Fabry disease in mice protects against lethal disease caused by Shiga toxin-expressing enterohemorrhagic Escherichia coli. Academic Article uri icon

Overview

abstract

  • Fabry disease is an X-linked recessive disorder in which affected persons lack alpha-galactosidase A (alpha -GalA), which leads to excess glycosphingolipids in tissues, mainly globotriaosylceramide (Gb3). Gb3 is the cellular receptor for Shiga toxin (Stx), the primary virulence factor of enterohemorrhagic Escherichia coli. alpha-GalA-knockout mice were significantly protected against lethal intraperitoneal doses of Stx2 or oral doses of Stx2-expressing bacteria, compared with wild-type (wt) control mice. Kidneys of moribund wt mice revealed tubular necrosis, but no histopathologic changes were observed in Gb3-overexpressing mice. Reducing Gb3 levels in alpha-GalA-knockout mice by the intravenous injection of recombinant human alpha-GalA restored the susceptibility of knockout mice to lethal doses of Stx2. These results suggest that excess amounts of Gb3 in alpha-GalA-deficient mice may impair toxin delivery to susceptible tissues.

publication date

  • September 8, 2006

Research

keywords

  • Escherichia coli Infections
  • Escherichia coli O157
  • Fabry Disease
  • Kidney
  • Shiga Toxins

Identity

Scopus Document Identifier

  • 33749629725

Digital Object Identifier (DOI)

  • 10.1086/507705

PubMed ID

  • 16991089

Additional Document Info

volume

  • 194

issue

  • 8