About the Talk
Presenter
Saliha Ece Acuner Zorluuysal
We are excited to host Saliha Ece Acuner Zorluuysal from Istanbul Medeniyet University!
Abstract
Clostridioides difficile (C. difficile) can cause severe diarrhoea and the development of pseudomembranous colitis when it over-colonises the host’s intestinal system, usually following antibiotic use. The primary exotoxins responsible for these symptoms are Toxin A (TcdA) and Toxin B (TcdB), of which TcdB is the more pathogenic. TcdB has glucosyltransferase activity and triggers mono-glucosylation by targeting host cell enzymes (mostly Rho and Ras family GTPases) with differing selectivity. Here we aim to explain the molecular mechanism by which TcdB interacts selectively with human Rho GTPases. To that end we focused on providing structural, dynamic and transcriptomic insight into how TcdB affects the host’s intestinal epithelial cells. Building on the available experimental TcdB structures, we modelled the unknown TcdB–host protein complex structures and developed a deeper understanding of Toxin B’s effects on host Rho GTPases such as Cdc42 and Rac1. TcdB is known to interact selectively with the GDP-bound inactive states of Rho GTPases rather than their active GTP-bound states. We elucidated the mechanism of selective binding and glucosyltransferase activity on the GDP-bound states of Cdc42 and Rac1 at the molecular level.
Date: March 29th, 2024 – 1:00 PM (GMT)
Venue: Zoom