PXD031726 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | TcdB of Clostridioides difficile mediates necrosis in epithelial cells and is depend on RAS |
Description | A Clostridioides difficile infection (CDI) is the most common nosocomial infection worldwide. The main virulence factors are TcdA and TcdB, which inhibit small Rho-GTPases. Inhibition of small Rho-GTPases leads to the so-called cytopathic effect, a reorganization of the actin cytoskeleton, an impairment of the colon epithelium barrier function, and inflammation. Additionally, TcdB induces a necrotic cell death termed pyknosis in vitro independently from its glucosyltransferas-es characterized by chromatin condensation and ROS production. To understand the underlying mechanism of this pyknotic effect, we conducted a large-scale phosphoproteomic study. We in-cluded the analysis of alterations in the phosphoproteome after treatment with TcdA, that was investigated for the first time. TcdA exhibit no glucosyltransferase-independent effect and was, thus, a good control to elucidate the underlying mechanism of the glucosyltransferase inde-pendent effect of TcdB. We found RAS to be a central upstream regulator for the glucosyltrans-ferase independent effect of TcdB. Inhibition of RAS leads to a 68% reduction in necrosis. Further analysis revealed apolipoprotein C-III (APOC3) as a possible crucial factor of CDI induced in-flammation in vivo. |
HostingRepository | PRIDE |
AnnounceDate | 2022-05-19 |
AnnouncementXML | Submission_2022-05-19_11:26:06.681.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Florian Stieglitz |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-02-17 03:35:04 | ID requested | |
⏵ 1 | 2022-05-19 11:26:07 | announced | |
Publication List
Stieglitz F, Gerhard R, H, รถ, nig R, Giehl K, Pich A, Mediates RAS-Dependent Necrosis in Epithelial Cells. Int J Mol Sci, 23(8):(2022) [pubmed] |
Keyword List
submitter keyword: Clostridioides difficile |
C.diff. |
TcdB |
Phosphoproteomics |
Ras |
TcdA |
Pyknosis |
glucosyltransferase independent effect |
Contact List
Andreas Pich |
contact affiliation | Hannover Medical School - Institute of Toxicology Research Core Unit - Proteomics Carl-Neuberg-Str. 1 30625 Hannover,Germany |
contact email | Pich.Andreas@mh-hannover.de |
lab head | |
Florian Stieglitz |
contact affiliation | MHH - Toxicology |
contact email | Stieglitz.Florian@mh-hannover.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD031726
- Label: PRIDE project
- Name: TcdB of Clostridioides difficile mediates necrosis in epithelial cells and is depend on RAS