Prof. Dr. Silja Weßler (Head of the Research group “Microbial Infection and Infection” Department of Biosciences and Medical Biology, Paris-Lodron University Salzburg, Austria) will give a presentation entitled
“How bacterial proteases promote pathogenesis”.
When?: Monday, 18 July 2022, 16:00 CEST (Berlin)
Where?: via YouTube: Helmholtz HIPS - YouTube
Host: Prof. Dr. Anna Hirsch
Guests are welcome online!
Helicobacter pylori (H. pylori) is one of the most successful human pathogens colonizing the stomach of approximately 40% of the world's population throughout their lifetime. These persistent infections can lead to severe clinically relevant diseases such as ulcers, chronic gastritis, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. H. pylori expresses a broad spectrum of well-characterized virulence factors that regulate a complex network of signaling implicated in the induction and progression of H. pylori-associated disorders. Our research group identified high temperature requirement A (HtrA) as an active serine protease secreted by H. pylori, which directly cleaves the human cell adhesion protein and tumor suppressor E-cadherin presented on the surface of gastric epithelial cells. Computational designed HtrA inhibitors specifically blocked protease activity and E-cadherin shedding. HtrA-mediated E-cadherin cleavage and subsequent disruption of intercellular adhesions are now considered to be important steps in pathogenesis
that allow injection of the bacterial oncoprotein CagA at the basal membrane of polarized epithelial cells. E- cadherin was the first identified HtrA substrate. Components of the tight junction complexes (occludin, claudin-8) and desmoglein-2 were additionally discovered suggesting that HtrA targets all types of intercellular adhesion complexes to disrupt the epithelial barrier function and polarity. We are currently investigating a series of druggable H. pylori proteases that exhibit extracellular localizations since they represent innovative targets in intervention therapies.
Silja Weßler studied biology at the University of Bielefeld and the Free University of Berlin in Germany. She received her PhD with a thesis on "Mechanisms of Helicobacter pylori-induced signal transduction in epithelial cells" at the Max Plack Institute for Infection Biology in Berlin. This was followed by postdoctoral fellowships at the Max Planck Institute for Infection Biology and Schering AG. After working as a university assistant at the University of Magdeburg, she was a guest scientist at Cancer Research UK in Oxford, followed by a position as an independent junior research group leader at the Paul Ehrlich Institute in Langen. In 2008 she habilitated in "Cell Biology" at the Goethe University Frankfurt. Since March 2010 she is Professor of Microbiology in the Department of Biosciences and Medical Biology at the University of Salzburg, Austria and leads the research group “Microbial Infection and Cancer”.