18 October 2016 - PRESS RELEASE
How stomach germ Helicobacter pylori can cause damage
The bacterium Helicobacter pylori is an important gut pathogen and the main cause of gastric ulcers and gastric cancer. As yet it was not clear, which mechanisms play a role in these secondary complications. Scientists of the LMU and TU in Munich as well as the Essen University Hospital have discovered the important molecules and processes and thereby a completely new approach to preventing or treating infections with this bacterium. DZIF scientists have been involved in these studies, publicated in the current edition of Nature Microbiology.
In order to ensure permanent survival in the human stomach, Helicobacter pylori must attach to the epithelial cells in the gastric mucosa. This chronic infection of the epithelial cells of the gastric mucosa is presumed to be the main risk factor for gastric cancer. 700,000 people worldwide die of malignant gastric cancer every year. DZIF scientists Prof Rainer Haas, Max von Pettenkofer-Institut of the LMU, and Prof Markus Gerhard, Institute for Medical Microbiology and Immunology of the Technical University of Munich (TUM), have now detected a highly specific and exceptionally strong variant of adhesion: The bacterial surface molecule HopQ binds itself to so-called "Carcinoembryonic Antigen-Related Cell Adhesion Molecules", or CEACAMs for short, inside the stomach.
The molecular toxin injection of Helicobacter pylori
The binding of CEACAMs and HopQ is important for the pathogenic damage of the bacterium: Once bound to CEACAM, Helicobacter pylori can inject the bacterial toxin CagA into the epithelial cells of the gastric mucosa. This secretion system contributes significantly to the development of stomach ulcers and bowel cancer.
New options to preventing or treating infections
Against this backdrop, Prof Markus Gerhard assumes that HopQ could be used diagnostically and therapeutically. In cooperation with PD Dr Bernhard B. Singer, Essen University Hospital, and Prof Han Remaut, VIB in Brussels, Gerhard is currently researching various approaches in order to replace current types of treatment for Helicobacter pylori, due to the side effects. „We already generated a cristal structure of the adhesion molecule HopQ, from which we could deduce the binding domain", says Gerhard. The adhesion of the bacterium to stomach cells could be prevented with a soluble version of HopQ or parts of the protein, and the damaging effects of the germ could potentially be suppressed, as the data in the publication indicate.
Verena Königer, Lea Holsten, Ute Harrison, Benjamin Busch, Eva Loell, Qing Zhao, Daniel A. Bonsor, Alexandra Roth, Arnaud Kengmo-Tchoupa, Stella I. Smith, Susanna Mueller, Eric J. Sundberg, Wolfgang Zimmermann, Wolfgang Fischer, Christof R. Hauck and Rainer Haas:
Helicobacter pylori exploits human CEACAMs via HopQ for adherence and translocation of CagA
Nature Microbiology 2016 doi:10.1038/nmicrobiol.2016.188
Anahita Javaheri, Tobias Kruse, Kristof Moonens, Ayla Debraekeleer, Raquel Mejías-Luque, Isabell Asche, Nicole Tegtmeyer, Behnam Kalali, Nina C. Bach, Stephan A. Sieber, Darryl J. Hill, Verena Königer, Christof R. Hauck, Rainer Haas, Dirk H. Busch, Esther Klaile, Hortense Slevogt, Alexej Schmidt, Steffen Backert, Han Remaut, Bernhard B. Singer and Markus Gerhard:
Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs
Nature Microbiology 2016 doi:10.1038/nmicrobiol.2016.189
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