title: The Francisella tularensis pathogenicity island encodes a secretion system that is required for phagosome escape and virulence.
abstract: Francisella tularensis causes the human disease tularemia. F. tularensis is able to survive and replicate within macrophages, a trait that has been correlated with its high virulence, but it is unclear the exact mechanism(s) this organism uses to escape killing within this hostile environment. F. tularensis virulence is dependent upon the Francisella pathogenicity island (FPI), a cluster of genes that we show here shares homology with type VI secretion gene clusters in Vibrio cholerae and Pseudomonas aeruginosa. We demonstrate that two FPI proteins, VgrG and IglI, are secreted into the cytosol of infected macrophages. VgrG and IglI are required for F. tularensis phagosomal escape, intramacrophage growth, inflammasome activation and virulence in mice. Interestingly, VgrG secretion does not require the other FPI genes. However, VgrG and other FPI genes, including PdpB (an IcmF homologue), are required for the secretion of IglI into the macrophage cytosol, suggesting that VgrG and other FPI factors are components of a secretion system. This is the first report of F. tularensis FPI virulence proteins required for intramacrophage growth that are translocated into the macrophage.
authors.affiliation: 1South Texas Center for Emerging Infectious Diseases and Department of Biology, University of Texas San Antonio, San Antonio, TX, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Barker
authors.forename: Audrey
authors.initials: A
authors.lastname: Chong
authors.forename: Tara D
authors.initials: TD
authors.lastname: Wehrly
authors.forename: Jieh-Juen
authors.initials: JJ
authors.lastname: Yu
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Rodriguez
authors.forename: Jirong
authors.initials: J
authors.lastname: Liu
authors.forename: Jean
authors.initials: J
authors.lastname: Celli
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Arulanandam
authors.forename: Karl E
authors.initials: KE
authors.lastname: Klose
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D005260:Female; D005604:Francisella tularensis / Q000235:genetics / Q000472:pathogenicity*; D005798:Genes, Bacterial; D044404:Genomic Islands; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050296:Microbial Viability; D005810:Multigene Family; D010588:Phagosomes / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics; D014406:Tularemia / Q000382:microbiology; D014734:Vibrio cholerae / Q000235:genetics; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D037521:Virulence Factors