PXD031726

PXD031726 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-17 03:35:04	ID requested
⏵ 1	2022-05-19 11:26:07	announced

Stieglitz F, Gerhard R, H, ö, nig R, Giehl K, Pich A, Mediates RAS-Dependent Necrosis in Epithelial Cells. Int J Mol Sci, 23(8):(2022) [pubmed]

submitter keyword: Clostridioides difficile

C.diff.

TcdB

Phosphoproteomics

Ras

TcdA

Pyknosis

glucosyltransferase independent effect

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

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PRIDE project URI

• PRIDE
  1. PXD031726
     1. Label: PRIDE project
     2. Name: TcdB of Clostridioides difficile mediates necrosis in epithelial cells and is depend on RAS