic Analyses

“…Genomic library construction, sequencing, and finishing were performed at the Genome Science Facilities of Los Alamos National Laboratory, Los Alamos, New Mexico, as described previously (4,6,98). The prediction of the number of subsystems and pairwise BLAST comparisons of protein sets within strains Fx1 and 3523 were performed using Rapid Annotation using Subsystems Technology (RAST), which is a fully automated, prokaryotic genome annotation service (3).…”

Phylogeographical pattern of Francisella tularensis in a nationwide outbreak of tularaemia in Norway, 2011

“…In addition to the 18 Norwegian and 29 selected Swedish strains, six common reference genomes were included (OR96246, FTNF002-00 [26], LVS, Tul7 [13], FSC200 [24], OSU18 [27], and the tree was rooted in FSC022 [28]. The phylogenetic tree was constructed in MEGA6 [29].…”

First indication for a functional CRISPR/Cas system in Francisella tularensis

“…The genome sequences of strain U112, the clinical isolate 3523 (Australian strain) and Fx1 (Texas strain) are available, as well as some Ft. tularensis and F. philomiragia strains (Barabote et al, 2009;Beckstrom-Sternberg et al, 2007;Champion et al, 2009;Chaudhuri et 3 al., 2007;Larsson et al, 2005;Modise et al, 2012;Nalbantoglu et al, 2010;Petrosino et al, 2006;Rohmer et al, 2007;Siddaramappa et al, 2011;Sjodin et al, 2012;Zeytun et al, 2012). Ft. tularensis is a highly infectious zoonotic agent.…”