engleski

Francisella tularensis travels a twisted road within macrophages

Francisella tularensis is a highly infectious intracellular bacterium that causes fulminating disease and is a potential bioweapon. Although entry of the bacteria into macrophages is mediated by novel asymmetric, spacious pseudopod loops, the nascent phagosome becomes tight fitting within seconds of formation. The modulation of phagosome biogenesis is followed by disruption of the phagosome and bacterial escape into the cytoplasm where they replicate. Here we examined the role of the Francisella pathogenicity island (FPI) proteins IglD and IglC in the intracellular fate of F. tularensis subsp. novicida within human macrophages. We show that F. tularensis iglD and iglC mutant strains are defective for survival and replication within U937 macrophages and human monocyte-derived macrophages (hMDMs). The defect in intracellular replication of both mutants is associated with a defect in disruption of the phagosome and failure to escape into the cytoplasm. We conclude that the proteins iglD and IglC are essential for modulating phagosome biogenesis and subsequent bacterial escape into the cytoplasm. This is the first example of specific virulence factors of F. tularensis that are essential for evasion of fusion of the FCP to lysosomes.

Francisella tularensis; phagosome

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