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.

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

ACCESS DATA

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

Similar Datasets

Project description:Tuberculosis is caused by Mycobacterium tuberculosis (Mtb) infection. Mtb is one of the oldest human pathogens, and evolves mechanisms implied in human evolution. The lungs are the first organ exposed to aerosol-transmitted Mtb during gaseous exchange. Therefore, the guards of the immune system in the lungs, such as macrophages (M?s) and dendritic cells (DCs), are the most important defense against Mtb infection. There have been several studies discussing the functions of M?s and DCs during Mtb infection, but the genome-wide pathways and networks are still incomplete. Furthermore, the immune response induced by M?s and DCs varies. Therefore, we analyzed the cross-talk genome-wide genetic-and-epigenetic interspecies networks (GWGEINs) between M?s vs. Mtb and DCs vs. Mtb to determine the varying mechanisms of both the host and pathogen as it relates to M?s and DCs during early Mtb infection. First, we performed database mining to construct candidate cross-talk GWGEIN between human cells and Mtb. Then we constructed dynamic models to characterize the molecular mechanisms, including intraspecies gene/microRNA (miRNA) regulation networks (GRNs), intraspecies protein-protein interaction networks (PPINs), and the interspecies PPIN of the cross-talk GWGEIN. We applied a system identification method and a system order detection scheme to dynamic models to identify the real cross-talk GWGEINs using the microarray data of M?s, DCs and Mtb. After identifying the real cross-talk GWGEINs, the principal network projection (PNP) method was employed to construct host-pathogen core networks (HPCNs) between M?s vs. Mtb and DCs vs. Mtb during infection process. Thus, we investigated the underlying cross-talk mechanisms between the host and the pathogen to determine how the pathogen counteracts host defense mechanisms in M?s and DCs during Mtb H37Rv early infection. Based on our findings, we propose Rv1675c as a potential drug target because of its important defensive role in M?s. Furthermore, the membrane essential proteins v1098c, and Rv1696 (or cytoplasm for Rv0667), in Mtb could also be potential drug targets because of their important roles in Mtb survival in both cell types. We also propose the drugs Lopinavir, TMC207, ATSM, and GTSM as potential therapeutic treatments for Mtb infection since they target the above potential drug targets.

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.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets