title: Factors affecting the escape of Francisella tularensis from the phagolysosome.
abstract: The highly virulent bacterium Francisella tularensis is well adapted to the intracellular habitat but the mechanisms behind its intracellular survival have been elusive. Recently, it was shown that the bacterium is capable of escaping from the phagosome of human and mouse monocytic cells. Here it is shown that this escape is affected by gamma interferon (IFN-gamma) treatment of mouse peritoneal exudate cells since in treated cells the proportion that escaped was significantly lower (80%) than in untreated cells (97%) as determined by transmission electron microscopy. By contrast, < 1% of mutant bacteria lacking expression of a 23 kDa protein denoted IglC were able to escape from the phagosome. Infection with the DeltaiglC strain complemented with the iglC gene resulted in 60% of the bacteria escaping from the phagosome. Whereas IFN-gamma treatment conferred a static effect on intracellular wild-type bacteria, the treatment had a bactericidal effect on the DeltaiglC strain. The results show that the activation status of infected cells affects the escape of F. tularensis from the phagosome. An even more profound effect on this escape is related to expression of IglC by F. tularensis. Its absence rendered the mutant bacteria incapable of escaping from the phagosome and of multiplying intracellularly.
authors.affiliation: Department of Clinical Microbiology, Clinical Bacteriology1, and Department of Clinical Microbiology, Immunology2, Umeå University, Umeå, Sweden 3Departments of Medicine and Microbiology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Helena
authors.initials: H
authors.lastname: Lindgren
authors.affiliation: Department of Clinical Microbiology, Clinical Bacteriology1, and Department of Clinical Microbiology, Immunology2, Umeå University, Umeå, Sweden 3Departments of Medicine and Microbiology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Golovliov
authors.affiliation: Department of Clinical Microbiology, Clinical Bacteriology1, and Department of Clinical Microbiology, Immunology2, Umeå University, Umeå, Sweden 3Departments of Medicine and Microbiology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Baranov
authors.affiliation: Department of Clinical Microbiology, Clinical Bacteriology1, and Department of Clinical Microbiology, Immunology2, Umeå University, Umeå, Sweden 3Departments of Medicine and Microbiology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Ernst
authors.affiliation: Department of Clinical Microbiology, Clinical Bacteriology1, and Department of Clinical Microbiology, Immunology2, Umeå University, Umeå, Sweden 3Departments of Medicine and Microbiology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Max
authors.initials: M
authors.lastname: Telepnev
authors.affiliation: Department of Clinical Microbiology, Clinical Bacteriology1, and Department of Clinical Microbiology, Immunology2, Umeå University, Umeå, Sweden 3Departments of Medicine and Microbiology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Anders
authors.initials: A
authors.lastname: Sjöstedt
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology; D005604:Francisella tularensis / Q000737:chemistry / Q000254:growth & development / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology; D008055:Lipids / Q000032:analysis; D051379:Mice; D008854:Microscopy, Electron; D010588:Phagosomes / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D008055:Lipids; D007371:Interferon-gamma