Similar Datasets
Project description:The microarray data provided here belong to a study that describes two different Shiga toxin (Stx) induced models of hemolytic uremic syndrome (HUS) in mice. Although several rodent models of HUS were published, it still remains difficult to reproduce all clinical features of human HUS. Here, two different Stx2 regimes combined with volume resuscitation were tested in C57BL/6J wild type mice. Animals were euthanized because of kidney injury after 3 or 7 days respectively. Kidneys were removed for histological evaluation and RNA extraction. Kidney injury was confirmed histologically and by laboratory parameters in plasma. Data for the respective vehicle treated groups are also provided here.
2017-10-01 | GSE99229 | GEO
Project description:Intestinal tissue responses to protein synthesis inhibition by Shiga toxin are complex. Organoid models allow for an unprecedented examination of human tissue responses to a deadly Shiga toxin.
2020-02-01 | GSE144633 | GEO
Project description:phi 1720a shiga toxin prophage
| PRJEB102386 | ENA
Project description:Shiga-toxin producing Enterotoxigenic Escherichia coli
| PRJEB25657 | ENA
Project description:Changes in endothelial phenotype induced by E. coli-derived Shiga toxins (Stx) are believed to play a critical role in the pathogenesis of hemolytic uremic syndrome. Stx inactivate host ribosomes, but also alter gene expression at concentrations that minimally affect global protein synthesis. The effect of Stx on the gene expression profile of human microvascular endothelial cells was examined using the Affymetrix HG-U133A platform. Data were processed using 13 different methods and revealed 369 unique differentially expressed genes, 318 of which were up-regulated and 51 of which were down-regulated. These studies implicated activation of the CXCR4/CXCR7/SDF-1 chemokine pathway in Stx-mediated pathogenesis. Primary human dermal microvascular endothelial cells were treated with vehicle or Shiga toxin (10 fM, 24 h, n = 6) and changes in steady-state mRNA levels were determined by hybridization to Affymetrix HG-U133A arrays
2011-10-10 | E-GEOD-32710 | biostudies-arrayexpress
Project description:Infection with enterohemorrhagic E. coli (EHEC) causes severe changes in the brain leading to angiopathy, encephalopathy and microglial activation. In this study, we investigated the role of tumour necrosis factor alpha (TNF-α) for microglial activation and brain pathology using a preclinical mouse model of EHEC infection. LC–MS/MS proteomics of mice injected with a combination of Shiga toxin (Stx) and lipopolysaccharide (LPS) revealed extensive alterations of the brain proteome, in particular enrichment of pathways involved in complement activation and coagulation cascades. Inhibition of TNF-α by the drug Etanercept strongly mitigated these changes, particularly within the complement pathway, suggesting TNF-α-dependent vasodilation and endothelial injury. Analysis of microglial populations using a novel human-in-the-loop deep learning algorithm for the segmentation of microscopic imaging data indicated specific morphological changes, which were reduced to healthy condition after inhibition of TNF-α. Moreover, the Stx/LPS-mediated angiopathy was significantly attenuated by inhibition of TNF-α. Overall, our findings elucidate the critical role of TNF-α in EHEC-induced brain pathology and highlight a potential therapeutic target for mitigating neuroinflammation, microglial activation and injury associated with EHEC infection.
2025-02-18 | PXD052925 | Pride
Project description:Tissue responses to Shiga toxin in human intestinal organoids
| PRJNA604235 | ENA
Project description:Enterohaemorrhagic E. coli is significant human pathogen that causes disease ranging from haemorrhagic colitis to haemolytic uremic syndrome. The later can lead to potentially fatal renal failure and is caused by the release of Shiga toxins that are encoded within lambdoid bacteriophages. The toxins are encoded within the late transcript of the phage and are regulated by anti-termination of the PR’ late promoter during lytic induction of the phage. During lysogeny, the late transcript is prematurely terminated at tR’ immediately downstream of PR’, generating a short RNA that is a by-product of anti-termination regulation. We demonstrate that this short transcript binds the small RNA chaperone Hfq, and is processed into a stable 74 nt regulatory small RNA that we have termed, StxS. StxS activates expression of the general stress response sigma factor, RpoS, through direct interactions with an activating seed sequence within the 5’ UTR. StxS represses expression of Shiga toxin 1 and activation of RpoS promotes high cell density growth under nutrient limiting conditions. Many phages utilise anti-termination to regulate the lytic/lysogenic switch and our results demonstrate that short RNAs generated as a by-product of this regulation can acquire regulatory small RNA features and modulate host fitness.
2020-09-16 | GSE143631 | GEO
Project description:Shiga toxin type 2 (Stx2) is the main virulence factor produced by Stx-producing Escherichia coli (STEC) responsible for hemorrhagic colitis and the life-threatening sequela hemolytic uremic syndrome.
2022-11-21 | PXD038256 |
Project description:The retrograde transport inhibitor Retro-2 has a protective effect on cells and in mice against Shiga-like toxins and ricin. Retro-2 causes toxin accumulation in early endosomes, and the relocalization of the Golgi SNARE protein syntaxin-5 to the endoplasmic reticulum. The molecular mechanisms by which this is achieved remain unknown. Here, we show that Retro-2 targets the endoplasmic reticulum exit site component Sec16A, affecting anterograde transport of syntaxin-5 from the endoplasmic reticulum to the Golgi. The formation of canonical SNARE complexes involving syntaxin-5 is not affected in Retro-2-treated cells. In contrast, the interaction of syntaxin-5 with a newly discovered binding partner, the retrograde trafficking chaperone GPP130, is abolished, and we show that GPP130 must indeed bind to syntaxin-5 to drive Shiga toxin transport from endosomes to the Golgi. We thereby identify Sec16A as a druggable target, and provide evidence for a non-SNARE function for syntaxin-5 in interaction with the retrograde cycling protein GPP130. a) Clickable Retro-2 pulldown. To identify protein target of Retro-2.1, providing the first steps to explain effects of Retro-2 on inhibition of STxB retrograde trafficking from endosomes to Golgi. b) GFP-STX5 pulldown. To find interactors of STX5, to build a hypothesis to explain the affect of Retro-2-inhibited anterograde trafficking of STX5 to Golgi, which in turn inhibits STxB retrograde transport from endosomes to Golgi. c) GFP-Sec16A pulldown. The aim of this proteomics assay is to show the effects of Retro-2 on the Sec16A interactome. Results show the differential effects of Retro-2 treatment on the Sec16A interactome, giving insight into the mechanism by which Retro-2, via Sec16A, specifically affects the anterograde trafficking of Syntaxin-5.
2020-02-24 | PXD015642 | Pride