Anthrax lethal toxin is a classical AB toxin comprisedof two components: protective antigen (PA) andlethal factor (LF). Here, we show that followingassembly and endocytosis, PA forms a channel thattranslocates LF, not only into the cytosol, but alsointo the lumen of endosomal intraluminal vesicles(ILVs). These ILVs can fuse and release LF into thecytosol, where LF can proteolyze and disable hosttargets. We find that LF can persist in ILVs for days,fully sheltered from proteolytic degradation, bothin vitro and in vivo. During this time, ILV-localizedLF can be transmitted to daughter cells upon celldivision. In addition, LF-containing ILVs can be deliv-ered to the extracellular medium as exosomes.These can deliver LF to the cytosol of naive cells ina manner that is independent of the typical anthraxtoxin receptor-mediated trafficking pathway, whilebeing sheltered from neutralizing extracellular fac-tors of the immune system.
A publication of Laurence Abrami, Lucia Brandi, Mahtab Moayeri, Michael J. Brown, Bryan A. Krantz, Stephen H. Leppla, and F. Gisou van der Goot.
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