Research Institute for Microbial Diseases, Osaka University, Yamadaoka 3-1, Suita, Osaka, 565-0871, Japan.
Curr Top Microbiol Immunol. 2013;376:227-47. doi: 10.1007/82_2013_343.
The bacterial pathogen Legionella pneumophila manipulates its intracellular fate by co-opting host processes. Using bacterial proteins translocated into host cells, L. pneumophila targets pathways shared by unicellular protozoa and higher eukaryotes. In eukaryotes, an important mechanism that regulates numerous cellular processes, including those designed to kill invading microorganisms, is ubiquitination. Post-translational modification of proteins with ubiquitin is a highly regulated process that either targets proteins for degradation or modifies their activity. It is emerging that L. pneumophila possesses functional mimics of eukaryotic E3 ubiquitin ligases that function with the host ubiquitination machinery to select and modify substrates for polyubiquitination. L. pneumophila proteins have been identified that ubiquitinate both host and bacterial proteins, and ubiquitination of the bacterial protein SidH results in its degradation by the host proteasome. This pathway allows L. pneumophila to temporally regulate effector function inside host cells, and facilitates optimal L. pneumophila replication by undefined mechanisms. This review will focus on our current knowledge of the proteins used by L. pneumophila to co-opt the host ubiquitination machinery, and current progress toward understanding the ubiquitin-mediated processes manipulated by L. pneumophila to facilitate intracellular survival and propagation.
细菌病原体嗜肺军团菌通过利用宿主过程来操纵其细胞内命运。嗜肺军团菌利用细菌蛋白易位进入宿主细胞，靶向单细胞原生动物和高等真核生物共享的途径。在真核生物中，泛素化是一种重要的调节机制，可调节包括杀死入侵微生物的多种细胞过程。越来越多的证据表明，嗜肺军团菌具有真核 E3 泛素连接酶的功能模拟物，这些模拟物与宿主泛素化机制一起作用，以选择和修饰多泛素化的底物。已经鉴定出嗜肺军团菌蛋白可泛素化宿主和细菌蛋白，并且细菌蛋白 SidH 的泛素化导致其被宿主蛋白酶体降解。该途径使嗜肺军团菌能够在宿主细胞内临时调节效应子功能，并通过未知机制促进嗜肺军团菌的最佳复制。本综述将重点介绍我们目前对嗜肺军团菌用于篡夺宿主泛素化机制的蛋白质的了解，以及目前在理解嗜肺军团菌操纵的泛素介导过程以促进细胞内存活和繁殖方面的进展。
