The interaction of Francisella tularensis with lung epithelial cells Public Deposited

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  • March 21, 2019
  • Craven, Robin Renee
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Francisella tularensis, a gram-negative facultative intracellular bacterial pathogen, is the causative agent of the disease tularemia in humans and other mammalian hosts. While tularemia can be acquired by a number of routes, the respiratory route results in the most severe disease. As few as 10 organisms can lead to pneumonic tularemia, which can have a fatality rate as high as 30-60% if untreated. Macrophages have long been considered the primary site of F. tularensis replication in infected animals, and many of the genes identified as necessary for virulence are related to survival and replication in the macrophage. However, we demonstrate that F. tularensis also invades and replicates within type II alveolar epithelial (ATII) cells in a mouse model of respiratory tularemia. We used TC-1 cells, a mouse lung epithelial cell line, to study F. tularensis invasion and intracellular trafficking within nonphagocytic cells. Live and killed F. tularensis live vaccine strain (LVS) associated with, and was internalized by, TC-1 cells with a similar frequency and kinetics. Inhibitors of microfilament and microtubule activity resulted in significantly decreased F. tularensis invasion, as did inhibitors of PI3 kinase and tyrosine kinase activity. Once internalized, F. tularensis containing endosomes associated with EEA1 then LAMP-1, followed by bacterial escape into the cytoplasm. Collectively these results suggest that F. tularensis epithelial cell invasion is mediated by a preformed ligand on the bacterial surface and driven by host cell processes, and that internalized F. tularensis trafficks along the endocytic pathway before escape into the epithelial cell cytoplasm where replication takes place.
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  • Kawula, Thomas
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  • University of North Carolina at Chapel Hill
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