Reactive Oxygen Species as Additional Determinants for Cytotoxicity of Clostridium difficile Toxins A and B

Clostridium difficile infections can induce mild to severe diarrhoea and the often associated characteristic pseudomembranous colitis. Two protein toxins, the large glucosyltransferases TcdA and TcdB, are the main pathogenicity factors that can induce all clinical symptoms in animal models. The clas...

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Bibliographic Details
Published in:Toxins 2016-01, Vol.8 (1), p.25
Main Authors: Frädrich, Claudia, Beer, Lara-Antonia, Gerhard, Ralf
Format: Article
Language:English
Subjects:
Animals
Bacterial Proteins - toxicity
Bacterial Toxins - toxicity
Cell Death
Clostridium difficile infection
cytotoxicity
Enterotoxins - toxicity
Humans
NADPH oxidase
neutrophils
reactive oxygen species
Reactive Oxygen Species - metabolism
Review
Rho GTPases
toxin
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Summary:Clostridium difficile infections can induce mild to severe diarrhoea and the often associated characteristic pseudomembranous colitis. Two protein toxins, the large glucosyltransferases TcdA and TcdB, are the main pathogenicity factors that can induce all clinical symptoms in animal models. The classical molecular mode of action of these homologous toxins is the inhibition of Rho GTPases by mono-glucosylation. Rho-inhibition leads to breakdown of the actin cytoskeleton, induces stress-activated and pro-inflammatory signaling and eventually results in apoptosis of the affected cells. An increasing number of reports, however, have documented further qualities of TcdA and TcdB, including the production of reactive oxygen species (ROS) by target cells. This review summarizes observations dealing with the production of ROS induced by TcdA and TcdB, dissects pathways that contribute to this phenomenon and speculates about ROS in mediating pathogenesis. In conclusion, ROS have to be considered as a discrete, glucosyltransferase-independent quality of at least TcdB, triggered by different mechanisms.
ISSN:2072-6651
2072-6651
DOI:10.3390/toxins8010025