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Flagellar regulation in enterotoxigenic E. coli modulates innate immune activation

ABSTRACT: Human jejunal organoid monolayers were used as a model for epithelial innate immune responses to infection with different strains of the diarrheal pathogen enterotoxigenic E. coli (ETEC). Our hypothesis is that strain H10407 harbors mutations that facilitate activation of epithelial inflammatory responses.

ORGANISM(S): Homo sapiens

PROVIDER: GSE331118 | GEO | 2026/05/20

REPOSITORIES: GEO

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Molecular and immunological interrogation of a live-attenuated enterotoxigenic Escherichia coli vaccine highlights features unique to wild type infection

Project description:Enterotoxigenic Escherichia coli (ETEC) infections are a common cause of diarrheal illness in low- and middle-income countries. The live-attenuated ACE527 vaccine, adjuvanted with double mutant LT (dmLT), affords clear but partial protection against ETEC challenge inhuman volunteers. Comparatively, initial wild-type ETEC challenge completely protects against severe diarrhea on homologous re-challenge...To investigate molecular determinants of protection, vaccine antigen content was compared to wild-type ETEC, and proteome microarrays were used to assess immune responses following vaccination and ETEC challenge... Although molecular interrogation of the vaccine confirmed expression of targeted canonical antigens, relative to wild-type ETEC, vaccine strains were deficient in production of flagellar antigens, immotile, and lacked production of the EtpA adhesin. Similarly, vaccination ± dmLT elicited responses to targeted canonical antigens, but relative to wild-type challenge, vaccine responses to some potentially protective non-canonical antigens including EtpA were diminished or absent...These studies highlight important differences in vaccine and wild-type ETEC antigen content and call attention to distinct immunologic signatures that could inform investigation of correlates of protection, and guide vaccine antigen selection for these pathogens of global importance.

2019-07-25 | GSE134792 | GEO

The MAIT cell response to controlled oral enterotoxigenic E. coli challenge

Project description:Mucosa-associated invariant T (MAIT) cells recognize conserved microbial antigens presented by the non-polymorphic MR1 molecules and play important roles in barrier immunity. Enterotoxigenic E. coli (ETEC) is a major cause of diarrheal disease especially among children in lower-income countries. Here we investigate the potential role of MAIT cells in ETEC infection using samples from a human experimental ETEC challenge study. MAIT cells were activated with elevated function and proliferation in blood on day 7 after challenge, reflected both at protein and transcript levels, a pattern most evident among individuals who developed mild to severe diarrhea (MSD). The MSD-positive group had elevated expression of CCR9 and α4β7 on MAIT cells and experienced expansion of the peripheral MAIT cell pool at day 28 after challenge. Finally, the size of the MAIT cell pool correlated with MSD disease severity score. These findings indicate that MAIT cells respond to ETEC infection in a way associated with the development of symptomatic disease.

2025-05-20 | GSE276378 | GEO

Transcriptomic Analysis of the Host Response and Innate Resilience to Enterotoxigenic Escherichia coli Infection in Humans

Project description:Enterotoxigenic Escherichia coli (ETEC) is a globally prevalent cause of diarrhea. We report the first gene expression analysis of the human host response to experimental challenge with ETEC.

2017-02-22 | GSE95104 | GEO

Characterization of the genes that were regulated by infection with enterotoxigenic E. coli (ETEC)

Project description:In the present study, we investigated the pathogenicity of infection with enterotoxigenic E. coli (ETEC) using Caenorhabditis elegans as a model animal. The lifespan of the adult C. elegans infeted with ETEC was significantly longer than that of uninfected animals (control). Transcriptional profiling comparing infected- and uninfected animals suggested that genes related to the insulin-like peptide were upregulated by infection with ETEC.

2023-11-11 | GSE247108 | GEO

Intestinal proteomic response to oral challenge of enterotoxigenic Escherichia coli in weaned pigs

Project description:Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhoea in children in resource-limited countries and of travellers diarrhoea. The ileal proteomics change after ETEC challenge is less characterised. Here in this study changes of ileal proteins post ETEC challenge in weaned pigs are studied. In total, 5151 ileal proteins were successfully annotated and 9 proteins had significantly different abundance between the ETEC and CON pigs.

2022-04-01 | PXD028066 | Pride

Degradation of the intestinal mucus layer by the ETEC protease EatA is species specific determined by the structure of the MUC2 mucin

Project description:Enterotoxigenic Escherichia coli (ETEC) infections are a leading cause of diarrheal illness, responsible for an estimated 100,000 deaths annually. ETEC pathogenesis is driven by various virulence factors, including toxins, adhesins, and noncanonical factors such as the protease EatA. The first line of host defense against intestinal pathogenic bacterial infections is the protective intestinal mucus layer. Here, we demonstrate the mechanism by which EatA facilitates access to the epithelial cell surface by degrading the core mucus component MUC2, thereby aiding to the infection. We identify the specific cleavage site region localized at the C-terminal of MUC2. EatA's protease activity depends on the interaction between two distinct domains, which are uniquely spaced in human MUC2, contributing to species specificity. This was confirmed using a novel chimeric mouse model solely expressing human MUC2, which allowed us to study the role of the mucus layer in the infection of human intestinal pathogens. These findings highlight how ETEC has adapted to specifically degrade the mucus layer of its human host.

2026-01-19 | PXD068558 | Pride

MeDIP-chip for porcine intestinal epithelial cells with ETEC F4ab/ac infection

Project description:To better understand the molecular effects of Enterotoxigenic Escherichia coli (ETEC) F4ab/ac infection, we performed a genome-wide comparison of the changes in DNA methylation in ETEC F4ab/ac infected porcine intestinal epithelial cells. Our data provides further insight into the epigenetic alterations of ETEC F4ab/ac infected porcine intestinal epithelial cells and may advance the identification of biomarkers and drug targets for predicting susceptibility to and controlling ETEC F4ab/ac induced diarrhea.

2020-04-06 | GSE143661 | GEO

Proteomics of Diverse Clonal Groups of Enterotoxigenic Escherichia coli Underline Variations in Surface Antigens and Similarities in Metabolism

Project description:Enterotoxigenic Escherichia coli (ETEC) is an important cause of diarrhoea, a pervasive disease in low- and middle-income countries that affects mostly young children and visiting travellers. Substantial diversity exists among ETEC isolates, hindering development of effective preventive means. To investigate how ETEC genomic variation is reflected at expressed proteome level, we applied label-free quantitative proteomics to 7 human ETEC strains representing 5 epidemiologically important lineages. We further determined the protein profile of the non-pathogenic E. coli B strain BL21 to discriminate metabolic features specific for ETEC. The analysis yielded a dataset of 2,894 proteins, of which 1,777 were present in all strains. Each ETEC strain displayed on average 27 (±10) proteins with known or putative links to virulence, both plasmid- and chromosomally-encoded, and a number of strain-specific isoforms participating in the biosynthesis of surface antigens. Statistical comparison of relative protein levels between the ETEC strains and BL21 revealed several proteins with significantly increased amounts only in BL21, including enzymes of arginine biosynthesis and metabolism of melibiose, galactitol and gluconate. ETEC strains displayed consistently increased levels of proteins that were functional in iron acquisition, maltose metabolism, and acid resistance. These results suggest that specific metabolic functions are shared among ETEC isolates.

2017-12-06 | PXD005259 | Pride

Improving Genome Annotation of Enterotoxigenic Escherichia coli TW10598 by a Label-Free Quantitative MS/MS Approach

Project description:The most commonly used genome annotation processes are to a great extent based on computational methods. However, those can only predict genes that have been described earlier or that have sequence signatures indicative of a gene function. We reported a synonymous proteogenomic approach for experimentally improving microbial genome annotation based on label-free quantitative MS/MS. The approach was exemplified by analysis of cell extracts from in vitro cultured enterotoxigenic Escherichia coli (ETEC) strain TW10598, as part of an effort to create a new reference ETEC genome sequence. The proteomic analysis yielded identification of 2,060 proteins, out of which 274 proteins were originally described as hypothetical. For 84% of the identified proteins we have provided description of their relative quantitative levels, among others, for 20 abundantly expressed ETEC virulence factors. Proteogenomic mapping supported the existence of four protein-coding genes that had not been annotated, and led to correction of translation start positions of another nine.

2015-09-15 | PXD002473 | Pride

E. coli strain E24377A

Project description:This SuperSeries is composed of the following subset Series: GSE31804: Expression data of enterotoxigenic (ETEC) isolate E24377A GSE31805: Global transcriptomics of enterotoxigenic E. coli strain E24377A Refer to individual Series

2012-03-01 | E-GEOD-31806 | biostudies-arrayexpress

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