Molecular Evolutionary Consequences of Niche Restriction in Francisella tularensis, a Facultative Intracellular Pathogen

Abstract

Francisella tularensis is a potent mammalian pathogen well adapted to intracellular habitats, whereas F. novicida and F. philomiragia are less virulent in mammals and appear to have less specialized lifecycles. We explored adaptations within the genus that may be linked to increased host association, as follows. First, we determined the genome sequence of F. tularensis subsp. mediasiatica, the only subspecies that had not been previously sequenced. This genome, and those of 12 other F. tularensis isolates, were then compared to the genomes of F. novicida (three isolates) and F. philomiragia (one isolate). Signs of homologous recombination were found in ∼19.2% of F. novicida and F. philomiragia genes, but none among F. tularensis genomes. In addition, random insertions of insertion sequence elements appear to have provided raw materials for secondary adaptive mutations in F. tularensis, e.g. for duplication of the Francisella Pathogenicity Island and multiplication of a putative glycosyl transferase gene. Further, the five major genetic branches of F. tularensis seem to have converged along independent routes towards a common gene set via independent losses of gene functions. Our observations suggest that despite an average nucleotide identity of >97%, F. tularensis and F. novicida have evolved as two distinct population lineages, the former characterized by clonal structure with weak purifying selection, the latter by more frequent recombination and strong purifying selection. F. tularensis and F. novicida could be considered the same bacterial species, given their high similarity, but based on the evolutionary analyses described in this work we propose retaining separate species names.

Genomic analyses of Francisella tularensis strains confirm disease transmission from drinking water sources, Turkey, 2008, 2009 and 2012

“…Because F. tularensis exhibits very little genetic variability, high-resolution analytical methods such as whole genome sequencing are appropriate for genetic typing in epidemiological investigations of tularaemia outbreaks and for source-tracing [29,30]. Initial canSNP analysis of the six included isolates revealed that they all belonged to the F. tularensis genetic clade B.12, which dominates in Europe between Scandinavia and the Black Sea [7,8,[23][24][25].…”

Francisella tularensis Molecular Typing Using Differential Insertion Sequence Amplification

“…Despite the subtype A.I and A.II strains having similar numbers of IS elements (6,20), there is considerable overall variation in chromosome architectures (18,23). The current study revealed that a 312-bp insertion or deletion derived from ISFtu1 was responsible for the size heterogeneity within the CR-derived amplicons in the subtype A.I and A.II strains but that discrimination between these two clades was still apparent.…”

“…mediasiatica, whereas classification of the fourth subspecies, F. tularensis subsp. novicida, remains in contention (13,14,20). Differentiation among these subspecies is important due to their variation in virulence and for the tracking of tularemia outbreaks.…”

Degeneration of a CRISPR/Cas system and its regulatory target during the evolution of a pathogen

“…[16][17][18] F. holarctica and F. tularensis species contain 41 genes not present in F. novicida, that are predicted to play important roles during infection of mammals. 18 While the function of the majority of these unique genes has not been determined, six are predicted to play roles in the biosynthesis of O-antigen, a critical surface structure necessary for pathogenesis.…”