The Francisella Tularensis Pathogenicity Island Encodes a Secretion System That is Required for Phagosome Escape and Virulence

Overview

Journal Mol Microbiol

Specialties Microbiology
Molecular Biology

Date 2010 Jan 8

PMID 20054881

Citations 120

Authors

Jeffrey R Barker

Audrey Chong

Tara D Wehrly

Jieh-Juen Yu

Stephen A Rodriguez

Jirong Liu

Jean Celli

Bernard P Arulanandam

Karl E Klose

Affiliations

Soon will be listed here.

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.

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