Shiga Toxin Interaction with Human Intestinal Epithelium 英文参考文献.docVIP

Toxins 2011, 3, 626-639; doi:10.3390/toxins3060626 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Review Shiga Toxin Interaction with Human Intestinal Epithelium Stephanie Schüller Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK; E-Mail: stephanie.schuller@bbsrc.ac.uk; Tel.: +44-1603-255-282; Fax: +44-1603-255-288 Received: 20 April 2011; in revised form: 2 June 2011 / Accepted: 7 June 2011 / Published: 14 June 2011 Abstract: After ingestion via contaminated food or water, enterohaemorrhagic E. coli colonises the intestinal mucosa and produces Shiga toxins (Stx). No Stx-specific secretion system has been described so far, and it is assumed that Stx are released into the gut lumen after bacterial lysis. Human intestinal epithelium does not express the Stx receptor Gb3 or other Stx binding sites, and it remains unknown how Stx cross the intestinal epithelial barrier and gain access to the systemic circulation. This review summarises current knowledge about the influence of the intestinal environment on Stx production and release, Stx interaction with intestinal epithelial cells and intracellular uptake, and toxin translocation into underlying tissues. Furthermore, it highlights gaps in understanding that need to be addressed by future research. Keywords: Shiga toxin; human intestinal epithelium; regulation; intracellular transport; translocation 1. Introduction Enterohaemorrhagic E. coli (EHEC) is a major foodborne bacterial pathogen which is responsible for around 1200 cases of gastroenteritis per year in the UK. Although this constitutes only 1–3% of laboratory cases of food poisoning, EHEC infections can lead to severe systemic complications such as haemorrhagic colitis and haemolytic uraemic syndrome (HUS) which can be fatal [1]. Young children and the elderly are particularly at risk, and HUS is the leading cause of acute kidney failure in children in t