title: Phenotypic characterization of the Francisella tularensis ΔpdpC and ΔiglG mutants.
abstract: Several bacterial pathogens interact with their host through protein secretion effectuated by a type VI secretion system (T6SS). Francisella tularensis is a highly pathogenic intracellular bacterium that causes the disease tularemia. Proteins encoded by the Francisella pathogenicity island (FPI), which constitute a type VI secretion system, are essential for the virulence of the bacterium and a key mechanism behind this is the escape from the phagosome followed by productive cytosolic replication. It has been shown that T6SS in Francisella is distinct since all putative substrates of F. tularensis T6SS, except for VgrG, are unique to the species. Many of the FPI proteins are secreted into the macrophage cytosol and this is dependent on the functional components of DotU, VgrG, IglC and IglG. In addition, PdpC seems to have a regulatory role for the expression of iglABCD. Since previous results showed peculiar phenotypes of the ΔpdpC and ΔiglG mutants in mouse macrophages, their unique behavior was characterized in human monocyte-derived macrophages (HMDM) in this study. Our results show that both ΔpdpC and ΔiglG mutants of the live vaccine strain (LVS) of F. tularensis did not replicate within HMDMs. The ΔpdpC mutant did not escape from the Francisella containing phagosome (FCP), neither caused cytopathogenicity in primary macrophages and was attenuated in a mouse model. Interestingly, the ΔiglG mutant escaped from the HMDMs FCP and also caused pathological changes in the spleen and liver tissues of intradermally infected C57BL/6 mice. The ΔiglG mutant, with its unique phenotype, is a potential vaccine candidate.
authors.affiliation: Department of Microbiology and Parasitology, Faculty of Medicine, University of Rijeka, Croatia.
authors.forename: Mateja
authors.initials: M
authors.lastname: Ozanic
authors.affiliation: Department of Microbiology and Parasitology, Faculty of Medicine, University of Rijeka, Croatia.
authors.forename: Valentina
authors.initials: V
authors.lastname: Marecic
authors.affiliation: Department of Clinical Microbiology, Clinical Bacteriology and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Lindgren
authors.affiliation: Department of Clinical Microbiology, Clinical Bacteriology and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Sjöstedt
authors.affiliation: Department of Microbiology and Parasitology, Faculty of Medicine, University of Rijeka, Croatia. Electronic address: marina.santic@medri.uniri.hr.
authors.forename: Marina
authors.initials: M
authors.lastname: Santic
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D002478:Cells, Cultured; D003600:Cytosol / Q000382:microbiology; D005604:Francisella tularensis / Q000235:genetics / Q000254:growth & development / Q000276:immunology* / Q000502:physiology*; D017353:Gene Deletion; D064368:Healthy Volunteers; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D008810:Mice, Inbred C57BL; D010588:Phagosomes / Q000382:microbiology; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; C000592473:PdpC protein, Francisella tularensis; D037521:Virulence Factors
keywords: Francisella tularensis; Human macrophages; Pathogenesis in mice; iglG; pdpC