Identification of novel Helicobacter pylori adhesins and host cell receptors facilitating bacterial access to beta1 integrin and translocation of CagA

• Applicant: Professor Dr. Rainer Haas
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2011 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 195217982

The bacterial pathogen Helicobacter pylori infects the human stomach mucosa, causing chronic gastritis, ulceration and eventually gastric cancer. Pathogenic strains inject the bacterial oncoprotein Cytotoxin-associated antigen A (CagA) into host cells by exploiting beta1 Integrin and carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) as host cell receptors. The gastric epithelium forms a tight layer of epithelial cells strictly connected by junctional complexes (gap junctions, tight junctions, adherence junctions, desmosomes, CEACAMs, etc.). Whereas CEACAMs are usually located at the junctions and on the apical side of the gastric epithelium, beta1 integrins are located at the basolateral side. In this project we want to study the strategies and mechanisms used by H. pylori to make contact to these receptors, especially to the beta1 integrins, under in vivo-like conditions, in order to be able to inject its oncoprotein CagA into these cells. We therefore search for novel bacterial adhesins and host cell receptors and we try to understand the H. pylori adhesin-CEACAM interaction at the molecular level to better understand the signaling events involved. Furthermore, we developed sophisticated novel cell culture models growing as tight monolayers to study these questions. Finally we plan to apply affinity-maturated CEACAM Immunglobulin-like variable (IgV) domains to interfere with CagA translocation in vitro and in vivo in appropriate animal models.

• DFG Programme: Research Grants