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Investigation of the Cross-talk Mechanism in Caco-2 Cells during Clostridium difficile Infection through Genetic-and-Epigenetic Interspecies Networks: Big Data Mining and Genome-Wide Identification.

ABSTRACT: Clostridium difficile is the leading cause of nosocomial antibiotic-associated diarrhea and the major etiologic agent of pseudomembranous colitis. In severe cases, C. difficile infection (CDI) can cause toxic megacolon, intestinal perforation, and death. The intestinal epithelium is the first tissue encountered in the adhesion and colonization of C. difficile, and serves as a physical defense barrier against infection. Despite the well-characterized cytotoxicity, few studies have investigated the genome-wide interplay between host cells and C. difficile. The aim of this study is to investigate the genetic-and-epigenetic molecular mechanisms between human colorectal epithelial Caco-2 cells and C. difficile during the early (0-60?min) and late stages (30-120?min) of infection. To investigate the cross-talk mechanisms during the progression of infection, we introduced a systems biology approach using big data mining, dynamic network modeling, a genome-wide data identification method, system order detection scheme, and principal network projection method (PNP). We focused on the construction of genome-wide genetic-and-epigenetic interspecies networks (GEINs) and subsequent extraction of host-pathogen core networks (HPNs) to investigate the progression of underlying host/pathogen genetic-and-epigenetic mechanisms from the early to late stages of CDI. Based on our results, we suggest that the cell-wall proteins CD2787 and CD0237, which both play an important role in cell adhesion and pathogen defense mechanisms, can be considered as potential drug targets. In addition, the crucial proteins employed by C. difficile for sporulation, including CD1214, CD2629, and CD2643, can also be considered as potential drug targets since spore-mediated re-infection is a critical issue.

SUBMITTER: Li CW

PROVIDER: S-EPMC5539260 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Investigation of the Cross-talk Mechanism in Caco-2 Cells during Clostridium difficile Infection through Genetic-and-Epigenetic Interspecies Networks: Big Data Mining and Genome-Wide Identification.

Li Cheng-Wei CW Su Ming-He MH Chen Bor-Sen BS

Frontiers in immunology 20170802

Clostridium difficile is the leading cause of nosocomial antibiotic-associated diarrhea and the major etiologic agent of pseudomembranous colitis. In severe cases, C. difficile infection (CDI) can cause toxic megacolon, intestinal perforation, and death. The intestinal epithelium is the first tissue encountered in the adhesion and colonization of C. difficile, and serves as a physical defense barrier against infection. Despite the well-characterized cytotoxicity, few studies ...[more]

PMID: 28824629

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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

Dataset Information

Investigation of the Cross-talk Mechanism in Caco-2 Cells during Clostridium difficile Infection through Genetic-and-Epigenetic Interspecies Networks: Big Data Mining and Genome-Wide Identification.

Publications

Investigation of the Cross-talk Mechanism in Caco-2 Cells during <i>Clostridium difficile</i> Infection through Genetic-and-Epigenetic Interspecies Networks: Big Data Mining and Genome-Wide Identification.

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