Transcriptome profiles of mice intestine and liver upon infection with Salmonella typhimurium (MC71-TT and MC71-DcdtB)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE72046 | GEO | 2016/03/31
SECONDARY ACCESSION(S): PRJNA292810
REPOSITORIES: GEO
Similar Datasets
Project description:Bacterial genotoxins, produced by several Gram-negative bacteria, induce DNA damage in the target cells. While the responses induced in the host cells have been extensively studied in vitro, the role of the genotoxins as effectors during the course of acute and chronic infections remains poorly characterized.To address this issue, we assessed the effects of the Salmonella enterica genotoxin, known as typhoid toxin, in in vivo models of murine chronic infections. Immunocompetent mice were chronically infected with isogenic S. enterica, serovar Typhimurium (S. Typhimurium) strains, encoding either a functional (MC71-TT) or an inactive (MC71-DcdtB) typhoid toxin. Keywords: salmonella typhimurium, bacterial genotoxins, typhoid toxin, chronic infection, mice model Transcriptomic analysis was performed on intestine tissues (colon, jejunum and ileum) and liver collected from 129S6/SvEvTac mice, either uninfected or infected with S. typhimurium MC71 strains (strain MC71-TT, expressing a functional typhoid toxin, and strain MC71-dcdtB, expressing an inactive typhoid toxin) for 60 days
2016-03-31 | E-GEOD-72046 | biostudies-arrayexpress
Project description:Bacterial genotoxins can damage host cells by targeting their chromosomal DNA. Salmonella Typhi the causative pathogen of typhoid fever in humans, secretes an essential genotoxin called typhoid toxin, which can induce cellular senescence. Here we show that typhoid toxin triggers the senescence-associated secretory phenotype (SASP) by disrupting mitochondrial function, including a decrease in mitochondrial DNA (mtDNA) content and a disturbance of redox homeostasis within mitochondria. This disruption causes the release of mtDNA into the cytosol, which activates type I interferon via the cGAS-STING pathway. We also demonstrate that the GCN2-mediated integrated stress response modulates the upregulation of inflammatory components depending on the STING signaling axis. These SASP factors can propagate the senescence effect to CD4 T cells, potentially leading to senescence in these cells. Our research provides a novel insight into how bacterial genotoxins target mitochondria to induce a proinflammatory SASP, which could be a promising therapeutic target for an anti-toxin intervention.
2024-03-30 | GSE247045 | GEO
Project description:Infection with Salmonella enterica serovar Typhi in humans causes the systemic, life-threatening disease typhoid fever. In the laboratory, typhoid fever can be modeled through the inoculation of susceptible mice with Salmonella enterica serovar Typhimurium. The ensuing disease is characterized by systemic dissemination and colonization of many organs, including the liver, spleen and gallbladder. Using this murine model, we previously characterized the interactions between Salmonella Typhimurium and host cells in the gallbladder and showed that this pathogen can successfully invade gallbladder epithelial cells and proliferate. Additionally, we showed that Salmonella Typhimurium can use bile phospholipids to grow at high rates. These abilities are likely important for quick colonization of the gallbladder during typhoid fever and further pathogen dissemination through fecal shedding. To further characterize the interactions between Salmonella and the gallbladder environment we compared the transcriptome of Salmonella cultures grown in LB or physiological murine bile. Our data showed that many genes involved in bacterial central metabolism are affected by bile, with the citric acid cycle being repressed and alternative respiratory systems being activated. Additionally, our study revealed a new aspect of Salmonella interactions with bile through the identification of phoP as a bile-responsive gene. Repression of phoP expression does not involve PhoPQ sensing of a bile component. Due to its critical role in Salmonella virulence, further studies in this area will likely reveal aspects of the interaction between Salmonella and bile that are relevant to disease.
2011-11-10 | GSE33604 | GEO
Project description:Salmonella-related infections outcome are dependent on the complex interaction between environmental factors, bacterial serotype and host genetic factors. Using ENU chemical mutagenesis, we identified a pedigree named Immunity to Typhimurium 14 (Ity14) carrying a mutation in Stat4 (c.1335+5G>A). Here we used a recognized experimental model of systemic Salmonella Typhimurium infection in mice to study the impact of Stat4 mutation on typhoid-like disease. We compare whole-genome transcriptional profiles between wild-type and Ity14 mutant mice to identify common or unique gene expression profiles between these groups.
2014-05-06 | E-MTAB-1931 | biostudies-arrayexpress
Project description:Damage to our genome causes acute senescence in mammalian cells, which undergo growth arrest and release a secretome that elicits cell cycle arrest in bystander cells through the senescence-associated secretory phenotype (SASP). Thus, acute senescence is a powerful tumour suppressor. Salmonella enterica hijacks senescence through its typhoid toxin, which usurps unidentified factors in the stress secretome of senescent cells to mediate intracellular infections. Here, transcriptomics of toxin-induced senescent cells (txSCs) and proteomics of their secretome identified secreted ligands that activate the TGFβ pathway through SMAD transcription factors. The ligand Wnt5a established a self-amplifying positive feedback loop driving TGFβ signalling, which enforced autocrine senescence in txSCs and paracrine senescence in naive bystander cells by activation of DDRs. Wnt5a and GDF15 increased host cell susceptibility to infection. The study reveals how an innate defence against cancer is co-opted by a bacterial pathogen to cause widespread damage and mediate infections.
2023-09-07 | PXD037373 | Pride
Project description:Bacterial pathogens causing systemic disease commonly evolve from organisms associated with localized infections but differ from their close relatives in their ability to overcome mucosal barriers by mechanisms that remain incompletely understood. Here we investigated whether acquisition of a regulatory gene, tviA, contributed to the ability of Salmonella enterica serotype Typhi to disseminate from the intestine to systemic sites of infection during typhoid fever. To study the consequences of acquiring a new regulator by horizontal gene transfer, tviA was introduced into the chromosome of S. enterica serotype Typhimurium, a closely related pathogen causing a localized gastrointestinal infection in immunocompetent individuals. Modulation of gene expression by TviA in serotype Typhi and Typhimurium was determined by profiling and found to be very comparable. Expression of flagellin, a pathogen associated molecular pattern (PAMP), was repressed by TviA when bacteria were grown at osmotic conditions encountered in tissue, but not at higher osmolarity present in the intestinal lumen. TviA-mediated flagellin repression enabled bacteria to evade sentinel functions of human model epithelia and resulted in increased bacterial dissemination to the spleen in a chicken model.
2010-07-07 | GSE20321 | GEO
Project description:Many non-typhoidal serovars of Salmonella such as Salmonella enterica serovar Typhimurium (S. Typhimurium) are the leading cause of food-borne gastroenteritis, resulting in millions of infections each year and sometimes death. Salmonella enterica serovar Typhimurium is the most common non-typhoidal Salmonella strain isolated from patients around the world and is used as a mouse model to study bacterial pathogenesis and host-microbe interactions. Furthermore, S. Typhimurium is an important pathogen in livestock animals including chickens and cattle. S. Typhimurium utilises a multitude of virulence factors to reach and invade host cells and for its intracellular survival. However, little is known about the mechanism of protein synthesis of these virulence factors at the codon level. Here, we performed RNA-seq and ribosome profiling. Ribosome profiling allows the global mapping of translating ribosomes on the transcriptome and therefore provides direct measure of protein synthesis.
2023-04-01 | E-MTAB-8808 | biostudies-arrayexpress
Project description:Salmonella enterica is an important foodborne pathogen that utilizes secreted effector proteins to manipulate host pathways to facilitate survival and dissemination. Different S. enterica serovars cause disease syndromes ranging from self-limited gastroenteritis to typhoid fever and vary in their repertoire of effectors. We leveraged this natural diversity to identify stm2585, here designated sarA (Salmonella anti-inflammatory response activator), as a Salmonella effector secreted primary by the SPI-2 type III secretion system. SarA is necessary and sufficient to induce STAT3 phosphorylation and IL-10 production, contributing to intracellular replication in vitro and bacterial load at systemic sites in mice. These results demonstrate that Salmonella has evolved effector mechanisms for regulating a host anti-inflammatory signaling pathway important in infection, autoimmunity, and cancer.
2018-06-01 | GSE104354 | GEO
Project description:Bacterial transcription factors (TFs) regulate gene expression to adapt to changing environments; when combined, the TF’s regulatory actions comprise transcriptional regulatory networks (TRNs). The chromatin immunoprecipitation (ChIP) assay is the major contemporary method for mapping in vivo protein-DNA interactions in the genome. It enables the genome-wide study of transcription factor binding sites (TFBSs) and gene regulation. Although rapidly accumulating publicly-available ChIP data are a valuable resource for the study of gene regulation, there are no full datasets of key regulators in Salmonella enterica Typhimurium LT2. Here, we present the genome-wide binding for YdcI in the Salmonella enterica Typhimurium LT2.
2021-08-15 | GSE181791 | GEO
Project description:Raghunathan2009 - Genome-scale metabolic
network of Salmonella typhimurium (iRR1083)
This model is described in the article:
Constraint-based analysis of
metabolic capacity of Salmonella typhimurium during
host-pathogen interaction.
Raghunathan A, Reed J, Shin S,
Palsson B, Daefler S.
BMC Syst Biol 2009; 3: 38
Abstract:
BACKGROUND: Infections with Salmonella cause significant
morbidity and mortality worldwide. Replication of Salmonella
typhimurium inside its host cell is a model system for studying
the pathogenesis of intracellular bacterial infections.
Genome-scale modeling of bacterial metabolic networks provides
a powerful tool to identify and analyze pathways required for
successful intracellular replication during host-pathogen
interaction. RESULTS: We have developed and validated a
genome-scale metabolic network of Salmonella typhimurium LT2
(iRR1083). This model accounts for 1,083 genes that encode
proteins catalyzing 1,087 unique metabolic and transport
reactions in the bacterium. We employed flux balance analysis
and in silico gene essentiality analysis to investigate growth
under a wide range of conditions that mimic in vitro and host
cell environments. Gene expression profiling of S. typhimurium
isolated from macrophage cell lines was used to constrain the
model to predict metabolic pathways that are likely to be
operational during infection. CONCLUSION: Our analysis suggests
that there is a robust minimal set of metabolic pathways that
is required for successful replication of Salmonella inside the
host cell. This model also serves as platform for the
integration of high-throughput data. Its computational power
allows identification of networked metabolic pathways and
generation of hypotheses about metabolism during infection,
which might be used for the rational design of novel
antibiotics or vaccine strains.
This model is hosted on
BioModels Database
and identified by:
MODEL1507180058.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2015-07-30 | MODEL1507180058 | BioModels