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A Novel Mechanism of Bacterial Toxin Transfer within Host Blood Cell-Derived Microvesicles.

Ståhl, Anne-lie LU ; Arvidsson, Ida LU ; Johansson, Karl LU ; Chromek, Milan LU ; Rebetz, Johan LU ; Loos, Sebastian LU ; Kristoffersson, Ann-Charlotte LU ; Békassy, Zivile LU ; Mörgelin, Matthias LU and Karpman, Diana LU (2015) In PLoS Pathogens 11(2).
Abstract
Shiga toxin (Stx) is the main virulence factor of enterohemorrhagic Escherichia coli, which are non-invasive strains that can lead to hemolytic uremic syndrome (HUS), associated with renal failure and death. Although bacteremia does not occur, bacterial virulence factors gain access to the circulation and are thereafter presumed to cause target organ damage. Stx was previously shown to circulate bound to blood cells but the mechanism by which it would potentially transfer to target organ cells has not been elucidated. Here we show that blood cell-derived microvesicles, shed during HUS, contain Stx and are found within patient renal cortical cells. The finding was reproduced in mice infected with Stx-producing Escherichia coli exhibiting... (More)
Shiga toxin (Stx) is the main virulence factor of enterohemorrhagic Escherichia coli, which are non-invasive strains that can lead to hemolytic uremic syndrome (HUS), associated with renal failure and death. Although bacteremia does not occur, bacterial virulence factors gain access to the circulation and are thereafter presumed to cause target organ damage. Stx was previously shown to circulate bound to blood cells but the mechanism by which it would potentially transfer to target organ cells has not been elucidated. Here we show that blood cell-derived microvesicles, shed during HUS, contain Stx and are found within patient renal cortical cells. The finding was reproduced in mice infected with Stx-producing Escherichia coli exhibiting Stx-containing blood cell-derived microvesicles in the circulation that reached the kidney where they were transferred into glomerular and peritubular capillary endothelial cells and further through their basement membranes followed by podocytes and tubular epithelial cells, respectively. In vitro studies demonstrated that blood cell-derived microvesicles containing Stx undergo endocytosis in glomerular endothelial cells leading to cell death secondary to inhibited protein synthesis. This study demonstrates a novel virulence mechanism whereby bacterial toxin is transferred within host blood cell-derived microvesicles in which it may evade the host immune system. (Less)
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published
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PLoS Pathogens
volume
11
issue
2
publisher
Public Library of Science
external identifiers
  • pmid:25719452
  • wos:000352083400012
  • scopus:84924405786
ISSN
1553-7366
DOI
10.1371/journal.ppat.1004619
language
English
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yes
id
271119f6-ca07-405a-82bc-522ed31492b9 (old id 5142639)
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http://www.ncbi.nlm.nih.gov/pubmed/25719452?dopt=Abstract
date added to LUP
2015-03-11 17:07:08
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2017-11-12 03:10:36
@article{271119f6-ca07-405a-82bc-522ed31492b9,
  abstract     = {Shiga toxin (Stx) is the main virulence factor of enterohemorrhagic Escherichia coli, which are non-invasive strains that can lead to hemolytic uremic syndrome (HUS), associated with renal failure and death. Although bacteremia does not occur, bacterial virulence factors gain access to the circulation and are thereafter presumed to cause target organ damage. Stx was previously shown to circulate bound to blood cells but the mechanism by which it would potentially transfer to target organ cells has not been elucidated. Here we show that blood cell-derived microvesicles, shed during HUS, contain Stx and are found within patient renal cortical cells. The finding was reproduced in mice infected with Stx-producing Escherichia coli exhibiting Stx-containing blood cell-derived microvesicles in the circulation that reached the kidney where they were transferred into glomerular and peritubular capillary endothelial cells and further through their basement membranes followed by podocytes and tubular epithelial cells, respectively. In vitro studies demonstrated that blood cell-derived microvesicles containing Stx undergo endocytosis in glomerular endothelial cells leading to cell death secondary to inhibited protein synthesis. This study demonstrates a novel virulence mechanism whereby bacterial toxin is transferred within host blood cell-derived microvesicles in which it may evade the host immune system.},
  articleno    = {e1004619},
  author       = {Ståhl, Anne-lie and Arvidsson, Ida and Johansson, Karl and Chromek, Milan and Rebetz, Johan and Loos, Sebastian and Kristoffersson, Ann-Charlotte and Békassy, Zivile and Mörgelin, Matthias and Karpman, Diana},
  issn         = {1553-7366},
  language     = {eng},
  number       = {2},
  publisher    = {Public Library of Science},
  series       = {PLoS Pathogens},
  title        = {A Novel Mechanism of Bacterial Toxin Transfer within Host Blood Cell-Derived Microvesicles.},
  url          = {http://dx.doi.org/10.1371/journal.ppat.1004619},
  volume       = {11},
  year         = {2015},
}