Comparison of Francisella tularensis genomes reveals evolutionary events associated with the emergence of human pathogenic strains

Abstract

Pathogenicity in Francisella tularensis subspecies <p>.Sequencing of the non-pathogenic <it>Francisella tularensis </it>sub-species novicida U112, and comparison with two pathogenic sub-species, provides insights into the evolution of pathogenicity in these species.</p> Abstract Background: Francisella tularensis subspecies tularensis and holarctica are pathogenic to humans, whereas the two other subspecies, novicida and mediasiatica, rarely cause disease. To uncover the factors that allow subspecies tularensis and holarctica to be pathogenic to humans, we compared their genome sequences with the genome sequence of Francisella tularensis subspecies novicida U112, which is nonpathogenic to humans.

Enhanced survival but not amplification of Francisella spp. in the presence of free-living amoebae

“…The larger average size of Ap cells could account for the lower CFU titres of LVS at day 10 and of Schu4 and NY98 at day 7 in the presence of Ap cells, if amoeba size is indicative of bacterialfeeding potential (Figures 1 and 3). Moreover, genomic analysis of LVS, Schu4, and Fn revealed: (1) repeated genomic rearrangements in LVS and Schu4, but not in Fn; (2) absence of 40+ genes in the Fn genome that is present in LVS and Schu4; and (3) presence of approximately 10 genes and pseudogenes unique to Schu4 that presumably confers greater virulence observed with tularensis strains compared with the holarctica strains [41] indicating genetic variations between Ft and Fn may also have contributed to the differences in uptake by each FLA observed in this study.…”

Paralogous Outer Membrane Proteins Mediate Uptake of Different Forms of Iron and Synergistically Govern Virulence in Francisella tularensis tularensis

“…Sixteen F. tularensis and eight F. novicida genomes have been analyzed at PATRIC. Although the pathogenic tularensis strains have accumulated a number of gene inactivation events that are considered to be unimportant to the evolutionary niche that they occupy, they have retained an intact set of iron acquisition related genes found in all naturally occurring Francisella strains this far (50,51). These include the fur repressor and fsl operon, the fupA locus, and the feoB gene encoding the ferrous iron transporter.…”

An intracellularly inducible gene involved in virulence and polyphosphate production in Francisella

“…novicida were generated containing a deletion encompassing the majority of the FTN1472/FTT1564 ORF, replacing it with a chloramphenicol-resistance cassette. Examination of the genome sequence data for strains SCHU S4 (Larsson et al, 2005) and U112 (Rohmer et al, 2007) indicated that the FTT1564 gene was not part of an operon (Fig. 3) and that the observed phenotypes would therefore be unlikely to be due to polar effects on downstream genes.…”