The role of outer membrane proteins HopI and HopQ of Helicobacter pylori in blocking CagA toxin translocation into gastric cells upon multiple strain infections.

• Applicant: Dr. Luisa Fernanda Jiménez Soto
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 257731603

Helicobacter pylori is a human pathogen infecting the stomachs of almost 50% of the human population. Its presence is associated with gastric pathologies. Infections of a single host with multiple strains of Helicobacter pylori are not unusual, especially in developing countries. A major pathogenicity factor of H. pylori is the presence of the cag-Type IV secretion system (cag-T4SS), a syringe-like molecular appendage on the bacterial surface, which is able to directly inject the bacterial cytotoxin-associated antigen A (CagA), also considered as a bacterial oncoprotein, into gastric epithelial cells. Injection of CagA interferes with cell signaling and is associated with more severe pathology, including gastric cancer. By performing H. pylori co-infections experiments using multiple H. pylori strains in cell culture infection assays, we discovered a mechanism in the host cell that blocks the effective delivery of the CagA toxin into the cell. The bacterial triggers could be identified as the H. pylori outer membrane proteins (OMPs) HopI and HopQ . In the proposed project we aim to address two main questions: How do HopI and HopQ trigger the resistance to the injection of CagA toxin and what are the specific requirements of the cell membrane for injection of CagA.

• DFG Programme: Research Grants