Francisella tularensis is a highly infectious intracellular bacterium that 
causes the fulminating disease tularemia, which can be transmitted between 
mammals by arthropod vectors. Genomic studies have shown that the F. tularensis 
has been undergoing genomic decay with the most virulent strains having the 
lowest number of functional genes. Entry of F. tularensis into macrophages is 
mediated by looping phagocytosis and is associated with signalling through Syk 
tyrosine kinase. Within macrophages and arthropod-derived cells, the 
Francisella-containing phagosome matures transiently into an acidified late 
endosome-like phagosome with limited fusion to lysosomes followed by rapid 
bacterial escape into the cytosol within 30-60 min, and bacterial proliferation 
within the cytosol. The Francisella pathogenicity island, which potentially 
encodes a putative type VI secretion system, is essential for phagosome 
biogenesis and bacterial escape into the cytosol within macrophages and 
arthropod-derived cells. Initial sensing of F. tularensis in the cytosol 
triggers IRF-3-dependent IFN-beta secretion, type I IFNR-dependent signalling, 
activation of the inflammasome mediated by caspase-1, and a pro-inflammatory 
response, which is suppressed by triggering of SHIP. The past few years have 
witnessed a quantum leap in our understanding of various aspects of this 
organism and this review will discuss these remarkable advances.