title: IglG and IglI of the Francisella pathogenicity island are important virulence determinants of Francisella tularensis LVS.
abstract: The Gram-negative bacterium Francisella tularensis is the causative agent of tularemia, a disease intimately associated with the multiplication of the bacterium within host macrophages. This in turn requires the expression of Francisella pathogenicity island (FPI) genes, believed to encode a type VI secretion system. While the exact functions of many of the components have yet to be revealed, some have been found to contribute to the ability of Francisella to cause systemic infection in mice as well as to prevent phagolysosomal fusion and facilitate escape into the host cytosol. Upon reaching this compartment, the bacterium rapidly multiplies, inhibits activation of the inflammasome, and ultimately causes apoptosis of the host cell. In this study, we analyzed the contribution of the FPI-encoded proteins IglG, IglI, and PdpE to the aforementioned processes in F. tularensis LVS. The ΔpdpE mutant behaved similarly to the parental strain in all investigated assays. In contrast, ΔiglG and ΔiglI mutants, although they were efficiently replicating in J774A.1 cells, both exhibited delayed phagosomal escape, conferred a delayed activation of the inflammasome, and exhibited reduced cytopathogenicity as well as marked attenuation in the mouse model. Thus, IglG and IglI play key roles for modulation of the intracellular host response and also for the virulence of F. tularensis.
authors.affiliation: Department of Clinical Microbiology, Clinical Bacteriology, Umeå University, SE-901 85 Umeå, Sweden. jeanette.broms@climi.umu.se
authors.forename: Jeanette E
authors.initials: JE
authors.lastname: Bröms
authors.forename: Moa
authors.initials: M
authors.lastname: Lavander
authors.forename: Lena
authors.initials: L
authors.lastname: Meyer
authors.forename: Anders
authors.initials: A
authors.lastname: Sjöstedt
mesh_terms: D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000235:genetics; D058947:Bacterial Secretion Systems / Q000235:genetics; D002460:Cell Line; D005604:Francisella tularensis / Q000235:genetics* / Q000472:pathogenicity*; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D044404:Genomic Islands; D058847:Inflammasomes / Q000502:physiology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D010587:Phagocytosis / Q000235:genetics; D010588:Phagosomes / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D014406:Tularemia / Q000382:microbiology / Q000473:pathology; D037521:Virulence Factors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D058847:Inflammasomes; D037521:Virulence Factors