title: Morphological analysis of Francisella novicida epithelial cell infections in the absence of functional FipA.
abstract: Francisella novicida is a surrogate pathogen commonly used to study infections by the potential bioterrorism agent, Francisella tularensis. One of the primary sites of Francisella infections is the liver where >90% of infected cells are hepatocytes. It is known that once Francisella enter cells it occupies a membrane-bound compartment, the Francisella-containing vacuole (FCV), from which it rapidly escapes to replicate in the cytosol. Recent work examining the Francisella disulfide bond formation (Dsb) proteins, FipA and FipB, have demonstrated that these proteins are important during the Francisella infection process; however, details as to how the infections are altered in epithelial cells have remained elusive. To identify the stage of the infections where these Dsbs might act during epithelial infections, we exploited a hepatocyte F. novicida infection model that we recently developed. We found that F. novicida ΔfipA-infected hepatocytes contained bacteria clustered within lysosome-associated membrane protein 1-positive FCVs, suggesting that FipA is involved in the escape of F. novicida from its vacuole. Our morphological evidence provides a tangible link as to how Dsb FipA can influence Francisella infections.
authors.affiliation: Department of Biological Sciences, Centre for Cell Biology, Development, and Disease, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia, V5A 1S6, Canada.
authors.forename: Karen Y
authors.identifier: http://orcid.org/0000-0003-4301-5846
authors.initials: KY
authors.lastname: Lo
authors.affiliation: Department of Biological Sciences, Centre for Cell Biology, Development, and Disease, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia, V5A 1S6, Canada.
authors.forename: Shyanne
authors.initials: S
authors.lastname: Visram
authors.affiliation: Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, 2350 Health Sciences Mall, Vancouver, V6T 1Z3, British Columbia, Canada.
authors.forename: A Wayne
authors.initials: AW
authors.lastname: Vogl
authors.affiliation: Department of Biological Sciences, Centre for Cell Biology, Development, and Disease, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia, V5A 1S6, Canada.
authors.forename: Chiao Ling Jennifer
authors.initials: CL
authors.lastname: Shen
authors.affiliation: Department of Biological Sciences, Centre for Cell Biology, Development, and Disease, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia, V5A 1S6, Canada. jguttman@sfu.ca.
authors.forename: Julian A
authors.initials: JA
authors.lastname: Guttman
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology* / Q000473:pathology* / Q000648:ultrastructure; D005603:Francisella / Q000502:physiology* / Q000648:ultrastructure; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology* / Q000473:pathology*; D022781:Hepatocytes / Q000382:microbiology / Q000473:pathology; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008807:Mice, Inbred BALB C; D009154:Mutation / Q000235:genetics; D014617:Vacuoles / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D001426:Bacterial Proteins; D051907:Lysosomal Membrane Proteins
keywords: FipA; FipB; Francisella non-phagocytic infections; Francisella-containing vacuole; Vacuole escape