Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Station 19, 1015 Lausanne, Switzerland.
Cell Rep. 2013 Nov 27;5(4):986-96. doi: 10.1016/j.celrep.2013.10.019. Epub 2013 Nov 14.
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.
炭疽致死毒素是一种经典的 AB 毒素，由两个组成部分组成：保护性抗原（PA）和致死因子（LF）。在这里，我们表明，在组装和内吞作用后，PA 形成一种通道，将 LF 不仅转运到细胞质中，还转运到内体腔内囊泡（ILV）的腔中。这些 ILV 可以融合并将 LF 释放到细胞质中，在细胞质中 LF 可以进行蛋白水解并使宿主靶标失活。我们发现，LF 可以在 ILV 中持续存在数天，完全免受蛋白水解降解的影响，无论是在体外还是体内。在此期间，ILV 定位的 LF 可以在细胞分裂时传递给子细胞。此外，含有 LF 的 ILV 可以作为外泌体被递送到细胞外培养基中。这些外泌体可以以一种不依赖于典型炭疽毒素受体介导的运输途径的方式将 LF 递送到未致敏细胞的细胞质中，同时免受免疫系统的中和细胞外因子的影响。
