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The Binary Toxin of Clostridioides difficile Alters the Proteome and Phosphoproteome of HEp-2 Cells

ABSTRACT: Phosphoproteomics Data of laryngeal carcinoma HEp-2 cells treated with CDT over 4h and 8h

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

SUBMITTER: Florian Stieglitz

LAB HEAD: Andreas Pich

PROVIDER: PXD027411 | Pride | 2021-08-25

REPOSITORIES: Pride

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			Action	DRS
	202001222_CDT_Proteom_SPS_inclusion.7z	Other
	20201020_Arvid_CDT_TMT_Phospho_R1_F1_M1.raw	Raw
	20201020_Arvid_CDT_TMT_Phospho_R1_F1_M2.raw	Raw
	20201020_Arvid_CDT_TMT_Phospho_R1_F2_M1.raw	Raw
	20201020_Arvid_CDT_TMT_Phospho_R1_F2_M2.raw	Raw

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Publications

The Binary Toxin of Clostridioides difficile Alters the Proteome and Phosphoproteome of HEp-2 Cells.

Stieglitz Florian F Gerhard Ralf R Pich Andreas A

Frontiers in microbiology 20210914

Clostridioides difficile is a major cause of nosocomial infection worldwide causing antibiotic-associated diarrhea and some cases are leading to pseudomembranous colitis. The main virulence factors are toxin A and toxin B. Hypervirulent strains of C. difficile are linked to higher mortality rates and most of these strains produce additionally the C. difficile binary toxin (CDT) that possesses two subunits, CDTa and CDTb. The latter is responsible for binding and transfer of ...[more]

PMID: 34594315

Similar Datasets

The Binary Toxin of Clostridioides difficile Alters the Proteome and Phosphoproteome of HEp-2 Cells.

Project description:Clostridioides difficile is a major cause of nosocomial infection worldwide causing antibiotic-associated diarrhea and some cases are leading to pseudomembranous colitis. The main virulence factors are toxin A and toxin B. Hypervirulent strains of C. difficile are linked to higher mortality rates and most of these strains produce additionally the C. difficile binary toxin (CDT) that possesses two subunits, CDTa and CDTb. The latter is responsible for binding and transfer of CDTa into the cytoplasm of target cells; CDTa is an ADP ribosyltransferase catalyzing the modification of actin fibers that disturbs the actin vs microtubule balance and induces microtubule-based protrusions of the cell membrane increasing the adherence of C. difficile. The underlying mechanisms remain elusive. Thus, we performed a screening experiment using MS-based proteomics and phosphoproteomics techniques. Epithelial Hep-2 cells were treated with CDTa and CDTb in a multiplexed study for 4 and 8 h. Phosphopeptide enrichment was performed using affinity chromatography with TiO2 and Fe-NTA; for quantification, a TMT-based approach and DDA measurements were used. More than 4,300 proteins and 5,600 phosphosites were identified and quantified at all time points. Although only moderate changes were observed on proteome level, the phosphorylation level of nearly 1,100 phosphosites responded to toxin treatment. The data suggested that CSNK2A1 might act as an effector kinase after treatment with CDT. Additionally, we confirmed ADP-ribosylation on Arg-177 of actin and the kinetic of this modification for the first time.

| S-EPMC8477661 | biostudies-literature

Natural Clostridioides difficile Toxin Immunization in Colonized Infants.

Project description:BackgroundClostridioides (Clostridium) difficile colonization is common among infants. Serological sequelae of infant C. difficile colonization are poorly understood.MethodsIn this prospective cohort study of healthy infants, stools serially collected between ages 1-2 and 9-12 months were tested for non-toxigenic and toxigenic C. difficile (TCD). Cultured isolates underwent whole-genome sequencing. Serum collected at 9-12 months underwent measurement of IgA, IgG, and IgM against TCD toxins A and B and neutralizing antibody (NAb) titers against toxin B. For comparison, antitoxin IgG and NAb were measured in cord blood from 50 mothers unrelated to study infants.ResultsAmong 32 infants, 16 (50%) were colonized with TCD; 12 were first colonized >1 month before serology measurements. A variety of sequence types were identified, and there was evidence of putative in-home (enrolled siblings) and outpatient clinic transmission. Infants first colonized with TCD >1 month prior had significantly greater serum antitoxin IgA and IgG against toxins A (P = .02 for both) and B (P = .009 and .008, respectively) compared with non-TCD-colonized infants, and greater IgG compared with unrelated cord blood (P = .005). Five of 12 (42%) colonized infants had detectable NAb titers compared with zero non-TCD-colonized infants (P = .02). Breastfeeding was not associated with differences in serological measurements.ConclusionsTCD colonization is associated with a humoral immune response against toxins A and B, with evidence of toxin B neutralization in vitro. The extent and duration of protection against CDI later in life afforded by natural C. difficile immunization events require further investigation.

| S-EPMC7201415 | biostudies-literature

Global hepatic transcript data from LRH-1 hep+/+ and LRH-1 hep-/- livers

2014-07-11 | GSE59305 | GEO

Expression analysis of sk-hep-1(sk) cell and sk-hep-1-sh EZH2(sks) cell

Project description:Investigation of EZH2 knocking down on whole genome gene expression level changes in sk-hep-1 compared to sk-hep-1-sh EZH2.

2015-08-13 | GSE68863 | GEO

Global hepatic transcript data from LRH-1 hep+/+ and LRH-1 hep-/- livers

Project description:Transcript data from LRH-1 hep+/+ and LRH-1 hep-/- livers from mice fed ad libitum and sacrificed at 7 am We used microarrays to detail the global programme of gene expression underlying hepatic function in ad libitum fed mice. 17-19-week-old mice were fed ad libitum, sacrificed at 7 am, and livers snap-frozen in liquid nitorgen for RNA extraction and hybridization on Affymetrix microarrays.

2014-07-11 | E-GEOD-59305 | biostudies-arrayexpress

Identification of the different miRNA expression in Hep-12 Cells compared with Hep-11 cells

Project description:To find miRNAs that regulate the stemness of LTICs, we took advantage of the TIC-enriched Hep-12 and the non-tumorigenic Hep-11 cell lines by genome-wide profiling of miRNA expression with miRNA microarray analysis.

2015-09-24 | GSE71004 | GEO

Toxin A-Predominant Pathogenic Clostridioides difficile: A Novel Clinical Phenotype.

Project description:BACKGROUND:Most Clostridioides difficile toxinogenic strains produce both toxins A and B (A+B+), but toxin A-negative, toxin B-positive (A-B+) variants also cause disease. We report the identification of a series of pathogenic clinical C. difficile isolates that produce high amounts of toxin A with low or nondetectable toxin B. METHODS:An ultrasensitive, quantitative immunoassay was used to measure toxins A and B in stool samples from 187 C. difficile infection (CDI) patients and 44 carriers. Isolates were cultured and assessed for in vitro toxin production and in vivo phenotypes (mouse CDI model). RESULTS:There were 7 CDI patients and 6 carriers who had stools with detectable toxin A (TcdA, range 23-17 422 pg/mL; 5.6% of samples overall) but toxin B (TcdB) below the clinical detection limit (<20 pg/mL; median TcdA:B ratio 17.93). Concentrations of toxin A far exceeded B in in vitro cultures of all 12 recovered isolates (median TcdA:B ratio 26). Of 8 toxin A>>B isolates tested in mice, 4 caused diarrhea, and 3 of those 4 caused lethal disease. Ribotyping demonstrated strain diversity. TcdA-predominant samples were also identified at 2 other centers, with similar frequencies (7.5% and 6.8%). CONCLUSIONS:We report the discovery of clinical pathogenic C. difficile strains that produce high levels of toxin A but minimal or no toxin B. This pattern of toxin production is not rare (>5% of isolates) and is consistently observed in vitro and in vivo in humans and mice. Our study highlights the significance of toxin A in human CDI pathogenesis and has important implications for CDI diagnosis, treatment, and vaccine development.

| S-EPMC7286367 | biostudies-literature

A Clostridioides difficile endolysin modulates toxin secretion without cell lysis

Project description: Not available

| S-EPMC11344133 | biostudies-literature

Clostridioides difficile

Project description:Comparison of the expression profiles of 630E strain after 4h and 10h of growth

| PRJNA142595 | ENA

TcdB of Clostridioides difficile mediates necrosis in epithelial cells and is depend on RAS

Project 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.

2022-05-19 | PXD031726 | Pride