Bacteria-host transcriptional response during endothelial invasion by Staphylococcus aureus
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens Staphylococcus aureus
PROVIDER: GSE151135 | GEO | 2021/03/23
REPOSITORIES: GEO
Similar Datasets
Project description:Bacteria-host transcriptional response during endothelial invasion by Staphylococcus aureus
| PRJNA634851 | ENA
Project description:Outcome and resolution of an udder inflammation (mastitis) depends on the type of the invading pathogen. Gram-negative pathogens, such as Escherichia coli mostly trigger strong inflammation and full local activation of the immune defense eventually resulting in pathogen elimination. Staphylococcus aureus and other Gram-positive pathogens elicit only weak immune reactions possibly allowing for pathogen persistence. Little is known about the very early molecular determinants of this pathogen-species specific immune response of the udder. We therefore infected healthy mid-lactating heifers with a high dose of defined E. coli1303 or S. aureus1027 pathogens, sampled udder tissues at 1, 2, and 3 h post infection and globally profiled the transcriptome of samples from the gland cistern. We expectedly found that the E. coli infection elicited a fast and strong immune response. Bioinformatics analyses suggested that pathogen recognizing receptors triggered the activation of the IkB/NF-kB signaling cascade inducing the expression of a wealth of inflammation related genes, but also many immune dampeners. S. aureus infection failed to elicit inflammation and activate IkB/NF-kB signaling. Instead, it triggered immune suppressive mechanisms which were, however not outweighed by strong induction of inflammatory genes. Moreover, it activated the wnt/b-catenin signaling cascade resulting in active suppression of NF-kB signaling and rearrangement of the actin-cytoskeleton through modulating expression of the Rho GTPases. These alterations facilitate invasion of pathogens into host cells. We validated experimentally that pathogenic S. aureus, but not E. coli may invade mammary epithelial cells (MEC). Microscopy revealed an altered structure of the actin-cytoskeleton of primary MEC having internalized live GFP-tagged S. aureus pathogens. Our study reveals for the first time the earliest host responses in the udder differentiating E. coli from S. aureus mastitis. The latter is characterized by eliciting immune suppression rather than inflammation and invasion of S. aureus into the epithelial cells of the host.
2017-08-30 | GSE94056 | GEO
Project description:The pathogen Staphylococcus aureus can invade and survive within human cells. There, the intracellular bacterium induces host cell death, which may facilitate spread of infection and tissue destruction. We here conducted a shRNA screen and infected the library of knock-down cells with S. aureus. We identified calcium signaling pathways to play a role in S. aureus invasion and cytotoxicity. For latter, the intracellular bacteria induce a cytoplasmic and mitochondrial Ca2+-overload, which results in host cell death.
2021-10-31 | GSE156073 | GEO
Project description:Staphylococcus aureus pneumonia causes significant morbidity and mortality. Alpha-hemolysin (Hla), a pore-forming cytotoxin of S. aureus, has been identified through animal models of pneumonia as a critical virulence factor that induces lung injury. In spite of considerable molecular knowledge of how this cytotoxin injures the host, the precise host response to Hla in the context of infection remains poorly understood. We employed whole-genome expression profiling of infected lung to define the host response to wild-type S. aureus compared with an Hla-deficient isogenic mutant in experimental pneumonia. These data provide a complete expression profile at four and at twenty-four hours post-infection, revealing a unique response to the toxin-expressing strain. Gene ontogeny analysis revealed significant differences in the extracellular matrix and cardiomyopathy pathways, both of which govern cellular interactions in the tissue microenvironment. Evaluation of individual transcript responses to Hla-secreting bacteria was notable for upregulation of host cytokine and chemokine genes, including the p19 subunit of interleukin-23. Consistent with this observation, the cellular immune response to infection was characterized by a prominent TH17 response to wild-type staphylococci. These findings define specific host mRNA responses to Hla-producing S. aureus, coupling the pulmonary TH17 response to the presence of this cytotoxin. Expression profiling to define the host response to a single virulence factor proved to be a valuable tool in identifying pathways for further investigation in S. aureus pneumonia. This approach may be broadly applicable to the study of bacterial toxins, defining host pathways that can be targeted to mitigate toxin-induced disease. Animals were treated with PBS, S. aureus wild-type, or S. aureus Hla-deficient isogenic mutant.
2012-05-20 | E-GEOD-38053 | biostudies-arrayexpress
Project description:Staphylococcus aureus pneumonia causes significant morbidity and mortality. Alpha-hemolysin (Hla), a pore-forming cytotoxin of S. aureus, has been identified through animal models of pneumonia as a critical virulence factor that induces lung injury. In spite of considerable molecular knowledge of how this cytotoxin injures the host, the precise host response to Hla in the context of infection remains poorly understood. We employed whole-genome expression profiling of infected lung to define the host response to wild-type S. aureus compared with an Hla-deficient isogenic mutant in experimental pneumonia. These data provide a complete expression profile at four and at twenty-four hours post-infection, revealing a unique response to the toxin-expressing strain. Gene ontogeny analysis revealed significant differences in the extracellular matrix and cardiomyopathy pathways, both of which govern cellular interactions in the tissue microenvironment. Evaluation of individual transcript responses to Hla-secreting bacteria was notable for upregulation of host cytokine and chemokine genes, including the p19 subunit of interleukin-23. Consistent with this observation, the cellular immune response to infection was characterized by a prominent TH17 response to wild-type staphylococci. These findings define specific host mRNA responses to Hla-producing S. aureus, coupling the pulmonary TH17 response to the presence of this cytotoxin. Expression profiling to define the host response to a single virulence factor proved to be a valuable tool in identifying pathways for further investigation in S. aureus pneumonia. This approach may be broadly applicable to the study of bacterial toxins, defining host pathways that can be targeted to mitigate toxin-induced disease.
2012-05-21 | GSE38053 | GEO
Project description:Analysis of strain-specific HUVEC gene expression as a response to infection by selected sepsis isolates of Staphylococcus aureus. Previous study showed great heterogeneity of endothelium pro-inflammatory response, cell death induction and translocation of bacteria through the endothelium barrier. The focus of this study was to investigate different endothelial gene expression patterns which might correspond to activation of different pathways determining various behaviour of the endothelium to the infection. Results give important information on strain-specific endothelium gene response to Staphylococcus aureus infection and give hints about important key players involved in strain-specific endothelium responses.
2019-12-01 | GSE82036 | GEO
Project description:The transcription level of a rex-deficient S. aureus mutant in comparison to its parental strain S. aureus SH1000 was analyzed using DNA microarrays.
2009-12-31 | GSE17128 | GEO
Project description:Investigation of the bovine mammary gland response to Escherichia coli and Staphylococcus aureus infection. The aims of the study were to examine the dynamics of the mammary gland response to pathogen invasion and identify general and pathogen-specific transcriptional profiles. Individual udder quarters of 12 cows were sequentially inoculated with either E. coli or S. aureus over 24 or 72 hours before culling, whilst one quarter was used as an uninfected control.
2011-05-01 | E-TABM-704 | biostudies-arrayexpress
Project description:This project is intended to study the metabolic adaptation of Methicillin-Resistant Staphylococcus aureus (MRSA) to host immunity. Because of the nature of the samples RTI RCMRC worked with Dr. Anthony R. Richardson so that the samples would be extracted at the University of North Carolina at Chapel Hill under the condition that were optimized by RTI RCMRC for broad spectrum metabolomics analysis.
2017-09-10 | ST000453 | MetabolomicsWorkbench
Project description:Staphylococcus aureus causes disease in humans and a wide array of animals. Of note, S. aureus mastitis of ruminants, including cows, sheep and goats, results in major economic losses worldwide. Extensive variation in genome content exists among S. aureus pathogenic clones. However, the genomic variation among S. aureus strains infecting different animal species has not been well examined. To investigate variation in the genome content of human and ruminant S. aureus we carried out whole genome PCR scanning (WGPS), comparative genomic hybridizations (CGH), and directed DNA sequence analysis of strains of human, bovine, ovine, and caprine origin. Extensive variation in genome content was discovered including host- and ruminant-specific genetic loci. Ovine and caprine strains were genetically allied whereas bovine strains were heterogenous in gene content. As expected, mobile genetic elements such as pathogenicity islands and bacteriophages contributed to the variation in genome content between strains. However, remarkably, most host-specific differences were restricted to regions of the conserved core genome, which contained allelic variation in genes encoding proteins of known and unknown function. Many of these proteins are predicted to be exported and could play a role in host-pathogen interactions. These data suggest that diversification of the core genome may be more important than acquisition of novel genes for S. aureus host-adaptation. The host-specific determinants identified by the whole-genome approaches adopted in the current study represent excellent targets for studies of the evolution and molecular basis of S. aureus host specificity. Keywords: Strain vs strain
2008-11-19 | GSE10187 | GEO