cytochrome-c-t and Clostridium-Infections

Clostridioides difficile infection (CDI) is the leading cause of antibiotic-associated intestinal disease, resulting in severe diarrhea and fatal pseudomembranous colitis. TcdB, one of the essential virulence factors secreted by this bacterium, induces host cell apoptosis through a poorly understood mechanism. Here, we performed an RNA interference (RNAi) screen customized to Caco-2 cells, a cell line model of the intestinal epithelium, to discover host factors involved in TcdB-induced apoptosis. We identified plakoglobin, also known as junction plakoglobin (JUP) or γ-catenin, a member of the catenin family, as a novel host factor and a previously known cell death-related chromatin factor, high-mobility group box 1 (HMGB1). Disruption of those host factors by RNAi and CRISPR resulted in resistance of cells to TcdB-mediated and mitochondrion-dependent apoptosis. JUP was redistributed from adherens junctions to the mitochondria and colocalized with the antiapoptotic factor Bcl-X

Topics: Animals; Anti-Bacterial Agents; Apoptosis; Bacterial Proteins; Bacterial Toxins; Caco-2 Cells; Chromatin; Clostridioides; Clostridioides difficile; Clostridium Infections; Cytochromes c; Diarrhea; Enterotoxins; Epithelial Cells; gamma Catenin; Glycyrrhizic Acid; HMGB1 Protein; Humans; Mice; RNA, Small Interfering; Virulence Factors