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首页> 外文期刊>Cell Reports >Hijacking Multivesicular Bodies Enables Long-Term and Exosome-Mediated Long-Distance Action of Anthrax Toxin
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Hijacking Multivesicular Bodies Enables Long-Term and Exosome-Mediated Long-Distance Action of Anthrax Toxin

机译：劫持多囊泡体可实现炭疽毒素的长期和外来体介导的远距离作用

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Anthrax lethal toxin is a classical AB toxin comprised of two components: protective antigen (PA) and lethal factor (LF). Here, we show that following assembly and endocytosis, PA forms a channel that translocates LF, not only into the cytosol, but also into the lumen of endosomal intraluminal vesicles (ILVs). These ILVs can fuse and release LF into the cytosol, where LF can proteolyze and disable host targets. We find that LF can persist in ILVs for days, fully sheltered from proteolytic degradation, both in vitro and in vivo. During this time, ILV-localized LF can be transmitted to daughter cells upon cell division. In addition, LF-containing ILVs can be delivered to the extracellular medium as exosomes. These can deliver LF to the cytosol of naive cells in a manner that is independent of the typical anthrax toxin receptor-mediated trafficking pathway, while being sheltered from neutralizing extracellular factors of the immune system.
机译：炭疽致死毒素是一种经典的AB毒素，由两个成分组成：保护性抗原（PA）和致死因子（LF）。在这里，我们表明组装和内吞后，PA形成一个通道，不仅将LF转运到细胞质中，而且还转运到了内体腔内囊泡（ILVs）的内腔中。这些ILV可以融合并释放LF到细胞质中，在LF中LF可以蛋白水解并禁用宿主靶标。我们发现LF可以在ILV中持续数天，在体外和体内都完全可以避免蛋白水解降解。在此期间，ILV定位的LF可以在细胞分裂后传输到子细胞。另外，含LF的ILV可以作为外来体递送至细胞外培养基。这些可以以不依赖于典型炭疽毒素受体介导的运输途径的方式将LF递送至幼稚细胞的细胞质，同时避免中和免疫系统的细胞外因子。

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