Cell biology and molecular ecology of Francisella tularensis

Authors

  • Marina Santic,

    1. Department of Microbiology and Parasitology, Medical Faculty, Brace Branchetta 20, University of Rijeka, 51000 Rijeka, Croatia.
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  • Souhaila Al-Khodor,

    1. Department of Microbiology and Immunology, University of Louisville College of Medicine, 319 Abraham Flexner Way 55A, Louisville, KY 40202, USA.
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  • Yousef Abu Kwaik

    Corresponding author
    1. Department of Microbiology and Immunology, University of Louisville College of Medicine, 319 Abraham Flexner Way 55A, Louisville, KY 40202, USA.
      *E-mail abukwaik@louisville.edu; Tel. (+1) 502 852 4117; Fax (+1) 502-852-7531.
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*E-mail abukwaik@louisville.edu; Tel. (+1) 502 852 4117; Fax (+1) 502-852-7531.

Summary

Francisella tularensis is a highly infectious intracellular bacterium that causes the fulminating disease tularemia, which can be transmitted between mammals by arthorpod 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-β 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.

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