Journal: Microorganisms

Article Title: Exploring the Toxin-Mediated Mechanisms in Clostridioides difficile Infection

doi: 10.3390/microorganisms12051004

Figure Lengend Snippet: ( A ) Pathogenicity Locus (PaLoc). The genes tcdA and tcdB (pink arrows) encode the toxins TcdA and TcdB, respectively. The regulatory genes tcdR (positive) and tcdC (negative) modulate the transcription of tcdA and tcdB and are presented with green arrows. Genes tcdE and tcdL (grey arrows) encode a holin and an endolysin, respectively, which are involved in toxin secretion. The direction of the arrows represents the direction of transcription of the genes. ( B ) TcdA and TcdB are divided into four domains: the glycosyltransferase domain (GTD; red), the autoprotease domain (APD; blue), the delivery and receptor-binding domain (DRBD; yellow), and the combined repetitive oligopeptides (CROPs; green).

Article Snippet: The second vaccine, developed by Pfizer, was based on full-length recombinant molecules of TcdA and TcdB.

Techniques: Binding Assay

Journal: Microorganisms

Article Title: Exploring the Toxin-Mediated Mechanisms in Clostridioides difficile Infection

doi: 10.3390/microorganisms12051004

Figure Lengend Snippet: Mechanism of action of TcdA and TcdB. Toxins bind surface receptors on the colonic epithelium and are endocytosed in acidic endosomes. Low pH triggers a conformational change in the toxins resulting in pore formation and translocation of GTD and APD in the cytosol. The activation of APD results in the cleavage and release of the GTD. The GTD blocks the function of Rho and Ras GTPases by transferring the UDP-glycose to GTPases, resulting in the induction of cytoskeletal damage.

Article Snippet: The second vaccine, developed by Pfizer, was based on full-length recombinant molecules of TcdA and TcdB.

Techniques: Translocation Assay, Activation Assay, Transferring

Journal: Microorganisms

Article Title: Exploring the Toxin-Mediated Mechanisms in Clostridioides difficile Infection

doi: 10.3390/microorganisms12051004

Figure Lengend Snippet: Representation of CDI-mediated inflammatory host response. Once TcdA and TcdB destroy the intestinal epithelium, they cause damage to deeper layers of tissue such as the destruction of the myofibroblasts. The presence of toxins triggers the release of dendritic cells, neutrophils, monocytes, and macrophages from the blood vessels. IL-1β and IL-8 produced by the intestinal epithelial cells enhance inflammation and attract neutrophils to the lumen of the colon. Within, neutrophils form pseudomembranes. At the same time, toxins induce the degranulation of mast cells and the release of substance P (SP) and Calcitonin gene-related peptide (CGRP) from neurons of the enteric nervous system.

Article Snippet: The second vaccine, developed by Pfizer, was based on full-length recombinant molecules of TcdA and TcdB.

Techniques: Produced

Journal: Microorganisms

Article Title: Exploring the Toxin-Mediated Mechanisms in Clostridioides difficile Infection

doi: 10.3390/microorganisms12051004

Figure Lengend Snippet: During CDI, C. difficile toxins TcdA and TcdB can breach the intestinal barrier and enter the bloodstream, resulting in systemic toxemia. Elevated levels of these toxins in the bloodstream can cause damage outside the colon, leading to dysfunction in multiple organs such as the heart, thymus, kidneys, and brain.

Article Snippet: The second vaccine, developed by Pfizer, was based on full-length recombinant molecules of TcdA and TcdB.

Techniques: