Comparison of the expression profiles of the 630E strain after 8h, 14h and 38h in TY
Ontology highlight
ABSTRACT:
ORGANISM(S): Clostridioides difficile 630 Clostridioides difficile
PROVIDER: GSE43304 | GEO | 2013/11/04
SECONDARY ACCESSION(S): PRJNA185378
REPOSITORIES: GEO
Similar Datasets
Project description:The virulence factors of Clostridium difficile have been studied for many years, but the main in vivo pathogenesis processes of this bacterium has to be investigated. Especially, data on the early mechanisms of C. difficile adaptation to the host is not yet available. The objective of our study was to improve the understanding of the pathogenesis of C. difficile by the analysis of the genome-wide temporal expression of C. difficile genes during the first hours of infection. Three groups of 4 axenic mice each were challenged by vegetative cells of the 630 C. difficile strain, and sacrified at 8, 14, and 38 hours post-infection. Pure prokaryotic RNA was obtained from caecal bacteria. Comparative hybridizations on strain 630 microarrays were done using cDNA issued from an 8-hours in vitro culture as control, with a dye-swap protocol for each sample. Normalisation and statistical analysis of all data were done with different functions of the limma package. The pathogenesis of C. difficile could be seen as a result of the successful metabolic adaptation of the bacteria to its host, contributing to its persistence and multiplication, and the coordinate expression of virulence factors. Analysis of our data enlightened some of these aspects. The results support strongly a two-step infection model, since there is, during the course of infection, a significant increase in the toxins expression contrasting with a decreased expression of most of the putative colonization factors. Several paralogs of the HMW S-layer protein are also down-regulated, some of them could be strong candidates as colonisation factors. Bacterial adaptation to the microenvironment of the host is assessed by the regulation of numerous metabolic pathways, i.e., the upregulation of the ethanolamine catabolic operon or the modulation of several PTS systems. Inactivation of some putative virulence factors identified by this methodology will complete this analysis.
2013-11-04 | GSE43303 | GEO
Project description:The virulence factors of Clostridium difficile have been studied for many years, but the main in vivo pathogenesis processes of this bacterium has to be investigated. Especially, data on the early mechanisms of C. difficile adaptation to the host is not yet available. The objective of our study was to improve the understanding of the pathogenesis of C. difficile by the analysis of the genome-wide temporal expression of C. difficile genes during the first hours of infection. Three groups of 4 axenic mice each were challenged by vegetative cells of the 630 C. difficile strain, and sacrified at 8, 14, and 38 hours post-infection. Pure prokaryotic RNA was obtained from caecal bacteria. Comparative hybridizations on strain 630 microarrays were done using cDNA issued from an 8-hours in vitro culture as control, with a dye-swap protocol for each sample. Normalisation and statistical analysis of all data were done with different functions of the limma package. The pathogenesis of C. difficile could be seen as a result of the successful metabolic adaptation of the bacteria to its host, contributing to its persistence and multiplication, and the coordinate expression of virulence factors. Analysis of our data enlightened some of these aspects. The results support strongly a two-step infection model, since there is, during the course of infection, a significant increase in the toxins expression contrasting with a decreased expression of most of the putative colonization factors. Several paralogs of the HMW S-layer protein are also down-regulated, some of them could be strong candidates as colonisation factors. Bacterial adaptation to the microenvironment of the host is assessed by the regulation of numerous metabolic pathways, i.e., the upregulation of the ethanolamine catabolic operon or the modulation of several PTS systems. Inactivation of some putative virulence factors identified by this methodology will complete this analysis. Transcriptional profiling of the C. difficile 630E strain after 8h, 14h or 38h of infection in mouse. Three-condition experiments: 630E strain 8h, 14h or 38h of infection in mouse vs. 630E strain 8h in culture. 4 biological replicates for each condition in dye swap.
2013-11-04 | E-GEOD-43303 | biostudies-arrayexpress
Project description:The virulence factors of Clostridium difficile have been studied for many years, but the main in vivo pathogenesis processes of this bacterium has to be investigated. Especially, data on the early mechanisms of C. difficile adaptation to the host is not yet available. The objective of our study was to improve the understanding of the pathogenesis of C. difficile by the analysis of the genome-wide temporal expression of C. difficile genes during the first hours of infection. Three groups of 4 axenic mice each were challenged by vegetative cells of the 630 C. difficile strain, and sacrified at 8, 14, and 38 hours post-infection. Pure prokaryotic RNA was obtained from caecal bacteria. Comparative hybridizations on strain 630 microarrays were done using cDNA issued from an 8-hours in vitro culture as control, with a dye-swap protocol for each sample. Normalisation and statistical analysis of all data were done with different functions of the limma package. The pathogenesis of C. difficile could be seen as a result of the successful metabolic adaptation of the bacteria to its host, contributing to its persistence and multiplication, and the coordinate expression of virulence factors. Analysis of our data enlightened some of these aspects. The results support strongly a two-step infection model, since there is, during the course of infection, a significant increase in the toxins expression contrasting with a decreased expression of most of the putative colonization factors. Several paralogs of the HMW S-layer protein are also down-regulated, some of them could be strong candidates as colonisation factors. Bacterial adaptation to the microenvironment of the host is assessed by the regulation of numerous metabolic pathways, i.e., the upregulation of the ethanolamine catabolic operon or the modulation of several PTS systems. Inactivation of some putative virulence factors identified by this methodology will complete this analysis. Transcriptional profiling of the C. difficile 630E strain after 8h, 14h or 38h in TY. Two-condition experiments: 630E strain 14h or 38h in TY vs. 630E strain 8h in TY. 2 biological replicates for each condition in dye swap.
2013-11-04 | E-GEOD-43304 | biostudies-arrayexpress
Project description:Clostridium difficile is a gram-positive, spore-forming enteric anaerobe which can infect humans and a wide variety of animal species. Recently, the incidence and severity of human C. difficile infection has markedly increased. In this study, we evaluated the genomic content of 73 C. difficile strains isolated from humans, horses, cattle, and pigs by comparative genomic hybridization with microarrays containing coding sequences from C. difficile strains 630 and QCD-32g58. The sequenced genome of C. difficile strain 630 was used as a reference to define a candidate core genome of C. difficile and to explore correlations between host origins and genetic diversity. Approximately 16% of the genes in strain 630 were highly conserved among all strains, representing the core complement of functional genes defining C. difficile. Absent or divergent genes in the tested strains were distributed across the entire C. difficile 630 genome and across all the predicted functional categories. Interestingly, certain genes were conserved among strains from a specific host species, but divergent in isolates with other host origins. This information provides insight into the genomic changes which might contribute to host adaptation. Due to a high degree of divergence among C. difficile strains, a core gene list from this study offers the first step toward the construction of diagnostic arrays for C. difficile.
2008-02-01 | GSE9693 | GEO
Project description:Clostridium difficile is a gram-positive, spore-forming enteric anaerobe which can infect humans and a wide variety of animal species. Recently, the incidence and severity of human C. difficile infection has markedly increased. In this study, we evaluated the genomic content of 73 C. difficile strains isolated from humans, horses, cattle, and pigs by comparative genomic hybridization with microarrays containing coding sequences from C. difficile strains 630 and QCD-32g58. The sequenced genome of C. difficile strain 630 was used as a reference to define a candidate core genome of C. difficile and to explore correlations between host origins and genetic diversity. Approximately 16% of the genes in strain 630 were highly conserved among all strains, representing the core complement of functional genes defining C. difficile. Absent or divergent genes in the tested strains were distributed across the entire C. difficile 630 genome and across all the predicted functional categories. Interestingly, certain genes were conserved among strains from a specific host species, but divergent in isolates with other host origins. This information provides insight into the genomic changes which might contribute to host adaptation. Due to a high degree of divergence among C. difficile strains, a core gene list from this study offers the first step toward the construction of diagnostic arrays for C. difficile.investigated by determining changes in transcript profiles when aerobic steady-state cultures were depleted of air.
2010-12-01 | GSE19343 | GEO
Project description:Clostridium difficile is an anaerobic spore-forming rod-shaped gram-positive bacterium that can infect both humans and animals. Most studies on the pathogenesis of C. difficile have focused on its toxins and their effect on the host cells. Recently, we utilized microarrays to identify conserved and divergent genes associated with virulence in C. difficile isolates from humans and animals. Our data provided the first clue toward a complex mechanism underlying host adaptation and pathogenesis. Microarray technology offers an efficient high-throughput tool to study the transcriptional profiles of pathogens and infected host cells. Transcriptomes of C. difficile after exposure to environmental and antibiotic stresses and those of human epithelial colorectal Caco-2 cells upon TcdA treatment have been analyzed. To our knowledge, there are still no reports on the transcriptomic study of host-pathogen interactions for C. difficile infection (CDI). In vitro analyses of interplay between host and pathogen are essential to unravel the mechanisms of infection and to investigate the host response to infection. We therefore employed microarrays to study both bacterial and human cellular transcriptome kinetics during CDI to Caco-2 cells. Here we present a large-scale analysis of transcriptional profiles to reveal molecular determinants playing a role in C. difficile pathogenesis and the host response. We found that there were 254 and 224 differentially-expressed genes after CDI in C. difficile and Caco-2 cells, respectively. These genes are clustered according to their functional categories and their potential roles in pathogenesis and host response are discussed. Our results will not only increase our understanding on the host-pathogen interaction, but may also provide targets for drug development. Clostridium difficile: Control vs Infection (time course) mRNA with genomic DNA of tested and reference strains Caco-2 cells: Control vs Infected with Clostridium difficile Time-course experiments of Caco-2 cells infected with C. difficile for 30, 60 and 120 min
2010-08-07 | E-GEOD-18407 | biostudies-arrayexpress
Project description:The pathogen Clostridioides difficile causes toxin-mediated diarrhea and is the leading cause of hospital-acquired infection in the United States. Due to growing antibiotic resistance and recurrent infection, targeting C. difficile metabolism presents a new approach to combat this infection. Genome-scale metabolic network reconstructions (GENREs) have been used to identify therapeutic targets and uncover properties that determine cellular behaviors. Thus, we constructed C. difficile GENREs for a hypervirulent isolate (strain [str.] R20291) and a historic strain (str. 630), validating both with in vitro and in vivo data sets. Growth simulations revealed significant correlations with measured carbon source usage (positive predictive value [PPV] ≥ 92.7%), and single-gene deletion analysis showed >89.0% accuracy. Next, we utilized each GENRE to identify metabolic drivers of both sporulation and biofilm formation. Through contextualization of each model using transcriptomes generated from in vitro and infection conditions, we discovered reliance on the pentose phosphate pathway as well as increased usage of cytidine and N-acetylneuraminate when virulence expression is reduced, which was subsequently supported experimentally. Our results highlight the ability of GENREs to identify novel metabolite signals in higher-order phenotypes like bacterial pathogenesis.
2023-11-27 | MODEL2205060002 | BioModels
Project description:Clostridium difficile is an anaerobic spore-forming rod-shaped gram-positive bacterium that can infect both humans and animals. Most studies on the pathogenesis of C. difficile have focused on its toxins and their effect on the host cells. Recently, we utilized microarrays to identify conserved and divergent genes associated with virulence in C. difficile isolates from humans and animals. Our data provided the first clue toward a complex mechanism underlying host adaptation and pathogenesis. Microarray technology offers an efficient high-throughput tool to study the transcriptional profiles of pathogens and infected host cells. Transcriptomes of C. difficile after exposure to environmental and antibiotic stresses and those of human epithelial colorectal Caco-2 cells upon TcdA treatment have been analyzed. To our knowledge, there are still no reports on the transcriptomic study of host-pathogen interactions for C. difficile infection (CDI). In vitro analyses of interplay between host and pathogen are essential to unravel the mechanisms of infection and to investigate the host response to infection. We therefore employed microarrays to study both bacterial and human cellular transcriptome kinetics during CDI to Caco-2 cells. Here we present a large-scale analysis of transcriptional profiles to reveal molecular determinants playing a role in C. difficile pathogenesis and the host response. We found that there were 254 and 224 differentially-expressed genes after CDI in C. difficile and Caco-2 cells, respectively. These genes are clustered according to their functional categories and their potential roles in pathogenesis and host response are discussed. Our results will not only increase our understanding on the host-pathogen interaction, but may also provide targets for drug development.
2010-08-07 | GSE18407 | GEO
Project description:Clostridium difficile is a gram-positive, spore-forming enteric anaerobe which can infect humans and a wide variety of animal species. Recently, the incidence and severity of human C. difficile infection has markedly increased. In this study, we evaluated the genomic content of 73 C. difficile strains isolated from humans, horses, cattle, and pigs by comparative genomic hybridization with microarrays containing coding sequences from C. difficile strains 630 and QCD-32g58. The sequenced genome of C. difficile strain 630 was used as a reference to define a candidate core genome of C. difficile and to explore correlations between host origins and genetic diversity. Approximately 16% of the genes in strain 630 were highly conserved among all strains, representing the core complement of functional genes defining C. difficile. Absent or divergent genes in the tested strains were distributed across the entire C. difficile 630 genome and across all the predicted functional categories. Interestingly, certain genes were conserved among strains from a specific host species, but divergent in isolates with other host origins. This information provides insight into the genomic changes which might contribute to host adaptation. Due to a high degree of divergence among C. difficile strains, a core gene list from this study offers the first step toward the construction of diagnostic arrays for C. difficile.investigated by determining changes in transcript profiles when aerobic steady-state cultures were depleted of air. Dye-swap experiments with genomic DNA of tested and reference strains 8383cy3.gpr- Cy3 – test, Cy5 – reference 8384cy3.gpr- Cy3 – test, Cy5 – reference 8384cy5.gpr- Cy3 – reference, Cy5 – test 8385cy3.gpr- Cy3 – test, Cy5 – reference 8385cy5.gpr- Cy3 – reference, Cy5 – test 8386cy3.gpr- Cy3 – test, Cy5 – reference 8525cy3.gpr- Cy3 – test, Cy5 – reference 8525cy5.gpr- Cy3 – reference, Cy5 – test 8527cy5.gpr- Cy3 – reference, Cy5 – test 8529cy5.gpr- Cy3 – reference, Cy5 – test 8531cy3.gpr- Cy3 – test, Cy5 – reference 8531cy5.gpr- Cy3 – reference, Cy5 – test 8533cy3.gpr- Cy3 – test, Cy5 – reference 8533cy5.gpr- Cy3 – reference, Cy5 – test 8596cy3.gpr- Cy3 – test, Cy5 – reference 8596cy5.gpr- Cy3 – reference, Cy5 – test 8694cy3.gpr- Cy3 – test, Cy5 – reference 8694cy5.gpr- Cy3 – reference, Cy5 – test 2 GPR files per Sample record except for 4 Sample records (GSM480414, GSM480417, GSM480419, and GSM480420) which have 1 GPR file each 4 GPR file for those Sample records are lost
2010-12-01 | E-GEOD-19343 | biostudies-arrayexpress
Project description:We illustrate how metabolically distinct species of Clostridia can protect against or worsen Clostridioides difficile infection, modulating the pathogen's colonization, growth, and virulence to impact host survival. Gnotobiotic mice colonized with the amino acid fermenter Paraclostridium bifermentans survived infection while mice colonized with the butyrate-producer, Clostridium sardiniense, more rapidly succumbed. Systematic in vivo analyses revealed how each commensal altered the gut nutrient environment, modulating the pathogen's metabolism, regulatory networks, and toxin production. Oral administration of P. bifermentans rescued conventional mice from lethal C. difficile infection via mechanisms identified in specifically colonized mice. Our findings lay the foundation for mechanistically informed therapies to counter C. difficile disease using systems biologic approaches to define host-commensal-pathogen interactions in vivo.
2021-10-04 | GSE182613 | GEO