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Intracellular trafficking of pilo mutant within human macrophages and pathogenesis of tularemia in BALB/c mice

F. tularensis is a gram-negative bacterium able to adhere, invade and replicate in phagocytic and nonphagocytic cells. Many virulence factors of F. tularensis have been determined and investigated, including type IV pili (T4P). Previous results showed that type IV pili of Francisella subsp. contribute to cell adherence in BMDM, A549 and FL83B cells. However, there is no evidence of the role of pili in intracellular life of F. tularensis once inside the human macrophages. In this study transposon insertion mutant of F. novicida U112 was used to study the importance of pilO gene in virulence of bacteria on in vitro and in vivo infection models. The results of this study shows that the pilO mutant is not able to escape the Francisella containing phagosome and consequently, is attenuated for intracellular replication within human macrophages. Further, the pilO mutant was attenuated for virulence in BALB/c mice, regardless to the route of infection (intradermal or intratracheal). In contrast to the mice infected with the wt F. novicida, no histopathologic changes were obserwed in the lungs, liver and spleen of BALB/c mice inoculated i.t. or i.d. with the pilO mutant. We conclude that the pilO plays an important role in intracellular replication of F. novicida, as well as in the pathogenesis of experimental tularemia in BALB/c mice.

BALB/c mice; F.novicida; Human macrophages; pilO mutant

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