Helicobacter pylori cag-Type IV Secretion System: Integrin interaction and mechanism of CagA protein translocation

• Applicant: Professor Dr. Rainer Haas
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2010 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 180450754

Helicobacter pylori is a Gram-negative bacterial pathogen, colonizing the gastric mucosa of about 50% of the human population. H. pylori infection is associated with a number of gastroduodenal diseases, including chronic gastritis, peptic ulcers, adenocarcinoma and mucosa-associated-lymphoid tissue (MALT) lymphoma. Certain H. pylori strains carry the cag-pathogenicity island (cag-PAI), which encodes a Type IV Secretion System (T4SS) to deliver the bacterial oncoprotein CagA into the cytoplasm of gastric epithelial cells. The cag- T4SS consists of about 30 proteins, forming a bacterial transmembrane channel and a surface-associated needle-like pilus structure (injectisome). We recently identified CagA (the translocated effector protein) and CagY on the tip of the T4SS pilus, and CagA, CagI and CagY were found to interact with β1 integrin receptors on the host cell surface. In this project we are interested to understand (1) the signaling process and the mechanism for induction of T4SS pilus formation, (2) the precise interaction of the different Cag proteins with the integrin receptor, and (3) the basic mechanism of CagA protein translocation by the H. pylori cag- T4SS. We expect to unravel a completely novel mechanism of protein translocation in a bacterial T4SS and the results might be of importance for many other bacterial pathogens.

• DFG Programme: Research Grants