CDK1-formin signal confers microvillar effacement by an attaching and effacing (A/E) pathogen
Ontology highlight
ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE142507 | GEO | 2020/11/11
REPOSITORIES: GEO
Similar Datasets
Project description:CDK1-formin signal confers microvillar effacement by an attaching and effacing (A/E) pathogen
| PRJNA597224 | ENA
Project description:In a variety of organisms, including mammals, caloric restriction improves metabolic status and lowers the incidence of chronic-degenerative diseases, ultimately leading to increased lifespan. Here we show that knockout mice for Eps8, a regulator of actin dynamics, display reduced bodyweight, partial resistance to age- or diet-induced obesity, and overall improved metabolic status. We present evidence that these phenotypes, which are associated to increased lifespan in the Eps8 null mice, are due to caloric restriction. This, in turn, is caused by reduced intestinal fat absorption, due to altered morphogenesis of microvilli in intestinal enterocytes. In the nematode, genetic removal of Eps8, causes a microvillar phenotype, indistinguishable from that observed in mice, which leads to early larval lethality. By exploiting the nematode model system, we demonstrate here that the actin bundling activity of Eps8 is indispensable for viability and proper intestinal morphogenesis. This result links a precise molecular function of Eps8 to proper microvillar morphogenesis, and therefore to the phenotype of Eps8-null mice. Our results implicate actin dynamics in individual variations in bodyweight, metabolic status and longevity. cDNA expression profiling of liver of 4 mutant EPS8 -/- animals versus pool of 4 wt animals. 8 hybridisation including 4 dye swap experiments
2010-03-09 | E-GEOD-14454 | biostudies-arrayexpress
Project description:VS94 gene expression at different time-points in SAPI medium in absence and presence of AI-2 was studied. Autoinducer-2 (AI-2) is produced by many species of bacteria, including various commensal bacteria and is involved in inter-species communication. Since, pathogens encounter AI-2 once they enter the human gastro-intestinal tract; we studied the effects of presence of AI-2 on various phenotypes associated with infection and colonization of enterohemorrhagic Escherichia coli (EHEC) namely, chemotaxis, motility and attachment to HeLa cells. AI-2 attracted EHEC when observed in agarose plug assays and also increased EHEC motility by 1.44-fold. AI-2 also increased EHEC attachment to HeLa cells by 1.6-fold; hence, suggesting that exposure to AI-2 inside the gastro-intestinal tract can play an important role in EHEC colonization. We then investigated the global effects of AI-2 on EHEC gene expression using DNA microarrays at various time-points. We found that AI-2 controls virulence gene expression and several other groups of genes (flagellar genes, iron related genes, biofilm genes etc.) associated with virulence in a time-dependent manner. Hence, through these studies we have shown that AI-2 may be a key component in EHEC infection of human gastro-intestinal tract. Keywords: Time course
2008-03-21 | GSE9388 | GEO
Project description:Enteropathogenic Escherichia coli and enterohemorrhagic E. coli are diarrheagenic bacterial human pathogens that cause severe gastroenteritis. These enteric pathotypes, together with the mouse pathogen Citrobacter rodentium, belong to the family of attaching and effacing pathogens that form a distinctive histological lesion in the intestinal epithelium. The virulence of these bacteria depends on a type III secretion system (T3SS), which mediates the translocation of effector proteins from the bacterial cytosol into the infected cells. The core architecture of the T3SS consists of a multi-ring basal body embedded in the bacterial membranes, a periplasmic inner rod, a transmembrane export apparatus in the inner membrane, and cytosolic components including an ATPase complex and the C-ring. In addition, two distinct hollow appendages are assembled on the extracellular face of the basal body creating a channel for protein secretion: an approximately 23 nm needle, and a filament that extends up to 600 nm. This filamentous structure allows these pathogens to get through the host cells mucus barrier. Upon contact with the target cell, a translocation pore is assembled in the host membrane through which the effector proteins are injected. Assembly of the T3SS is strictly regulated to ensure proper timing of substrate secretion. The different type III substrates coexist in the bacterial cytoplasm, and their hierarchical secretion is determined by specialized chaperones in coordination with two molecular switches and the so-called sorting platform. In this review, we present recent advances in the understanding of the T3SS in attaching and effacing pathogens.
| S-EPMC5073101 | biostudies-literature
Project description:EHEC is a food-borne pathogen that colonizes human GI tract and leads to infection. To understand the process of colonization and to decipher if any factors secreted by intestinal epithelial cells help EHEC during the infection process, we studied expression of EHEC virulence gene expression when exposed to intestinal epithelial cell conditioned medium. In our study, we observed that exposure to epithelial cell conditioned medium for 1 h and 3 h increases expression of 32 out of 41 EHEC LEE virulence genes. In addition, expression of the shiga toxin 1 (Stx1) gene is up-regulated at 1 h of exposure. Also, 17 genes encoded by prophage 933W, including those for Stx2, are also upregulated at both time-points. The increase in 933W prophage expression is mirrored by a 2.7-fold increase in intracellular Stx2 phage titers. Consistent with the increase in virulence gene expression, we observed a 5-fold increase in EHEC attachment to epithelial cells when exposed to conditioned medium, suggesting that EHEC utilizes host cell molecules to increase virulence and infectivity. The molecule(s) responsible for increased EHEC virulence is heat-sensitive as heating the conditioned medium to 95oC abolishes the increase in attachment to epithelial cells. A similar decrease was observed when the conditioned medium was treated with proteinase-K to degrade the proteins. The secreted molecule(s) was found to be larger than 3 kDa and strongly suggests that the HCT-8 secreted molecule that increases EHEC virulence and colonization is a protein-based molecule. Affymetrix E. coli Genome 2.0 Arrays were used to determine the changes in EHEC virulence gene expression on exposure to intestinal epithelial cell-secreted factors (through growth in conditioned medium).
2012-10-04 | GSE22285 | GEO
Project description:In a variety of organisms, including mammals, caloric restriction improves metabolic status and lowers the incidence of chronic-degenerative diseases, ultimately leading to increased lifespan. Here we show that knockout mice for Eps8, a regulator of actin dynamics, display reduced bodyweight, partial resistance to age- or diet-induced obesity, and overall improved metabolic status. We present evidence that these phenotypes, which are associated to increased lifespan in the Eps8 null mice, are due to caloric restriction. This, in turn, is caused by reduced intestinal fat absorption, due to altered morphogenesis of microvilli in intestinal enterocytes. In the nematode, genetic removal of Eps8, causes a microvillar phenotype, indistinguishable from that observed in mice, which leads to early larval lethality. By exploiting the nematode model system, we demonstrate here that the actin bundling activity of Eps8 is indispensable for viability and proper intestinal morphogenesis. This result links a precise molecular function of Eps8 to proper microvillar morphogenesis, and therefore to the phenotype of Eps8-null mice. Our results implicate actin dynamics in individual variations in bodyweight, metabolic status and longevity.
2010-03-09 | GSE14454 | GEO
Project description:EHEC is a food-borne pathogen that colonizes human GI tract and leads to infection. To understand the process of colonization and to decipher if any factors secreted by intestinal epithelial cells help EHEC during the infection process, we studied expression of EHEC virulence gene expression when exposed to intestinal epithelial cell conditioned medium. In our study, we observed that exposure to epithelial cell conditioned medium for 1 h and 3 h increases expression of 32 out of 41 EHEC LEE virulence genes. In addition, expression of the shiga toxin 1 (Stx1) gene is up-regulated at 1 h of exposure. Also, 17 genes encoded by prophage 933W, including those for Stx2, are also upregulated at both time-points. The increase in 933W prophage expression is mirrored by a 2.7-fold increase in intracellular Stx2 phage titers. Consistent with the increase in virulence gene expression, we observed a 5-fold increase in EHEC attachment to epithelial cells when exposed to conditioned medium, suggesting that EHEC utilizes host cell molecules to increase virulence and infectivity. The molecule(s) responsible for increased EHEC virulence is heat-sensitive as heating the conditioned medium to 95oC abolishes the increase in attachment to epithelial cells. A similar decrease was observed when the conditioned medium was treated with proteinase-K to degrade the proteins. The secreted molecule(s) was found to be larger than 3 kDa and strongly suggests that the HCT-8 secreted molecule that increases EHEC virulence and colonization is a protein-based molecule. Affymetrix E. coli Genome 2.0 Arrays were used to determine the changes in EHEC virulence gene expression on exposure to intestinal epithelial cell-secreted factors (through growth in conditioned medium). Overnight cultures of EHEC were diluted in LB medium to a turbidity of 0.1 at 600 nm. The cells were allowed to grow to a turbidity of 1.0 at 600 nm at 37°C and the EHEC cells were then resuspended in either fresh or conditioned medium. The cultures were then allowed to grow for 1 h or 3 h before cell pellets were collected by centrifugation and stored at -80°C. Total RNA was isolated from the cell pellets (173) and RNA quality was assessed using gel electrophoresis. Escherichia coli Genome 2.0 arrays (Affymetrix, Santa Clara, CA, USA) containing 10,208 probe sets for all 20,366 genes present in four strains of E. coli, including EHEC, were used to profile changes in gene expression using RNA samples for each treatment.
2012-10-04 | E-GEOD-22285 | biostudies-arrayexpress
Project description:In this study, we determined the sequences of four intimin variant genes detected in attaching and effacing Escherichia coli isolates of human origin. Three of them were novel and were designated eae-eta (eta), eae-iota (iota), and eae-kappa (kappa). The fourth was identical to the recently described eae-zeta (zeta), isolated from a bovine E. coli O84:NM isolate. We compared these sequences with those of published intimin-alpha, intimin-beta, intimin-gamma1, intimin-gamma2, intimin- epsilon, and intimin-theta alleles. Sequence analysis of these 10 intimin alleles confirmed extensive genetic diversity within the intimin gene family in E. coli. The genetic diversity was more prominent in the 3' region (starting at bp 2,112), which encodes the binding domain of intimin. Phylogenetic analyses revealed four groups of closely related intimin genes: alpha and zeta; beta and kappa; gamma1 and gamma2/theta; and epsilon and eta. Calculation of homoplasy ratios of sequences of the 5' region of eae (positions 1 to 2,111) revealed evidence for intragenic recombination. Split decomposition analysis also indicates that recombination events have played a role in the evolutionary history of eae. In conclusion, we recommend an eae nomenclature system based on the Greek alphabet and provide an updated PCR scheme for amplification and typing of E. coli eae.
| S-EPMC154638 | biostudies-literature
Project description:Although gut protection to infection is ensured by innate lymphoid cells (ILCs), how ILCs are regulated remains poorly understood. Here, we show that secretion of the c-type lectin Reg3b downstream of Ripk2 signaling pathway was crucial for immune surveillance by ILCs against Citrobacter rodentium that mimics human infection with attaching-and-effacing bacteria. Unexpectedly, phosphorylation of signal transducer and activator of transcription 3 (STAT3) and secretion of both tumor necrosis factor alpha (Tnf-a) and interleukin-17A (IL-17A) were blunted in mutant mice contributing to their susceptibility to a primary infection. We further determined that influx of neutrophils was triggered by Reg3b through an intact IL-17A signaling. Loss of either Reg3b or Ripk2 weakened Tnf-a secretion by intestinal phagocytes lowering their propensity to promote IL17A secretion by ILCs early in infection. These results provide a previously unrecognized mechanism by which intestinal epithelial cells reciprocally regulate early production of IL-17A by ILCs preventing from overcolonization by opportunistic enteropathogenic bacterium.
2019-03-31 | GSE95653 | GEO
Project description:The attaching and effacing Escherichia coli (AEEC) are characterized by the presence of a type III secretion system encoded by the locus of enterocyte effacement (LEE). Enterohemorrhagic E. coli (EHEC) are often identified as isolates that are LEE+ and carry the Shiga toxin (stx)-encoding phage, which are labeled Shiga toxin-producing E. coli; whereas enteropathogenic E. coli (EPEC) are LEE+ and often carry the EPEC adherence factor plasmid-encoded bundle-forming pilus (bfp) genes. All other LEE+/bfp-/stx- isolates have been historically designated atypical EPEC. These groups have been defined based on the presence or absence of a limited number of virulence factors, many of which are encoded on mobile elements. This study describes the comparative analysis of the genomes of 114 LEE+ E. coli isolates. Based on a whole-genome phylogeny and analysis of type III secretion system effectors, the AEEC are divided into five distinct genomic lineages. The LEE+/stx+/bfp- genomes were primarily divided into two genomic lineages, the O157/O55 EHEC1 and non-O157 EHEC2. The LEE+/bfp+/stx- AEEC isolates sequenced in this study separated into the EPEC1, EPEC2, and EPEC4 genomic lineages. A multiplex PCR assay for identification of each of these AEEC genomic lineages was developed. Of the 114 AEEC genomes analyzed, 31 LEE+ isolates were not in any of the known AEEC lineages and thus represent unclassified AEEC that in most cases are more similar to other E. coli pathovars than to text modification AEEC. Our findings demonstrate evolutionary relationships among diverse AEEC pathogens and the utility of phylogenomics for lineage-specific identification of AEEC clinical isolates.
| S-EPMC3732946 | biostudies-literature