The Ins and Outs of Anthrax Toxin.
The Ins and Outs of Anthrax Toxin.
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DOI：
10.3390/toxins8030069
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发表时间：
2016-03-10
期刊：
影响因子：
4.2
通讯作者：
Bürgi J
中科院分区：
文献类型：
--
作者：
Friebe S;van der Goot FG;Bürgi J
炭疽是一种严重的，虽然相当罕见的传染病，是由革兰氏阳性，孢子形成细菌炭疽杆菌引起的。该菌的主要毒力因子为聚γ-D-谷氨酸荚膜和三联炭疽毒素。21世纪初炭疽毒素受体的发现使得人们能够深入研究炭疽毒素进入细胞和从内吞区室易位到细胞质的机制。该毒素通常劫持CMG 2和TEM 8（两种炭疽毒素受体）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，并使两个催化亚基移位。孔形成单位的插入优先发生在管腔内囊泡而不是内体的限制膜中，导致这些囊泡的管腔中的酶亚基的易位。这将产生重要的后果，我们将对此进行讨论。最终，毒素到达细胞溶质，在那里它们作用于各自的靶标。靶标修饰对细胞行为，特别是对免疫系统细胞具有严重后果，允许细菌传播，在严重情况下导致宿主死亡。在这里，我们将回顾炭疽病的文献，重点是毒素的结构，它如何进入细胞及其免疫效应。
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.