PMID- 24239351
OWN - NLM
STAT- MEDLINE
DCOM- 20140819
LR  - 20211021
IS  - 2211-1247 (Electronic)
VI  - 5
IP  - 4
DP  - 2013 Nov 27
TI  - Hijacking multivesicular bodies enables long-term and exosome-mediated 
      long-distance action of anthrax toxin.
PG  - 986-96
LID - S2211-1247(13)00603-7 [pii]
LID - 10.1016/j.celrep.2013.10.019 [doi]
AB  - 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.
CI  - Copyright (c) 2013 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Abrami, Laurence
AU  - Abrami L
AD  - Global Health Institute, Ecole Polytechnique Federale de Lausanne, Station 19, 
      1015 Lausanne, Switzerland.
FAU - Brandi, Lucia
AU  - Brandi L
FAU - Moayeri, Mahtab
AU  - Moayeri M
FAU - Brown, Michael J
AU  - Brown MJ
FAU - Krantz, Bryan A
AU  - Krantz BA
FAU - Leppla, Stephen H
AU  - Leppla SH
FAU - van der Goot, F Gisou
AU  - van der Goot FG
LA  - eng
GR  - R01 AI077703/AI/NIAID NIH HHS/United States
GR  - Z99 AI999999/Intramural NIH HHS/United States
GR  - 2R01 AI077703-05/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20131114
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Bacterial Toxins)
RN  - 0 (Protein Subunits)
RN  - 0 (anthrax toxin)
SB  - IM
MH  - Animals
MH  - Antigens, Bacterial/pharmacology
MH  - Bacillus anthracis/pathogenicity
MH  - Bacterial Toxins/*pharmacokinetics/pharmacology
MH  - Cell Line
MH  - Cytosol/immunology/metabolism
MH  - Endocytosis
MH  - Exosomes/metabolism
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Multivesicular Bodies/*metabolism
MH  - Protein Subunits/metabolism
MH  - Protein Transport
PMC - PMC3866279
MID - NIHMS532575
EDAT- 2013/11/19 06:00
MHDA- 2014/08/20 06:00
PMCR- 2013/12/17
CRDT- 2013/11/19 06:00
PHST- 2013/07/16 00:00 [received]
PHST- 2013/10/01 00:00 [revised]
PHST- 2013/10/11 00:00 [accepted]
PHST- 2013/11/19 06:00 [entrez]
PHST- 2013/11/19 06:00 [pubmed]
PHST- 2014/08/20 06:00 [medline]
PHST- 2013/12/17 00:00 [pmc-release]
AID - S2211-1247(13)00603-7 [pii]
AID - 10.1016/j.celrep.2013.10.019 [doi]
PST - ppublish
SO  - Cell Rep. 2013 Nov 27;5(4):986-96. doi: 10.1016/j.celrep.2013.10.019. Epub 2013 
      Nov 14.