Department of Molecular Pathology and Biology, Faculty of Military Health Sciences, University of Defence, Trebesska1575, Hradec Kralove, Czech Republic.
CIRI, International Center for Infectiology Research, Inserm U1111, UMR5308, CNRS, Lyon, France.
Sci Rep. 2020 Sep 3;10(1):14612. doi: 10.1038/s41598-020-71641-3.
Francisella tularensis is a highly virulent intracellular bacterium and the causative agent of tularemia. The disease is characterized by the suboptimal innate immune response and consequently by the impaired adaptive immunity. The virulence of this pathogen depends on proteins encoded by a genomic island termed the Francisella Pathogenicity Island (FPI). However, the precise biological roles of most of the FPI-encoded proteins remain to be clarified. In this study, we employed stable isotope labeling by amino acids in cell culture (SILAC) in combination with affinity protein purification coupled with liquid chromatography-mass spectrometry to identify potential protein-effector binding pairs for two FPI virulence effectors IglJ and VgrG. Our results may indicate that while the IglJ protein interactions primarily affect mitochondria, the VgrG interactions affect phagosome and/or autophagosome biogenesis via targeting components of the host's exocyst complex.
土拉弗朗西斯菌是一种高度毒力的细胞内细菌，也是土拉菌病的病原体。这种疾病的特征是先天免疫反应不佳，随后适应性免疫受到损害。该病原体的毒力取决于一个被称为弗朗西斯菌致病性岛（FPI）的基因组岛上编码的蛋白质。然而，大多数 FPI 编码蛋白的确切生物学作用仍有待阐明。在这项研究中，我们使用了稳定同位素标记的氨基酸在细胞培养中的应用（SILAC），结合亲和蛋白纯化和液相色谱-质谱联用，以鉴定两个 FPI 毒力效应蛋白 IglJ 和 VgrG 的潜在蛋白效应物结合对。我们的结果可能表明，虽然 IglJ 蛋白相互作用主要影响线粒体，但 VgrG 相互作用通过靶向宿主的外泌体复合物的成分来影响吞噬体和/或自噬体的生物发生。
