TY - JOUR
T1 - The Francisella tularensis pathogenicity island encodes a secretion system that is required for phagosome escape and virulence
AU - Barker, Jeffrey R.
AU - Chong, Audrey
AU - Wehrly, Tara D.
AU - Yu, Jieh Juen
AU - Rodriguez, Stephen A.
AU - Liu, Jirong
AU - Celli, Jean
AU - Arulanandam, Bernard P.
AU - Klose, Karl E.
PY - 2009/12
Y1 - 2009/12
N2 - 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.
AB - 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.
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U2 - 10.1111/j.1365-2958.2009.06947.x
DO - 10.1111/j.1365-2958.2009.06947.x
M3 - Article
C2 - 20054881
AN - SCOPUS:72049089849
VL - 74
SP - 1459
EP - 1470
JO - Molecular Microbiology
JF - Molecular Microbiology
SN - 0950-382X
IS - 6
ER -