Glucosylation of Rho GTPases by Clostridium difficile toxin A triggers apoptosis in intestinal epithelial cells.
@article{Gerhard2008GlucosylationOR, title={Glucosylation of Rho GTPases by Clostridium difficile toxin A triggers apoptosis in intestinal epithelial cells.}, author={Ralf Gerhard and Stefanie Nottrott and Janett Schoentaube and Helma Tatge and Alexandra Olling and Ingo Just}, journal={Journal of medical microbiology}, year={2008}, volume={57 Pt 6}, pages={ 765-70 } }
The intestinal epithelial cell line HT-29 was used to study the apoptotic effect of Clostridium difficile toxin A (TcdA). TcdA is a 300 kDa single-chain protein, which glucosylates and thereby inactivates small GTPases of the Rho family (Rho, Rac and Cdc42). The effect of TcdA-catalysed glucosylation of the Rho GTPases is well known: reorganization of the actin cytoskeleton with accompanying morphological changes in cells, leading to complete rounding of cells and destruction of the intestinal…
93 Citations
Substrate specificity of clostridial glucosylating toxins and their function on colonocytes analyzed by proteomics techniques.
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- Biology, MedicineToxins
- 2015
This review focuses on recent progresses in the understanding of functional consequences of Rho GTPases glucosylation induced by C. difficile toxins and the role of R Ho GTPase in the toxicity of TcdA and TcdB.
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- 2020
The results show that TcdA inhibits Wnt/β-catenin pathway in vivo and demonstrate that this inhibition is likely caused by a Rac1-mediated mechanism.
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- BiologyNaunyn-Schmiedeberg's Archives of Pharmacology
- 2010
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Effects of Clostridium difficile Toxin A on the proteome of colonocytes studied by differential 2D electrophoresis.
- BiologyJournal of proteomics
- 2011
Clostridium difficile Toxin B Causes Epithelial Cell Necrosis through an Autoprocessing-Independent Mechanism
- BiologyPLoS pathogens
- 2012
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Clostridium difficile Toxin Biology.
- BiologyAnnual review of microbiology
- 2017
C. difficile transferase toxin (CDT) is a binary actin-ADP-ribosylating toxin that causes depolymerization of actin, thereby inducing formation of the microtubule-based protrusions.
The role of the globular heads of the C1q receptor in TcdA-induced human colonic epithelial cell apoptosis via a mitochondria-dependent pathway
- Biology, MedicineBMC microbiology
- 2020
A mechanism by which gC1qR plays a crucial role in TcdA-induced apoptosis of human colonic epithelial cells in a mitochondria-dependent manner is supported.
Clostridium difficile Toxin A Undergoes Clathrin-Independent, PACSIN2-Dependent Endocytosis
- Biology, MedicinePLoS pathogens
- 2016
It is shown that TcdA uptake and cellular intoxication is dynamin-dependent but does not involve clathrin- or caveolae-mediated endocytosis, and that TCDA and TcdB utilize distinct endocytic mechanisms to intoxicate host cells.
Time-resolved cellular effects induced by TcdA from Clostridium difficile.
- BiologyRapid communications in mass spectrometry : RCM
- 2014
LC/MS-based proteome analyses and the ICPL approach revealed comprehensive and reproducible proteome date and provided new insights into the cellular effects of clostridial glucosylating toxins (CGT).
References
SHOWING 1-10 OF 36 REFERENCES
Rho protein inactivation induced apoptosis of cultured human endothelial cells.
- BiologyAmerican journal of physiology. Lung cellular and molecular physiology
- 2002
Inhibition of Rho in endothelial cells activates caspase-9- and -3-dependent apoptosis, which can be antagonized by cAMP elevation.
Glucosylation of Rho proteins by Clostridium difficile toxin B
- Biology, ChemistryNature
- 1995
It is reported here that toxin B catalyses the incorporation of up to one mole of glucose per mole of RhoA at the amino acid thre-onine at position 37, and UDP-glucose selectively serves as cosubstrate for the monoglucosylation reaction catalysed by toxin B.
Cellular stability of Rho‐GTPases glucosylated by Clostridium difficile toxin B
- BiologyFEBS letters
- 2006
Clostridium difficile Toxin B Induces Apoptosis in Intestinal Cultured Cells
- Biology, MedicineInfection and Immunity
- 1998
This study dealt with CdB, providing the first evidence that intestinal cells exposed to this toxin exhibit typical features of apoptosis in that a significant proportion of the treated cells displayed nuclear fragmentation and chromatin condensation.
Protective role of HSP72 against Clostridium difficile toxin A-induced intestinal epithelial cell dysfunction.
- Biology, MedicineAmerican journal of physiology. Cell physiology
- 2003
It is concluded that HSP72 may protect intestinal epithelial cells from TxA-mediated damage through several mechanisms, including actin stabilization, mitochondrial protection, and inhibition of apoptosis activation, but not by prevention of RhoA glucosylation.
Mechanism of Clostridium difficile toxin A-induced apoptosis in T84 cells.
- Biology, MedicineThe Journal of infectious diseases
- 2002
In conclusion, toxin A induces apoptosis by a mechanism dependent on inactivation of Rho, activation of caspases 3, 6, 8, and 9 and Bid, and mitochondrial damage followed by cytochrome c release.
Large clostridial cytotoxins.
- Biology, ChemistryReviews of physiology, biochemistry and pharmacology
- 2004
The large clostridial cytotoxins are a family of structurally and functionally related exotoxins from Clostridium difficile (toxins A and B), C. sordellii (lethal and hemorrhagic toxin) and C. novyi…
Inactivation of the small GTPase Rho disrupts cellular attachment and induces adhesion-dependent and adhesion-independent apoptosis
- BiologyOncogene
- 1997
It is found that dsSIN-based expression of C3 or loss of function mutants of Rho could each induce apoptosis and, in RSM, this effect was observed to be adhesion-independent.
Clostridium difficile Toxin A Induces Intestinal Epithelial Cell Apoptosis and Damage: Role of Gln and Ala-Gln in Toxin A Effects
- Biology, MedicineDigestive Diseases and Sciences
- 2005
Both peptides reduced toxin-induced epithelial damage and thus might play an adjunctive role in C. difficile-induced colitis therapy and prevent the inhibition of migration, apoptosis, and the initial drop in transepithelial resistance induced by TxA.
Lethal toxin from Clostridium sordellii induces apoptotic cell death by disruption of mitochondrial homeostasis in HL‐60 cells
- BiologyCellular microbiology
- 2003
Evidence is provided that LT‐IP82‐induced apoptosis is not a consequence of cortical actin disorganization, suggesting that Rac inactivation does not initiate the apoptotic process.