Friebe Sarah, van der Goot F Gisou, Bürgi Jérôme
Faculty of Life Sciences, Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
Toxins (Basel). 2016 Mar 10;8(3):69. doi: 10.3390/toxins8030069.
Anthrax is a severe, although rather rare, infectious disease that is caused by the Gram-positive, spore-forming bacterium Bacillus anthracis. The infectious form is the spore and the major virulence factors of the bacterium are its poly-γ-D-glutamic acid capsule and the tripartite anthrax toxin. The discovery of the anthrax toxin receptors in the early 2000s has allowed in-depth studies on the mechanisms of anthrax toxin cellular entry and translocation from the endocytic compartment to the cytoplasm. The toxin generally hijacks the endocytic pathway of CMG2 and TEM8, the two anthrax toxin receptors, in order to reach the endosomes. From there, the pore-forming subunit of the toxin inserts into endosomal membranes and enables translocation of the two catalytic subunits. Insertion of the pore-forming unit preferentially occurs in intraluminal vesicles rather than the limiting membrane of the endosome, leading to the translocation of the enzymatic subunits in the lumen of these vesicles. This has important consequences that will be discussed. Ultimately, the toxins reach the cytosol where they act on their respective targets. Target modification has severe consequences on cell behavior, in particular on cells of the immune system, allowing the spread of the bacterium, in severe cases leading to host death. Here we will review the literature on anthrax disease with a focus on the structure of the toxin, how it enters cells and its immunological effects.
炭疽是一种严重但相当罕见的传染病，由革兰氏阳性、形成芽孢的炭疽杆菌引起。具有传染性的形式是芽孢，该细菌的主要毒力因子是其多聚-γ-D-谷氨酸荚膜和三联体炭疽毒素。21世纪初炭疽毒素受体的发现使得对炭疽毒素进入细胞的机制以及从内吞区室转运至细胞质的过程能够进行深入研究。毒素通常劫持两种炭疽毒素受体CMG2和TEM8的内吞途径以到达内体。从那里，毒素的成孔亚基插入内体膜并使两个催化亚基能够转运。成孔单元的插入优先发生在腔内小泡而非内体的限制膜中，导致酶亚基在这些小泡的腔内转运。这具有重要影响，将在文中进行讨论。最终，毒素到达细胞质，在那里它们作用于各自的靶点。靶点修饰对细胞行为，特别是免疫系统的细胞行为有严重影响，使得细菌得以传播，在严重情况下导致宿主死亡。在此，我们将综述关于炭疽病的文献，重点关注毒素的结构、其进入细胞的方式及其免疫学效应。
