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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Mikrobiologi inom det medicinska området
Originalspråkengelska
Artikelnummere1004619
TidskriftPLoS Pathogens
Volym11
Utgivningsnummer2
StatusPublished - 2015
PublikationskategoriForskning
Peer review utfördJa

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Relaterad forskningsoutput

Ida Arvidsson, 2015, Paediatrics, Faculty of Medicine, Lund University. 96 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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