Chromosome Rearrangement and Diversification of Francisella tularensis Revealed by the Type B (OSU18) Genome Sequence

Abstract

The ␥-proteobacterium Francisella tularensis is one of the most infectious human pathogens, and the highly virulent organism F. tularensis subsp. tularensis (type A) and less virulent organism F. tularensis subsp. holarctica (type B) are most commonly associated with significant disease in humans and animals. Here we report the complete genome sequence and annotation for a low-passage type B strain (OSU18) isolated from a dead beaver found near Red Rock, Okla., in 1978. A comparison of the F. tularensis subsp. holarctica sequence with that of F. tularensis subsp. tularensis strain Schu4 (P. Larsson et al., Nat. Genet. 37:153-159, 2005) highlighted genetic differences that may underlie different pathogenicity phenotypes and the evolutionary relationship between type A and type B strains. Despite extensive DNA sequence identity, the most significant difference between type A and type B isolates is the striking amount of genomic rearrangement that exists between the strains. All but two rearrangements can be attributed to homologous recombination occurring between two prominent insertion elements, ISFtu1 and ISFtu2. Numerous pseudogenes have been found in the genomes and are likely contributors to the difference in virulence between the strains. In contrast, no rearrangements have been observed between the OSU18 genome and the genome of the type B live vaccine strain (LVS), and only 448 polymorphisms have been found within non-transposase-coding sequences whose homologs are intact in OSU18. Nonconservative differences between the two strains likely include the LVS attenuating mutation(s).

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.…”

Development of novel plasmid vectors and a promoter trap system in Francisella tularensis compatible with the pFLN10 based plasmids

“…Further larger studies identifying more promoters will be required to delineate an intracellular activated promoter consensus sequence and we plan on extending these studies to establish a regulatory network within F. tularensis. The availability of multiple F. tularensis genomes (Larsson et al, 2005;Petrosino et al, 2006) and the genomes of close relatives will allow further studies of these processes to identify potential mechanisms of intervention in these regulatory pathways leading to potential therapies.…”