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

Toxins
Claudia FrädrichRalf Gerhard

Abstract

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.

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Citations

Aug 31, 2016·Nature Reviews. Microbiology·Michael C AbtEric G Pamer
May 18, 2021·Frontiers in Molecular Biosciences·Alistair Tweedie, Tracy Nissan

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Methods Mentioned

BETA
GTPases
glucosylation
GTPase
nucleotide exchange
deamination

Software Mentioned

ClosTron

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

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