Belyi Yury, Niggeweg Ricarda, Opitz Bastian, Vogelsgesang Martin, Hippenstiel Stefan, Wilm Matthias, Aktories Klaus
Gamaleya Research Institute, Ulitsa Gamalei 18, Moscow 123098, Russia.
Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16953-8. doi: 10.1073/pnas.0601562103. Epub 2006 Oct 26.
Legionella pneumophila, the causal agent of Legionnaires' disease, is an intracellular parasite and invades and proliferates within different eukaryotic cells, including human alveolar macrophages. After several 100-fold multiplication within host cells, the pathogens are released for new invasion by induction of apoptosis or necrosis. Here we report that L. pneumophila produces a glucosyltransferase, which selectively modifies an approximately 50-kDa mammalian protein by using UDP-glucose as a cosubstrate. MS analysis identified the protein substrate as the mammalian elongation factor (EF)1A. Legionella glucosyltransferase modifies its eukaryotic protein substrate at serine-53, which is located in the GTPase domain of the EF. Glucosylation of EF1A results in inhibition of eukaryotic protein synthesis and death of target cells. Our findings show a mode of inhibition of protein synthesis by microbial pathogens and offer a perspective for understanding of the host-pathogen interaction of L. pneumophila.
嗜肺军团菌是军团病的病原体，是一种细胞内寄生虫，可在包括人类肺泡巨噬细胞在内的不同真核细胞内侵入并增殖。在宿主细胞内经过数百倍增殖后，病原体通过诱导凋亡或坏死而被释放出来以便再次入侵。在此我们报告，嗜肺军团菌产生一种葡糖基转移酶，该酶以UDP-葡萄糖作为共底物，选择性地修饰一种约50 kDa的哺乳动物蛋白。质谱分析确定该蛋白质底物为哺乳动物延伸因子（EF）1A。军团菌葡糖基转移酶在位于EF的GTP酶结构域中的丝氨酸-53处修饰其真核蛋白质底物。EF1A的糖基化导致真核蛋白质合成受到抑制以及靶细胞死亡。我们的研究结果显示了微生物病原体抑制蛋白质合成的一种方式，并为理解嗜肺军团菌的宿主-病原体相互作用提供了一个视角。
