Department of Molecular Genetics, University of Toronto, Toronto, ON M5G1M1, Canada.
Int J Mol Sci. 2020 Jun 2;21(11):3985. doi: 10.3390/ijms21113985.
The clinically important () and related mycobacterial pathogens use various virulence mechanisms to survive and cause disease in their hosts. Several well-established virulence factors include the surface-exposed lipids in the mycobacterial outer membrane, as well as the Esx family proteins and the Pro-Glu (PE)/ Pro-Pro-Glu (PPE) family proteins secreted by type VII secretion systems (T7SS). Five ESX T7SS exist in and three-EsxA secretion system-1 (ESX-1), ESX-3, and ESX-5-have been implicated in virulence, yet only the structures of ESX-3 and ESX-5 have been solved to date. Here, we summarize the current research on three outer membrane lipids-phthiocerol dimycocerosates, phenolic glycolipids, and sulfolipids-as well as the secretion machinery and substrates of three mycobacterial T7SS-ESX-1, ESX-3, and ESX-5. We propose a structural model of the ESX-1 system based on the latest structural findings of the ESX-3 and ESX-5 secretion apparatuses to gain insight into the transport mechanism of ESX-associated virulence factors.
临床重要的 () 和相关分枝杆菌病原体利用各种毒力机制在宿主中存活并引起疾病。几个成熟的毒力因子包括分枝杆菌外膜表面暴露的脂质，以及 VII 型分泌系统 (T7SS) 分泌的 Esx 家族蛋白和 Pro-Glu (PE)/Pro-Pro-Glu (PPE) 家族蛋白。 和 中存在五个 ESX T7SS，三个-EsxA 分泌系统-1 (ESX-1)、ESX-3 和 ESX-5-与毒力有关，但迄今为止仅解决了 ESX-3 和 ESX-5 的结构。在这里，我们总结了三种外膜脂质-双分枝菌酸焦磷酸二酯、酚甘油醚和硫脂，以及三种分枝杆菌 T7SS-ESX-1、ESX-3 和 ESX-5 的分泌机制和底物的最新研究进展。我们根据 ESX-3 和 ESX-5 分泌装置的最新结构发现，提出了一个基于结构的 ESX-1 系统模型，以深入了解 ESX 相关毒力因子的运输机制。
