Phosphatase-independent suppression of mucosal inflammation and disease progression by Salmonella SopB
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE300992 | GEO | 2026/06/21
REPOSITORIES: GEO
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Project description:Salmonella enterica serovar Typhimurium is a rod-shaped Gram-negative bacterium. It is a leading cause of gastroenteritis and public health problem. In the environment, it interacts with protozoa, particular amoeba, however the interactions between Salmonella and these eukaryotic microbes have not been addressed in detail. We and others recently described that S. Typhimurium is able to survive in the model amoeba Dictyostelium discoideum requiring the Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2, respectively)-encoded type three secretion systems (T3SSs). In this work, we investigated the role of two particular effector proteins, SopB and SifA that are secreted by either one of the T3SSs. SopB and SifA are involved in the remodelling of the intracellular compartment that contains Salmonella (Salmonella-containing vacuole, SCV) in other cellular models. We combined genetic and proteomics analysis to investigate the roles of SopB and SifA during infections of D. discoideum. We identified over 1,000 proteins per sample performing proteomics on fractions enriched in SCVs from amoeba cells infected with wild-type, sopB or sifA S. Typhimurium. Among them, we observed several Rho GTPases, guanine nucleotide exchange factors and motor proteins. Finally, we decided to evaluate if the changes observed in the proteome from the SCV of wild-type and mutants affect the intracellular survival of S. Typhimurium. These finding suggest that Salmonella exploits this route to survive intracellularly, a process that requires SopB and/or SifA effectors. To our knowledge this is the first proteomic description of the Salmonella intracellular compartment in D. discoideum.
2020-09-23 | PXD014955 | Pride
Project description:Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) manipulates cellular processes through the translocation of effector molecules into the host cell cytosol. Using a recently established neonatal S. Typhimurium infection model, we provide functional insights into how Salmonella outer protein B (SopB) suppresses early mucosal tissue inflammation and prolongs host survival. Mechanistically, SopB prevents a disintegrin and metalloprotease 17 (ADAM17) activation, plasma membrane translocation and the release of membrane-bound TNFa from enterocytes and reduces epithelial secretion of IL-18 via mTOR-controlled secretory autophagy. This abolishes the early epithelial transcriptional response and reduces immune cell recruitment and programmed cell death-mediated mucosal barrier disruption delaying disease progression. The immunosuppressive effect of SopB is independent of the C-terminally encoded phosphatidylinositol phosphatase and phosphotransferase activity but requires an intact N-terminal domain. Thus, SopB suppresses the early, post-transcriptional regulation of epithelial cytokine release in an inositol phosphatase-independent manner likely promoting pathogen transmission.
2026-04-06 | GSE326693 | GEO
Project description:We identified a differential enrichment of TET-medaited 5hmC in human enterocyte (Caco2BBE1 cells) upon infection with salmonella typhimurium. Genes enriched with 5hmC are involved in Wnt and Notch signaling pathways.
2023-09-04 | GSE241789 | GEO
Project description:Subversion of the host cytoskeleton is a critical virulence mechanism used by a variety of intracellular bacterial pathogens during their infectious life cycles. Growing evidence suggests that the tactics employed by pathogens are surprisingly diverse. Using proteomic and biochemical methods, we demonstrate that the S. Tm type III effector protein SopB potently interacts specifically with host cell IFs vimentin. After host cell entry, Salmonella replicates in Salmonella containing vacuoles (SCVs), which accumulate a dense meshwork of vimentin through the Salmonella SPI-1 type III secretion effector SopB. We also demonstrate an important role for SopB-vimentin interaction, in the cellular responses including pro-inflammatory cytokine production induced by Salmonella. Vimentin interacts with the N-terminus of the S. Tm T3SS effector protein SopB. Vimentin and its interaction with SopB are dispensable for S. Tm invasion, but are required for stable formation of SCVs which are essential for bacteria replication. Moreover, SopB lacking of N-terminus cdc42-binding domain loses the interaction with vimentin, suggesting that the small GTPase is critical in SopB triggered vimentin recruitment to form integrative SCVs. These findings establish that SCVs integrity of the bacterium specifically requires intermediate filaments vimentin, which is a prerequisite for highly efficient S. Tm replication.
2023-03-11 | PXD028785 | Pride
Project description:Longitudinal analysis of Salmonella typhimurium mRNA from superspeader mouse cecal content and stool compared to in vitro Salmonella typhimurium mRNA.
2023-03-22 | GSE207764 | GEO
Project description:RNA from in vitro grown Salmonella typhimurium is compared with RNA extracted from Salmonella typhimurium from infected chick caecums using a common DNA reference. Keywords: Disease state analysis, infected versus uninfected, common reference
2008-02-12 | GSE10337 | GEO
Project description:gd T cells have an important yet incompletely defined role in inflammation associated with a variety of infectious and autoimmune conditions. To better understand the precise roles of gd T cells relative to ab T cells in a specific infection, we utilized Salmonella Enterica Serovar Typhimurium (S. typhimurium) infection in cattle as it is a leading cause of disease in cattle and closely approximates S. typhimurium-induced enterocolitis in humans. To best represent phenotype and gene expression changes occurring in the gut mucosa early in S. typhimurium infection, gd and ab T cells were collected directly from the mesenteric lymphatic ducts and analyzed by FACS or immediately sorted and processed for microarray analysis. Gene expression profiles were compared at intervals during infection within T cell subsets. The majority of gene expression changes in both subsets occurred 48 hours after infection. In response to S. typhimurium infection there was an increase in expression of several genes in gd T cells which were indicative of activation, proliferation and innate function, whereas in ab T cells gene expression changes suggested a lack of S. typhimurium-specific response. This work represents the first focus on gene expression trends in tissue-derived T lymphocytes in an in vivo model that is highly relevant to human S. typhimurium-induced enterocolitis. Keywords: Comparison of ab and gd T cells in bovine lymphatic fluid time course after salmonella or mock infection
2007-06-30 | GSE3439 | GEO
Project description:Salmonella enterica Serovar Typhimurium (S. Typhimurium) causes enterocolitis in humans and calves characterized by diarrhea and polymorphonuclear cell (PMN) influx to the intestinal mucosa. The Salmonella Type III Secretion System encoded at Pathogenicity Island I (SPI-1) translocates the Salmonella effector proteins SipA, SopA, SopB, SopD, and SopE2 into the host epithelial cell cytoplasm. These five effector proteins act in concert to induce fluid secretion and transcription of C-X-C chemokines, which serve to recruit PMNs to the intestine. While the individual molecular interactions of these Salmonella proteins with cultured host cells have been extensively characterized, their combined role in the generation of fluid secretion and inflammation is less well understood. A bovine ligated ileal loop model was used in conjunction with a custom bovine microarray to determine intestinal response to acute S. Typhimurium infection in the calf. Gene expression responses to both wild type S. Typhimurium a delta sipA, sopABDE2 mutant were measured at seven times during the initial 12 hours of infection. Microarray analysis confirmed increased expression of genes encoding proteins previously associated with immune response to Salmonella spp. infection. Gene expression changes were mapped to molecular interaction pathways and changes in expression of mechanistic genes, which are defined as perturbed genes identified by Bayesian genetic network modeling, were strongly involved in the mechanisms of the host immune response. In addition to correctly identifying known effects of wild type S. Typhimurium on host (bovine) gene expression, Bayesian genetic network modeling identified novel effects of S. Typhimurium on several molecular interaction pathways. Novel effects impacted gene regulation in the following pathways: adipocytokine signaling, insulin signaling, complement and coagulation cascades, axon guidance, gap junction, neuroactive ligand-receptor interaction, long-term depression, long-term potentiation, melanogenesis, and natural killer cell mediated cytotoxicity. Known effects were observed in the following pathways: regulation of actin cytoskeleton, apoptosis, cytokine-cytokine receptor interaction, cell adhesion molecules (CAMs), MAPK signaling, calcium signaling, Jak-STAT signaling, leukocyte transendothelial migration, adherens junction, tight junction, and ECM-receptor interactions, phosphatidylinositol signaling system, and antigen processing and presentation. Quantitative real-time PCR was used to verify the expression of some of these mechanistic genes.
2012-01-10 | GSE13847 | GEO
Project description:InvF ChIP-chip on Salmonella enterica serovar Typhimurium SL1344 using anti-Myc antibody against strain with chromosomally 9Myc-tagged InvF (IP samples) and wildtype strain (mock IP samples) Salmonella enterica serovar Typhimurium causes a range of diseases from self-limiting gastroenteritis to life-threatening systemic infections. Its complex infection process is initiated by the invasion of the intestinal epithelial monolayer by means of a type three secretion system. InvF is one of the key regulators governing the invasion of epithelial cells. By mapping the InvF regulon, i.e. locating its direct target genes, the gene network underlying invasion can be further examined, including identifying possible new effector-encoding genes. In order to map the InvF regulon, we performed chromatin immunoprecipitation combined with tiling microarray analysis (ChIP-chip) and compared expression of the identified target genes in an invF mutant and a wildtype strain. In addition, the promoter regions of these target genes were searched for the presence of an InvF recognition site. Finally, a query-driven biclustering method, combined with a microarray compendium containing publically available S. Typhimurium gene expression data, was applied as an in silico validation technique for functional relatedness between newly identified target genes and known invasion genes. As expected, under invasion inducing conditions, InvF activates the expression of invasion chaperone encoding sicA and the effector-encoding genes sopB, sopE, sopE2 and sopA by binding their promoter region. Newly identified InvF targets are steB, encoding a secreted effector, and STM1239. The presence of an InvF recognition site in the promoter regions of these target genes further supports this observation. In addition, the query-driven biclustering method revealed similarities in expression profiles between STM1239 and known InvF regulated invasion genes over a range of experimental conditions. In conclusion, we here deliver the first evidence for direct binding of InvF to the promoter regions of sopA and sopE2, and associate genes encoding a secreted effector (steB) and a putative novel effector (STM1239) with the Salmonella invasion regulator InvF. Three IP samples (from three biological replicates using anti-Myc antibody against Salmonella Typhimurium SL1344 strain encoding chromosomally 9Myc-tagged InvF) and three control mock IP samples (from three biological replicates using anti-Myc antibody against Salmonella Typhimurium SL1344 wildtype strain) were labeled with Cy5 and hybridized against a common genomic DNA reference, labeled with Cy3, on 6 S. Typhimurium LT2 whole genome tiling arrays
2013-09-01 | E-GEOD-24062 | biostudies-arrayexpress
Project description:We report the genome-wide analysis from chromatin immunoprecipitated DNA (ChIP-sequencing) of the DNA binding pattern of ParBF (SopB) of plasmid F. This study, performed in E. coli and Salmonella typhimurium, investigates the impact of DNA supercoiling on ParBF DNA binding profiles in vivo. We found that variation in DNA supercoiling does not significantly affect the ParB DNA binding profiles even on linear DNA.
2024-07-01 | GSE256357 | GEO