Abstract
The pathogenicity of Clostridium difficile depends on the large clostridial glucosylating toxins A and B (TcdA and TcdB). The proteins accomplish their own uptake by a modular structure comprising a catalytic and a binding/translocation domain. Based on a proteolytic processing step solely the catalytic domain reaches the cytosol. Within the cells, the glucosyltransferases inactivate small GTPases by mono-O-glucosylation. Here, a short overview is given regarding latest insights into the intramolecular processing, which is mediated by an intrinsic protease activity.
Highlights
Nosocomial infections with Clostridium difficile often occur during antibiotic therapy
The primary sequence of toxin B aa 544–955, a fragment bordered by the N-terminal glucosyltransferase domain (‘GT’) and the hydrophobic, putative transmembrane region (‘HR’, aa 956–1128; see Fig. 1, upper panel) displays a striking sequence similarity to repeat in toxin (RTX) protein toxins and autotransporter adhesins from, for example, Vibrio cholerae and Vibrio vulnificus/Vibrio splendidus
A major step forward was made with the finding of an intrinsic proteolytic activity of the toxins. This autoproteolytic activity is induced by InsP6 and/or DTT and is responsible for the separation of the catalytic domain from the holotoxin (Reineke et al, 2007; Egerer et al, 2007)
Summary
Institut fur Experimentelle und Klinische Pharmakologie und Toxikologie, Universitat Freiburg, Albertstrasse 25, D-79104 Freiburg, Germany. The pathogenicity of Clostridium difficile depends on the large clostridial glucosylating toxins A and B (TcdA and TcdB). The proteins accomplish their own uptake by a modular structure comprising a catalytic and a binding/translocation domain. Based on a proteolytic processing step solely the catalytic domain reaches the cytosol. The glucosyltransferases inactivate small GTPases by mono-O-glucosylation. A short overview is given regarding latest insights into the intramolecular processing, which is mediated by an intrinsic protease activity
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