Comparison of the expression profiles of the Clostridium difficile 630E strain after 8h, 14h and 38h of infection in mouse and after 8h, 14h and 38h growth in vitro
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ABSTRACT:
ORGANISM(S): [Clostridium] difficile
SUBMITTER: Monot Marc
PROVIDER: E-GEOD-43305 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Adaptive strategies and pathogenesis of Clostridium difficile from in vivo transcriptomics.
Janoir Claire C Denève Cécile C Bouttier Sylvie S Barbut Frédéric F Hoys Sandra S Caleechum Laxmee L Chapetón-Montes Diana D Pereira Fátima C FC Henriques Adriano O AO Collignon Anne A Monot Marc M Dupuy Bruno B
Infection and immunity 20130729 10
Clostridium difficile is currently the major cause of nosocomial intestinal diseases associated with antibiotic therapy in adults. In order to improve our knowledge of C. difficile-host interactions, we analyzed the genome-wide temporal expression of C. difficile 630 genes during the first 38 h of mouse colonization to identify genes whose expression is modulated in vivo, suggesting that they may play a role in facilitating the colonization process. In the ceca of the C. difficile-monoassociated ...[more]
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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: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:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-02-20 | E-GEOD-43202 | biostudies-arrayexpress
Project description:Compartment-specific control of gene expression during Bacillus subtilis sporulation is governed by a cascade of four sigma factors, sigmaF and sigmaG in the forespore and sigmaE and sigmaK in the mother cell. In this work, we combined transcriptional analyses and transcriptional start site mapping to define the sigmaF, sigmaE, sigmaG and sigmaK regulons in Clostridium difficile. A total of about 225 genes were under the control of these sigma factors: 25 in the sigmaF regulon, 97 sigmaE-dependent genes, 50 sigmaG-governed genes and 56 genes specifically controlled by sigmaK. A significant fraction of genes in each regulon are of unknown function and we can propose new candidates for spore coat proteins synthesized under the control of sigmaE and sigmaK among proteins previously detected in the spore proteome (Lawley et al., 2009 (PMID 19542279)). Global analysis of developmental gene expression under the control of these sigma factors indicate deviations from the B. subtilis model regarding the communication between mother cell and forespore in C. difficile. We show that the expression of the sigmaE regulon in the mother cell is not strictly under the control of sigmaF despite the fact that the forespore product SpoIIR is required for the processing of pro-sigmaE. In addition, the sigmaK regulon is not controlled by sigmaG in C. difficile in connection with the lack of pro-sigmaK processing in this bacterium. However, a control of the forespore on sigmaK targets is maintained through a sigmaF-dependent regulation of sigmaK-controlled genes, a process that bypasses sigmaG. Here, transcriptional profiling of the Clostridium difficile 630E strain vs. a sigE mutant after 14h of growth in MS is performed. Two-condition experiment: 630E strain 14h vs. sigE mutant 14h. 4 biological replicates for each condition, including dye-swaps.
2014-02-20 | E-GEOD-43198 | biostudies-arrayexpress
Project description:Compartment-specific control of gene expression during Bacillus subtilis sporulation is governed by a cascade of four sigma factors, sigmaF and sigmaG in the forespore and sigmaE and sigmaK in the mother cell. In this work, we combined transcriptional analyses and transcriptional start site mapping to define the sigmaF, sigmaE, sigmaG and sigmaK regulons in Clostridium difficile. A total of about 225 genes were under the control of these sigma factors: 25 in the sigmaF regulon, 97 sigmaE-dependent genes, 50 sigmaG-governed genes and 56 genes specifically controlled by sigmaK. A significant fraction of genes in each regulon are of unknown function and we can propose new candidates for spore coat proteins synthesized under the control of sigmaE and sigmaK among proteins previously detected in the spore proteome (Lawley et al., 2009 (PMID 19542279)). Global analysis of developmental gene expression under the control of these sigma factors indicate deviations from the B. subtilis model regarding the communication between mother cell and forespore in C. difficile. We show that the expression of the sigmaE regulon in the mother cell is not strictly under the control of sigmaF despite the fact that the forespore product SpoIIR is required for the processing of pro-sigmaE. In addition, the sigmaK regulon is not controlled by sigmaG in C. difficile in connection with the lack of pro-sigmaK processing in this bacterium. However, a control of the forespore on sigmaK targets is maintained through a sigmaF-dependent regulation of sigmaK-controlled genes, a process that bypasses sigmaG. Here, transcriptional profiling of the Clostridium difficile 630E strain vs. a sigE mutant after 14h of growth in MS is performed. Two-condition experiment: 630E strain 14h vs. sigF mutant 14h. 4 biological replicates for each condition, including dye-swaps.
2014-02-20 | E-GEOD-43199 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-07-15 | E-GEOD-55274 | biostudies-arrayexpress
Project description:Compartment-specific control of gene expression during Bacillus subtilis sporulation is governed by a cascade of four sigma factors, sigmaF and sigmaG in the forespore and sigmaE and sigmaK in the mother cell. In this work, we combined transcriptional analyses and transcriptional start site mapping to define the sigmaF, sigmaE, sigmaG and sigmaK regulons in Clostridium difficile. A total of about 225 genes were under the control of these sigma factors: 25 in the sigmaF regulon, 97 sigmaE-dependent genes, 50 sigmaG-governed genes and 56 genes specifically controlled by sigmaK. A significant fraction of genes in each regulon are of unknown function and we can propose new candidates for spore coat proteins synthesized under the control of sigmaE and sigmaK among proteins previously detected in the spore proteome (Lawley et al., 2009 (PMID 19542279)). Global analysis of developmental gene expression under the control of these sigma factors indicate deviations from the B. subtilis model regarding the communication between mother cell and forespore in C. difficile. We show that the expression of the sigmaE regulon in the mother cell is not strictly under the control of sigmaF despite the fact that the forespore product SpoIIR is required for the processing of pro-sigmaE. In addition, the sigmaK regulon is not controlled by sigmaG in C. difficile in connection with the lack of pro-sigmaK processing in this bacterium. However, a control of the forespore on sigmaK targets is maintained through a sigmaF-dependent regulation of sigmaK-controlled genes, a process that bypasses sigmaG. Here, transcriptional profiling of the Clostridium difficile 630E strain vs. a sigG mutant after 19h of growth in MS is performed. Two-condition experiment: 630E strain 19h vs. sigG mutant 19h. 4 biological replicates for each condition, including dye-swaps.
2014-02-20 | E-GEOD-43200 | biostudies-arrayexpress
Project description:Compartment-specific control of gene expression during Bacillus subtilis sporulation is governed by a cascade of four sigma factors, sigmaF and sigmaG in the forespore and sigmaE and sigmaK in the mother cell. In this work, we combined transcriptional analyses and transcriptional start site mapping to define the sigmaF, sigmaE, sigmaG and sigmaK regulons in Clostridium difficile. A total of about 225 genes were under the control of these sigma factors: 25 in the sigmaF regulon, 97 sigmaE-dependent genes, 50 sigmaG-governed genes and 56 genes specifically controlled by sigmaK. A significant fraction of genes in each regulon are of unknown function and we can propose new candidates for spore coat proteins synthesized under the control of sigmaE and sigmaK among proteins previously detected in the spore proteome (Lawley et al., 2009 (PMID 19542279)). Global analysis of developmental gene expression under the control of these sigma factors indicate deviations from the B. subtilis model regarding the communication between mother cell and forespore in C. difficile. We show that the expression of the sigmaE regulon in the mother cell is not strictly under the control of sigmaF despite the fact that the forespore product SpoIIR is required for the processing of pro-sigmaE. In addition, the sigmaK regulon is not controlled by sigmaG in C. difficile in connection with the lack of pro-sigmaK processing in this bacterium. However, a control of the forespore on sigmaK targets is maintained through a sigmaF-dependent regulation of sigmaK-controlled genes, a process that bypasses sigmaG. Here, transcriptional profiling of the Clostridium difficile 630E strain vs. a sigE mutant after 24h of growth in MS is performed. Two-conditions experiments, 630E strain 24h vs sigK mutant 24h, 4 biological replicates for each condition
2014-02-20 | E-GEOD-43201 | biostudies-arrayexpress
Project description:Transcriptional profiling of C. difficile 630E strain vs. an Hfq antisense after 7.5h of growth inTYt. Two-conditions experiments, 630E strain vs. Hfq antisense grown in TYt, 4 biological replicates for each condition.
2014-07-15 | E-GEOD-55273 | biostudies-arrayexpress
Project description:Clostridium difficile is an emergent human pathogen and the most common cause of nosocomial diarrhea. Our recent deep-sequencing data strongly suggest the importance of RNA-based mechanisms for the control of gene expression in C. difficile. The RNA chaperon protein Hfq is a key component of post-transcriptional regulatory network in various bacterial systems. In an effort to understand the function of Hfq in C. difficile, we have constructed and characterized an Hfq-depleted strain in this bacterium. We present evidence that Hfq is necessary for the normal cell growth, for the establishment of bacillary form and might be involved in metabolic adaptations, stress response and sporulation, important during C. difficile infection cycle. In accordance to these phenotypic changes, our transcriptome analysis revealed pleiotropic effects of Hfq on gene expression in C. difficile. This microarray analysis showed altered expression of genes encoding cell wall and membrane transport components, sporulation proteins, as well as stress response, transcriptional regulator genes and genes of unknown function. Remarkably, a great number of genes belonging to the regulon dependent on sporulation-specific sigma K factor were generally up-regulated in the strain depleted for Hfq. Many important metabolic pathways were also affected by Hfq depletion. Finally, the altered accumulation of several previously identified sRNAs suggests potential involvement of Hfq in these regulatory RNA function. Altogether, these results provide evidence for the pleiotropic role of Hfq protein in C. difficile physiology expanding our knowledge of Hfq-dependent regulation in Gram-positive bacteria. Two-conditions experiments, 630E strain vs. hfQ mutant grown in TYt, 4 biological replicates for each condition.
2014-07-15 | E-GEOD-49168 | biostudies-arrayexpress