TcdB of Clostridioides difficile Mediates RAS-Dependent Necrosis in Epithelial Cells.

ABSTRACT: A Clostridioides difficile infection (CDI) is the most common nosocomial infection worldwide. The main virulence factors of pathogenic C. difficile are TcdA and TcdB, which inhibit small Rho-GTPases. The inhibition of small Rho-GTPases leads to the so-called cytopathic effect, a reorganization of the actin cytoskeleton, an impairment of the colon epithelium barrier function and inflammation. Additionally, TcdB induces a necrotic cell death termed pyknosis in vitro independently from its glucosyltransferases, which are characterized by chromatin condensation and ROS production. To understand the underlying mechanism of this pyknotic effect, we conducted a large-scale phosphoproteomic study. We included the analysis of alterations in the phosphoproteome after treatment with Tcd

SUBMITTER: Stieglitz F 

PROVIDER: S-EPMC9024770 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature