Module 393

Bookmark

Summary

Residual	Gene Count	Condition Count	1st Q Condition Block *	5th Q Condition Block *
0.46	26	62	NA	NA

Bicluster expression profile

Expression of genes in subset of conditions included in bicluster on left side of red dashed line and out of bicluster on right of red dashed line. Each condition is represented as a boxplot, ordered by their median expression for the bicluster genes (smallest to largest) and colored according to condition blocks.

Boxplot test

Module Enrichment profile

Gene expression profiles across conditions are sorted as on the left and broken into quintiles following the dashed grey lines. Then each quintile is tested for enrichment of each condition by using hypergeometric test. The deviation from zero indicates over-enrichment.

Boxplot test

Conditions

codY knockout codY knockout Integration of metabolism and virulence by Clostridium difficile CodY Series: GSE23192 \| Pubmed ID: 20709897 \| Type: Expression profiling by array Summary:CodY, a global regulatory protein that monitors the nutrient sufficiency of the environment by responding to the intracellular levels of GTP and the branched-chain amino acids, was previously shown to be a potent repressor of toxin gene expression in Clostridium difficile during growth in rich medium. In the intestinal tract, such derepression of toxin synthesis may lead to destruction of epithelial cells and the liberation of potential nutrients for the bacterium. CodY is likely to play an important role in regulating overall cellular physiology as well. In this study, DNA microarray analysis and affinity purification of CodY-DNA complexes were used to identify and distinguish the direct and indirect effects of CodY on global gene transcription. A codY null mutation resulted in >4-fold overexpression of 146 genes (organized in 82 apparent transcription units) and underexpression of 19 genes. In addition to the toxin genes, genes for amino acid biosynthesis, nutrient transport, fermentation pathways, membrane components and surface proteins were overexpressed in the codY mutant. Genome-wide analysis identified more than 350 CodY binding regions, many of which are likely to correspond to sites of direct CodY-mediated regulation. About 60% of the CodY-repressed transcription units were associated with binding regions. Several of these genes were confirmed to be direct targets of CodY by gel mobility shift and DNase I footprinting assays. Overall Design:The experiment was designed to compare gene expression in codY+ and codY mutant strains grown to mid-exponential phase. Three two-color arrays, representing three biological replicates. Each array compares two strains: JIR8094 (pSD21) and JIR9084::pSD21. Samples: GSM570801, GSM570802, GSM570803	In vivo vs. In vitro In vivo vs. In vitro Comparison of the expression profiles of the 630E strain after 8h, 14h and 38h of infection in mouse Series: GSE43303,GSE43305 \| Pubmed ID: 23897605 \| Type: Expression profiling by array Summary: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. Overall Design: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. Samples: GSM1060320, GSM1060321, GSM1060322, GSM1060323, GSM1060324, GSM1060325, GSM1060326, GSM1060327, GSM1060328, GSM1060329, GSM1060330, GSM1060331, GSM1060332, GSM1060333, GSM1060334, GSM1060335, GSM1060336, GSM1060337, GSM1060338, GSM1060339, GSM1060340, GSM1060341, GSM1060342, GSM1060343, GSM1060344, GSM1060345, GSM1060346, GSM1060347, GSM1060348, GSM1060349, GSM1060350, GSM1060351	Early infection Early infection Transcription profiling of Caco-2 cells and Clostridium difficile during infection Series: GSE18407 \| Pubmed ID: 20521945 \| Type: Expression profiling by array Summary: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. Overall Design: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 Samples: GSM458943, GSM458942, GSM458941, GSM458940, GSM458939, GSM458938, GSM458937, GSM458936, GSM458935, GSM458934, GSM458933, GSM458932
Rich vs poor diet Rich vs poor diet The in vivo responses elicited by Clostridium difficile in response to the gut commensal B. thetaiotaomicron and diet Series: GSE60751 \| Pubmed ID: \| Type: Expression profiling by array Summary:Analysis of Clostridium difficile (Cd) from the cecal contents of germ-free mice or Bacteroides thetaiotaomicron (Bt)-monocolonized mice on a standard, polysaccharide rich diet or polysaccharide deficient diet 5 days after infection. Results identify genes that are involved in the Cd response to diet, in vivo colonization and in interactions with Bt. Overall Design:In vitro transcriptional profiles of Clostridium difficile obtained from cecal contents of germ-free or Bt-monocolonized mice on a standard, polysaccharide rich or polysaccharide deficient diet. 4 samples/group. 2 control genomic DNA samples for Clostridium difficile and 2 reference genomic DNA samples for Bacteroides thetaiotaomicron; ; Please note that 4 control samples (genomic DNA) were used to determine whether the genomic DNA correctly bound to the probes and thus, were not included in data processing (i.e no processed/normalized data). Samples: GSM1487085, GSM1487086, GSM1487087, GSM1487088, GSM1487089, GSM1487090, GSM1487092, GSM1487091	fur knockout fur knockout Expression analysis of Clostridium difficile wild type and fur (ferric uptake regulator) mutant in high iron. Series: GSE69218 \| Pubmed ID: \| Type: Expression profiling by array Summary:Investigation of whole genome gene expression level changes in a Clostridium difficile fur (ferric uptake regulator) mutant, compared to the wild type strain 630 erm.; The fur mutant analyzed in this study is further described in Ho and Ellermeier (2015) J. Bacteriology Overall Design:A microarray study using total RNA recovered from three separate wild type cultures of Clostridium difficile 630 erm strain and three separate cultures of a fur mutant strain (ltrA::ermR) were grown in Tryptone-Yeast Extract medium containing 0.25 mM ferric chloride . Each chip measures the expression level of 3,786 of the 3,787 open reading frames of the C. difficile 630 genome with 18 probes (60 oligomers each) for each gene. Samples: GSM1695516, GSM1695517, GSM1695518, GSM1695519, GSM1695520, GSM1695521, fur.high.11, fur.high.1.1, fur.high.21, fur.high2.1, fur.high.31, fur.high3.1, fur.low.1, fur.low.2, fur.low2, fur.low.3, fur.low3	Commensal vs germ free Commensal vs germ free The in vivo responses elicited by Clostridium difficile in response to the gut commensal B. thetaiotaomicron and diet Series: GSE60751 \| Pubmed ID: \| Type: Expression profiling by array Summary:Analysis of Clostridium difficile (Cd) from the cecal contents of germ-free mice or Bacteroides thetaiotaomicron (Bt)-monocolonized mice on a standard, polysaccharide rich diet or polysaccharide deficient diet 5 days after infection. Results identify genes that are involved in the Cd response to diet, in vivo colonization and in interactions with Bt. Overall Design:In vitro transcriptional profiles of Clostridium difficile obtained from cecal contents of germ-free or Bt-monocolonized mice on a standard, polysaccharide rich or polysaccharide deficient diet. 4 samples/group. 2 control genomic DNA samples for Clostridium difficile and 2 reference genomic DNA samples for Bacteroides thetaiotaomicron; ; Please note that 4 control samples (genomic DNA) were used to determine whether the genomic DNA correctly bound to the probes and thus, were not included in data processing (i.e no processed/normalized data). Samples: GSM1487081, GSM1487082, GSM1487083, GSM1487084, GSM1487089, GSM1487090, GSM1487091, GSM1487092
Response to oxygen Response to oxygen Clostridium difficile response to oxygen Series: GSE109175 \| Pubmed ID: \| Type: Expression profiling by array Summary:C. difficile was grown in either anaerobic conditions or 2% oxygen and gene expression was compared Overall Design:C. difficile was grown in either anaerobic conditions or 2% oxygen and gene expression was compared. Two conditions were tested with three replicates each (6 samples total) Samples: GSM2934766, GSM2934767, GSM2934768	Exponential to stationary phase Exponential to stationary phase Metabolic reprogramming with the induction of toxin production of Clostridioides difficile during the stationary phase Series: GSE115054 \| Pubmed ID: \| Type: Expression profiling by array Summary:Systems biology approach of Clostridioides difficile to analyze the temporal changes in the intracellular and extracellular metabolme, transcriptome and proteome along the growth curve in casamino acids medium and the connection to toxin production. Overall Design:Clostridioides difficile 630∆erm (DSM28645) were grown in a casamino acids medium (CDMM) containing 2 g/L glucose. Samples were taken at five time points along the growth curve (exponential growth: 14.5 h of cultivation, transient phase: 17.25 h, stationary phase 1: 19.25 h, stationary phase 2: 24.25 h, stationary phase 3: 29.25 h). The cultivation was performed with four biological replicates. Reference in transcriptomic acid proteomic measurement was the exponential phase samples. Samples: GSM3164188, GSM3164189, GSM3164190, GSM3164191, GSM3164192, GSM3164193, GSM3164194, GSM3164195, GSM3164196, GSM3164197, GSM3164198, GSM3164199, GSM3164200, GSM3164201, GSM3164202, GSM3164203	Sporulation Sporulation NA Series: NA \| Pubmed ID: \| Type: NA Summary:NA Overall Design:NA Samples: S01.RD, S02.RD, S03.RD, E1.RD, E2.RD, E3.RD, F1.RD, F2.RD, F3.RD, K1.RD, K2.RD, K3.RD, G1.RD, G2.RD, G3.RD, spoIIID.1_S19.RD, spoIIID.2_S20.RD, spoIIID.3_S21.RD
Iron limiting condition Iron limiting condition Clostridium difficile response to iron limitation Series: GSE109453 \| Pubmed ID: \| Type: Expression profiling by array Summary:C. difficile was grown in BHIS broth or BHIS broth with 75uM dipridyl and gene expression was compared. Overall Design:Two conditions were tested at three timepoints with three replicates each (18 samples total). Samples: GSM2943576, GSM2943577, GSM2943578, GSM2943582, GSM2943583, GSM2943584, GSM2943588, GSM2943589, GSM2943590, WT.high.1, WT.high.2, WT.high.3, fur.high.1, fur.high.2, fur.high2, fur.high.3, fur.high3

de novo identified motifs are listed below

Motif 1	Motif 1 e-value		Motif 2	Motif 2 e-value
GAGAGGAGAAA	0.0000000000019		NA	NA

This module is predicted to be regulated by the following regulators by using inferelator

Candidate transcriptional regulators for each module were determined with a linear regression based approach (Inferelator) and by evaluating the statistical significance of the overlap (Hypergeometric) between modules and putative TF and alternative sigma factor regulons (CcpA, CodY, Fur, PrdR, SigB, SigD, SigE, SigF, SigG, SigH, SigK, Spo0A) compiled from available literature.

For filtering high confidence influences, we used hypergeometric test adjusted p-value <=0.05 and minimum four genes in the overlap between the module and the TF regulon. The same thresholds were used for evaluating the functional enrichment.

1. Betas: correspond to the average coefficients of the Bayesian regressions between module expression and TF expression profiles. The values indicate the magnitude and direction (activation or repression for positive or negative values, respectively) of each TF-module interaction. 2. Confidence scores: indicate the likelihood of the TF-module interactions.

TF	Module	Confidence Score	Beta
CD630_23900 Transcriptional regulator, beta-lactamsrepressor	393	0.27	0.1729
CD630_18100 Transcriptional regulator, beta-lactamsrepressor	393	0.14	0.1334
CD630_16920 Transcriptional regulator, ArsR family	393	0.22	0.1251

This module is predicted to be regulated by the following regulators by using hypergeometric

TF	Module	Overlap	pvalue	Adjusted pvalue
CD630_32450 prdR Transcriptional regulator, sigma-54-dependent	393	8	0.00	0.00

The module is significantly enriched with genes associated to the indicated functional terms

No functional enrichments were found with default filters.

Genes that are included in this module

* "Gene essentiality is based on TnSeq Data from: Dembek M, Barquist L, Boinett CJ, et al. High-throughput analysis of gene essentiality and sporulation in Clostridium difficile. mBio. 2015;6(2):e02383. Published 2015 Feb 24.doi:10.1128/mBio.02383-14".

Displaying 1 - 26 of 26

Title	Short Name	Product	Function	Essentiality *	in vivo Essentiality	Rich broth Essentiality
CD630_00670	rpoC	DNA-directed RNA polymerase subunit beta'	DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.	Yes
CD630_26720	appA	ABC-type transport system, oligopeptide-familysolute-binding protein
CD630_26700	appF	ABC-type transport system, ATP-binding protein
CD630_28520	dltB	D-alanyl transferase DltB, MBOAT family	Could be involved in the transport of activated D-alanine through the membrane.
CD630_05480		Putative penicillin-binding peptidase BlaR1-like,M56 family
CD630_28540	dltD	D-alanine transferase
CD630_35560		Putative membrane protein
CD630_28510	dltC	D-alanine--poly(phosphoribitol) ligase subunit 2(D-alanyl carrier protein) (DCP)	Carrier protein involved in the D-alanylation of lipoteichoic acid (LTA). The loading of thioester-linked D-alanine onto DltC is catalyzed by D-alanine--D-alanyl carrier protein ligase DltA. The DltC-carried D-alanyl group is further transferred to cell membrane phosphatidylglycerol (PG) by forming an ester bond, probably catalyzed by DltD. D-alanylation of LTA plays an important role in modulating the properties of the cell wall in Gram-positive bacteria, influencing the net charge of the cell wall.
CD630_35540	dusB	tRNA-dihydrouridine synthase	Catalyzes the synthesis of 5,6-dihydrouridine (D), a modified base found in the D-loop of most tRNAs, via the reduction of the C5-C6 double bond in target uridines.
CD630_35520	lysS	Lysyl-tRNA synthetase (Lysine--tRNA ligase)(LysRS)		Yes
CD630_18100		Transcriptional regulator, beta-lactamsrepressor
CD630_07040		Putative metal-dependent phosphohydrolase
CD630_26710	appD	ABC-type transport system, ATP-binding protein
CD630_00660	rpoB	DNA-directed RNA polymerase subunit beta	DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.	Yes
CD630_35580	birA	BirA bifunctional protein [Includes: biotinoperon repressor and biotin--[acetyl-CoA-carboxylase]synthetase	Acts both as a biotin--[acetyl-CoA-carboxylase] ligase and a repressor.
CD630_28530	dltA	D-alanine--poly(phosphoribitol) ligase subunit 1	Catalyzes the first step in the D-alanylation of lipoteichoic acid (LTA), the activation of D-alanine and its transfer onto the D-alanyl carrier protein (Dcp) DltC. In an ATP-dependent two-step reaction, forms a high energy D-alanyl-AMP intermediate, followed by transfer of the D-alanyl residue as a thiol ester to the phosphopantheinyl prosthetic group of the Dcp. D-alanylation of LTA plays an important role in modulating the properties of the cell wall in Gram-positive bacteria, influencing the net charge of the cell wall.
CD630_19630		Putative methyltransferase
CD630_35570		Putative peptidase
CD630_35530	greA	Transcription elongation factor greA (Transcriptcleavage factor GreA)	Necessary for efficient RNA polymerase transcription elongation past template-encoded arresting sites. The arresting sites in DNA have the property of trapping a certain fraction of elongating RNA polymerases that pass through, resulting in locked ternary complexes. Cleavage of the nascent transcript by cleavage factors such as GreA or GreB allows the resumption of elongation from the new 3'terminus. GreA releases sequences of 2 to 3 nucleotides.	Yes
CD630_35550	coaX	Type III pantothenate kinase (Pantothenic acidkinase) (PanK-III)	Catalyzes the phosphorylation of pantothenate (Pan), the first step in CoA biosynthesis.	Yes	Yes	Yes
CD630_02030		Putative UvrABC system protein A 1 (UvrA protein1) (Excinuclease ABC subunit A 1)	The UvrABC repair system catalyzes the recognition and processing of DNA lesions. UvrA is an ATPase and a DNA-binding protein. A damage recognition complex composed of 2 UvrA and 2 UvrB subunits scans DNA for abnormalities. When the presence of a lesion has been verified by UvrB, the UvrA molecules dissociate.
CD630_07030		Putative peptidase, U32 family
CD630_07050		Putative hydrolase, NUDIX family
CD630_36690		Putative lipoprotein
CD630_05470		Transcriptional regulator, beta-lactamsrepressor		Yes
CD630_26740	appC	ABC-type transport system, oligopeptide-familypermease protein

codY knockout codY knockout Integration of metabolism and virulence by Clostridium difficile CodY Series: GSE23192 \| Pubmed ID: 20709897 \| Type: Expression profiling by array Summary:CodY, a global regulatory protein that monitors the nutrient sufficiency of the environment by responding to the intracellular levels of GTP and the branched-chain amino acids, was previously shown to be a potent repressor of toxin gene expression in Clostridium difficile during growth in rich medium. In the intestinal tract, such derepression of toxin synthesis may lead to destruction of epithelial cells and the liberation of potential nutrients for the bacterium. CodY is likely to play an important role in regulating overall cellular physiology as well. In this study, DNA microarray analysis and affinity purification of CodY-DNA complexes were used to identify and distinguish the direct and indirect effects of CodY on global gene transcription. A codY null mutation resulted in >4-fold overexpression of 146 genes (organized in 82 apparent transcription units) and underexpression of 19 genes. In addition to the toxin genes, genes for amino acid biosynthesis, nutrient transport, fermentation pathways, membrane components and surface proteins were overexpressed in the codY mutant. Genome-wide analysis identified more than 350 CodY binding regions, many of which are likely to correspond to sites of direct CodY-mediated regulation. About 60% of the CodY-repressed transcription units were associated with binding regions. Several of these genes were confirmed to be direct targets of CodY by gel mobility shift and DNase I footprinting assays. Overall Design:The experiment was designed to compare gene expression in codY+ and codY mutant strains grown to mid-exponential phase. Three two-color arrays, representing three biological replicates. Each array compares two strains: JIR8094 (pSD21) and JIR9084::pSD21. Samples: GSM570801, GSM570802, GSM570803	In vivo vs. In vitro In vivo vs. In vitro Comparison of the expression profiles of the 630E strain after 8h, 14h and 38h of infection in mouse Series: GSE43303,GSE43305 \| Pubmed ID: 23897605 \| Type: Expression profiling by array Summary: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. Overall Design: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. Samples: GSM1060320, GSM1060321, GSM1060322, GSM1060323, GSM1060324, GSM1060325, GSM1060326, GSM1060327, GSM1060328, GSM1060329, GSM1060330, GSM1060331, GSM1060332, GSM1060333, GSM1060334, GSM1060335, GSM1060336, GSM1060337, GSM1060338, GSM1060339, GSM1060340, GSM1060341, GSM1060342, GSM1060343, GSM1060344, GSM1060345, GSM1060346, GSM1060347, GSM1060348, GSM1060349, GSM1060350, GSM1060351	Early infection Early infection Transcription profiling of Caco-2 cells and Clostridium difficile during infection Series: GSE18407 \| Pubmed ID: 20521945 \| Type: Expression profiling by array Summary: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. Overall Design: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 Samples: GSM458943, GSM458942, GSM458941, GSM458940, GSM458939, GSM458938, GSM458937, GSM458936, GSM458935, GSM458934, GSM458933, GSM458932
Rich vs poor diet Rich vs poor diet The in vivo responses elicited by Clostridium difficile in response to the gut commensal B. thetaiotaomicron and diet Series: GSE60751 \| Pubmed ID: \| Type: Expression profiling by array Summary:Analysis of Clostridium difficile (Cd) from the cecal contents of germ-free mice or Bacteroides thetaiotaomicron (Bt)-monocolonized mice on a standard, polysaccharide rich diet or polysaccharide deficient diet 5 days after infection. Results identify genes that are involved in the Cd response to diet, in vivo colonization and in interactions with Bt. Overall Design:In vitro transcriptional profiles of Clostridium difficile obtained from cecal contents of germ-free or Bt-monocolonized mice on a standard, polysaccharide rich or polysaccharide deficient diet. 4 samples/group. 2 control genomic DNA samples for Clostridium difficile and 2 reference genomic DNA samples for Bacteroides thetaiotaomicron; ; Please note that 4 control samples (genomic DNA) were used to determine whether the genomic DNA correctly bound to the probes and thus, were not included in data processing (i.e no processed/normalized data). Samples: GSM1487085, GSM1487086, GSM1487087, GSM1487088, GSM1487089, GSM1487090, GSM1487092, GSM1487091	fur knockout fur knockout Expression analysis of Clostridium difficile wild type and fur (ferric uptake regulator) mutant in high iron. Series: GSE69218 \| Pubmed ID: \| Type: Expression profiling by array Summary:Investigation of whole genome gene expression level changes in a Clostridium difficile fur (ferric uptake regulator) mutant, compared to the wild type strain 630 erm.; The fur mutant analyzed in this study is further described in Ho and Ellermeier (2015) J. Bacteriology Overall Design:A microarray study using total RNA recovered from three separate wild type cultures of Clostridium difficile 630 erm strain and three separate cultures of a fur mutant strain (ltrA::ermR) were grown in Tryptone-Yeast Extract medium containing 0.25 mM ferric chloride . Each chip measures the expression level of 3,786 of the 3,787 open reading frames of the C. difficile 630 genome with 18 probes (60 oligomers each) for each gene. Samples: GSM1695516, GSM1695517, GSM1695518, GSM1695519, GSM1695520, GSM1695521, fur.high.11, fur.high.1.1, fur.high.21, fur.high2.1, fur.high.31, fur.high3.1, fur.low.1, fur.low.2, fur.low2, fur.low.3, fur.low3	Commensal vs germ free Commensal vs germ free The in vivo responses elicited by Clostridium difficile in response to the gut commensal B. thetaiotaomicron and diet Series: GSE60751 \| Pubmed ID: \| Type: Expression profiling by array Summary:Analysis of Clostridium difficile (Cd) from the cecal contents of germ-free mice or Bacteroides thetaiotaomicron (Bt)-monocolonized mice on a standard, polysaccharide rich diet or polysaccharide deficient diet 5 days after infection. Results identify genes that are involved in the Cd response to diet, in vivo colonization and in interactions with Bt. Overall Design:In vitro transcriptional profiles of Clostridium difficile obtained from cecal contents of germ-free or Bt-monocolonized mice on a standard, polysaccharide rich or polysaccharide deficient diet. 4 samples/group. 2 control genomic DNA samples for Clostridium difficile and 2 reference genomic DNA samples for Bacteroides thetaiotaomicron; ; Please note that 4 control samples (genomic DNA) were used to determine whether the genomic DNA correctly bound to the probes and thus, were not included in data processing (i.e no processed/normalized data). Samples: GSM1487081, GSM1487082, GSM1487083, GSM1487084, GSM1487089, GSM1487090, GSM1487091, GSM1487092
Response to oxygen Response to oxygen Clostridium difficile response to oxygen Series: GSE109175 \| Pubmed ID: \| Type: Expression profiling by array Summary:C. difficile was grown in either anaerobic conditions or 2% oxygen and gene expression was compared Overall Design:C. difficile was grown in either anaerobic conditions or 2% oxygen and gene expression was compared. Two conditions were tested with three replicates each (6 samples total) Samples: GSM2934766, GSM2934767, GSM2934768	Exponential to stationary phase Exponential to stationary phase Metabolic reprogramming with the induction of toxin production of Clostridioides difficile during the stationary phase Series: GSE115054 \| Pubmed ID: \| Type: Expression profiling by array Summary:Systems biology approach of Clostridioides difficile to analyze the temporal changes in the intracellular and extracellular metabolme, transcriptome and proteome along the growth curve in casamino acids medium and the connection to toxin production. Overall Design:Clostridioides difficile 630∆erm (DSM28645) were grown in a casamino acids medium (CDMM) containing 2 g/L glucose. Samples were taken at five time points along the growth curve (exponential growth: 14.5 h of cultivation, transient phase: 17.25 h, stationary phase 1: 19.25 h, stationary phase 2: 24.25 h, stationary phase 3: 29.25 h). The cultivation was performed with four biological replicates. Reference in transcriptomic acid proteomic measurement was the exponential phase samples. Samples: GSM3164188, GSM3164189, GSM3164190, GSM3164191, GSM3164192, GSM3164193, GSM3164194, GSM3164195, GSM3164196, GSM3164197, GSM3164198, GSM3164199, GSM3164200, GSM3164201, GSM3164202, GSM3164203	Sporulation Sporulation NA Series: NA \| Pubmed ID: \| Type: NA Summary:NA Overall Design:NA Samples: S01.RD, S02.RD, S03.RD, E1.RD, E2.RD, E3.RD, F1.RD, F2.RD, F3.RD, K1.RD, K2.RD, K3.RD, G1.RD, G2.RD, G3.RD, spoIIID.1_S19.RD, spoIIID.2_S20.RD, spoIIID.3_S21.RD
Iron limiting condition Iron limiting condition Clostridium difficile response to iron limitation Series: GSE109453 \| Pubmed ID: \| Type: Expression profiling by array Summary:C. difficile was grown in BHIS broth or BHIS broth with 75uM dipridyl and gene expression was compared. Overall Design:Two conditions were tested at three timepoints with three replicates each (18 samples total). Samples: GSM2943576, GSM2943577, GSM2943578, GSM2943582, GSM2943583, GSM2943584, GSM2943588, GSM2943589, GSM2943590, WT.high.1, WT.high.2, WT.high.3, fur.high.1, fur.high.2, fur.high2, fur.high.3, fur.high3

Summary

Bicluster expression profile

Module Enrichment profile

Conditions

codY knockout

In vivo vs. In vitro

Early infection

Rich vs poor diet

fur knockout

Commensal vs germ free

Response to oxygen

Exponential to stationary phase

Sporulation

Iron limiting condition

de novo identified motifs are listed below

This module is predicted to be regulated by the following regulators by using inferelator

This module is predicted to be regulated by the following regulators by using hypergeometric

The module is significantly enriched with genes associated to the indicated functional terms

Genes that are included in this module