Exosome-associated Shiga toxin 2 is released from cells and causes severe toxicity in mice.
Exosome-associated Shiga toxin 2 is released from cells and causes severe toxicity in mice.
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DOI：
10.1038/s41598-018-29128-9
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发表时间：
2018-07-17
影响因子：
4.6
通讯作者：
Nishikawa K
中科院分区：
文献类型：
--
作者：
Watanabe-Takahashi M;Yamasaki S;Murata M;Kano F;Motoyama J;Yamate J;Omi J;Sato W;Ukai H;Shimasaki K;Ikegawa M;Tamura-Nakano M;Yanoshita R;Nishino Y;Miyazawa A;Natori Y;Toyama-Sorimachi N;Nishikawa K
志贺毒素（Stx）是肠出血性大肠杆菌（EHEC）的主要毒力因子，分为Stx1和Stx2两个亚群。临床数据清楚地表明，Stx2比Stx1具有更严重的毒性，但这种差异背后的分子机制尚不完全清楚。在这里，我们发现Stx2被纳入靶细胞后，可以通过循环内体运输，也可以通过常规的逆行运输途径运输。然而，Stx1没有通过再循环核内体进行转运。我们还发现Stx2以受体识别b亚基依赖的方式从细胞中主动释放。部分释放的Stx2与微泡有关，包括外泌体标记物（称为exo-Stx2），其起源是由晚期/循环内体形成的多泡体。最后，与游离形式的Stx2相比，静脉注射exo-Stx2对小鼠造成更大的致死率和组织损伤，尤其是严重的肾功能障碍和小管上皮细胞损伤。因此，exo-Stx2的形成可能有助于体内Stx2的严重程度，提示针对肠出血性大肠杆菌感染的新治疗策略。
Shiga toxin (Stx), a major virulence factor of enterohemorrhagic Escherichia coli (EHEC), is classified into two subgroups, Stx1 and Stx2. Clinical data clearly indicate that Stx2 is associated with more severe toxicity than Stx1, but the molecular mechanism underlying this difference is not fully understood. Here, we found that after being incorporated into target cells, Stx2, can be transported by recycling endosomes, as well as via the regular retrograde transport pathway. However, transport via recycling endosome did not occur with Stx1. We also found that Stx2 is actively released from cells in a receptor-recognizing B-subunit dependent manner. Part of the released Stx2 is associated with microvesicles, including exosome markers (referred to as exo-Stx2), whose origin is in the multivesicular bodies that formed from late/recycling endosomes. Finally, intravenous administration of exo-Stx2 to mice causes more lethality and tissue damage, especially severe renal dysfunction and tubular epithelial cell damage, compared to a free form of Stx2. Thus, the formation of exo-Stx2 might contribute to the severity of Stx2 in vivo, suggesting new therapeutic strategies against EHEC infections.
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影响因子：
6.1
作者：
Ge, Shuwang;Hertel, Barbara;von Vietinghoff, Sibylle
通讯作者：
von Vietinghoff, Sibylle
影响因子：
11.4
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影响因子：
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Gyles, CL
影响因子：
3.3
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通讯作者：
Gyles, C. L.
影响因子：
4.8
作者：
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通讯作者：
Budnik, Vivian