MgIA regulates transcription of virulence factors necessary for Francisella tularensis intraamoebae and intramacrophage survival

Francisella tularensis is able to survive and grow within macrophages, a trait that contributes to pathogenesis. Several genes have been identified that are important for intramacrophage survival, including mgIA and igIC. F. tularensis is also able to survive within amoebae. It is shown here that F. tularensis mgIA and igIC mutant strains are not only defective for survival and replication within the macrophage-like cell line J774, but also within Acanthamoebae castellanii. Moreover, these strains are highly attenuated for virulence in mice, suggesting that a common mechanism underlies intramacrophage and intraamoebae survival and virulence. A 2D gel analysis of cell extracts of wild-type and mgIA mutant strains revealed that at least seven prominent proteins were at low levels in the mgIA mutant, and one MgIA-regulated protein was identified as the IgIC protein. RT-PCR analysis demonstrated reduced transcription of igIC and several other known and suspected virulence genes in the mgIA mutant. Thus, MgIA regulates the transcription of virulence factors of F. tularensis that contribute to intramacrophage and intraamoebae survival.