Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Purdue Institute for Inflammation, Immunology, and Infectious Disease and Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
Cell Rep. 2017 Nov 21;21(8):2031-2038. doi: 10.1016/j.celrep.2017.10.088.
All pathogens must acquire nutrients from their hosts. The intracellular bacterial pathogen Legionella pneumophila, the etiological agent of Legionnaires' disease, requires host amino acids for growth within cells. The mechanistic target of rapamycin complex 1 (mTORC1) is an evolutionarily conserved master regulator of host amino acid metabolism. Here, we identify two families of translocated L. pneumophila effector proteins that exhibit opposing effects on mTORC1 activity. The Legionella glucosyltransferase (Lgt) effector family activates mTORC1, through inhibition of host translation, whereas the SidE/SdeABC (SidE) effector family acts as mTORC1 inhibitors. We demonstrate that a common activity of both effector families is to inhibit host translation. We propose that the Lgt and SidE families of effectors work in concert to liberate host amino acids for consumption by L. pneumophila.
所有病原体都必须从宿主中获取营养。细胞内细菌病原体嗜肺军团菌是军团病的病原体，它需要宿主氨基酸才能在细胞内生长。雷帕霉素复合物 1（mTORC1）是一种进化上保守的宿主氨基酸代谢的主要调节剂。在这里，我们鉴定了两类易位的嗜肺军团菌效应蛋白，它们对 mTORC1 活性表现出相反的影响。军团菌葡萄糖基转移酶（Lgt）效应家族通过抑制宿主翻译来激活 mTORC1，而 SidE/SdeABC（SidE）效应家族则作为 mTORC1 抑制剂。我们证明，这两种效应家族的共同活性是抑制宿主翻译。我们提出，Lgt 和 SidE 效应家族协同作用，释放宿主氨基酸供嗜肺军团菌消耗。
