Format

Send to

Choose Destination
Eur J Cell Biol. 2011 Nov;90(11):959-65. doi: 10.1016/j.ejcb.2010.10.009. Epub 2010 Dec 4.

Functional implications of lethal toxin-catalysed glucosylation of (H/K/N)Ras and Rac1 in Clostridium sordellii-associated disease.

Author information

1
Institut für Toxikologie, Medizinische Hochschule Hannover, D-30625 Hannover, Germany. genth.harald@mh-hannover.de

Abstract

Clostridium sordellii-based diseases in humans and livestock rely on the activity of the major virulence factors, the single-chain protein toxins TcsL and TcsH, both belonging to the large clostridial glucosylating toxins. TcsL exclusively glucosylates Rho and Ras low molecular weight GTP-binding proteins. TcsL-induced loss of barrier function in epithelial (diarrhoea) and endothelial cells (extravasation of blood fluid) is based on Rac glucosylation whereas induction of apoptosis results from glucosylation of Ras. Intracellular glucosylation of Rac and Ras can be tracked by immunoblot applying the glucosylation-sensitive antibodies Rac1(Mab 102) and Ras(Mab 27H5). Induction of apoptosis especially of phagocytotic cells is crucial for the severity of C. sordellii-associated disease. The inhibition of TcsL-induced apoptosis by tauroursodeoxycholic acid (TUDCA) may be a promising therapeutic option.

PMID:
21134703
DOI:
10.1016/j.ejcb.2010.10.009
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center