Structural Biology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Institute for Molecular Infection Biology, Julius-Maximilian University of Würzburg, Würzburg, Germany.
Nat Rev Microbiol. 2021 Sep;19(9):567-584. doi: 10.1038/s41579-021-00560-5. Epub 2021 May 26.
Type VII secretion systems (T7SSs) have a key role in the secretion of effector proteins in non-pathogenic mycobacteria and pathogenic mycobacteria such as Mycobacterium tuberculosis, the main causative agent of tuberculosis. Tuberculosis-causing mycobacteria, still accounting for 1.4 million deaths annually, rely on paralogous T7SSs to survive in the host and efficiently evade its immune response. Although it is still unknown how effector proteins of T7SSs cross the outer membrane of the diderm mycobacterial cell envelope, recent advances in the structural characterization of these secretion systems have revealed the intricate network of interactions of conserved components in the plasma membrane. This structural information, added to recent advances in the molecular biology and regulation of mycobacterial T7SSs as well as progress in our understanding of their secreted effector proteins, is shedding light on the inner working of the T7SS machinery. In this Review, we highlight the implications of these studies and the derived transport models, which provide new scenarios for targeting the deathly human pathogen M. tuberculosis.
VII 型分泌系统（T7SS）在非致病性分枝杆菌和致病性分枝杆菌（如结核分枝杆菌，结核病的主要病原体）中效应蛋白的分泌中起着关键作用。导致结核病的分枝杆菌每年仍造成 140 万人死亡，它们依赖于平行的 T7SS 在宿主中存活并有效地逃避其免疫反应。尽管 T7SS 的效应蛋白如何穿过双壁分枝杆菌细胞包膜的外膜仍然未知，但这些分泌系统的结构特征的最新进展揭示了质膜中保守成分相互作用的复杂网络。这些结构信息，加上分枝杆菌 T7SS 的分子生物学和调控方面的最新进展以及我们对其分泌效应蛋白的理解的进展，揭示了 T7SS 机械的内部工作原理。在这篇综述中，我们强调了这些研究的意义以及所推导的运输模型，这些模型为针对致命的人类病原体结核分枝杆菌提供了新的靶向场景。
