engleski

Modulation of the host cell biology by Francisella tularensis

Francisella tularensis is a facultative intracellular bacterium able to survive in mammals, arthropods, and freshwater amoeba. Little is known about the intracellular fate of F. tularensis within amoeba cells, and the role of this host-parasite adaptation in the evolution of this pathogen to infect mammals. In this study, we explored intracellular trafficking of F. tularensis subsp. novicida in Acanthamoeba castellanii cells. As previously shown by others we confirmed that F. tularensis replicates exponentially within amoeba cells, while the iglC and mglA mutants are defective. Using electron and fluorescence microscopy-based phagosome integrity assays, we show that 80% of the wild-type strain and mutants are localized within intact phagosomes during early stage of infection similar to phagosomes harboring the Legionella pneumophila control. Neither wt nor the iglC and mglA mutants escaped into the cytosol of A. castellanii infected cells by 6 h after infection. Here we show that phagosomes harboring iglC and mglA mutants co-localize with the lysoTracker dye that concentrates in acidic compartments by 2 h post infection. However, acidification of the phagosome did not occur in phagosomes containing the wt strain. Phagosomes harbouring the mglA or iglC mutants acquire the lysosomal marker, which is excluded from the phagosomes harbouring the wt strain. Here we show that F. tularensis modulates biogenesis of the phagosome in A. castellanii into niche permissive for intracellular replication. The intracellular trafficking of F. tularensis in A. castellanii shows many similarities to the processing of L. pneumophila by amoeba. Our data indicate crucial differences in modulating intracellular trafficking of F. tularensis within human macrophages and amoeba cells.

tularemia mutants; amoeba

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