Barker Jeffrey R, Chong Audrey, Wehrly Tara D, Yu Jieh-Juen, Rodriguez Stephen A, Liu Jirong, Celli Jean, Arulanandam Bernard P, Klose Karl E
1South Texas Center for Emerging Infectious Diseases and Department of Biology, University of Texas San Antonio, San Antonio, TX, USA.
Mol Microbiol. 2009 Dec;74(6):1459-70. doi: 10.1111/j.1365-2958.2009.06947.x.
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.
土拉弗朗西斯菌可引发人类疾病兔热病。土拉弗朗西斯菌能够在巨噬细胞内存活并繁殖，这一特性与其高毒力相关，但尚不清楚该生物体在这种恶劣环境中逃避被杀伤的确切机制。土拉弗朗西斯菌的毒力依赖于弗朗西斯菌致病岛（FPI），我们在此表明，这一基因簇与霍乱弧菌和铜绿假单胞菌中的VI型分泌基因簇具有同源性。我们证明，两种FPI蛋白VgrG和IglI被分泌到被感染巨噬细胞的胞质溶胶中。VgrG和IglI是土拉弗朗西斯菌吞噬体逃逸、巨噬细胞内生长、炎性小体激活及在小鼠体内毒力所必需的。有趣的是，VgrG的分泌不需要其他FPI基因。然而，VgrG和其他FPI基因，包括PdpB（一种IcmF同源物），是IglI分泌到巨噬细胞胞质溶胶所必需的，这表明VgrG和其他FPI因子是一种分泌系统的组成部分。这是关于土拉弗朗西斯菌FPI毒力蛋白的首次报道，这些蛋白是巨噬细胞内生长所必需的，且会转移到巨噬细胞内。
