Employment of CEA-related cell adhesion molecules (CEACAMs) by Helicobacter pylori

• Applicants: Professor Dr. Markus Gerhard; Privatdozent Dr. Bernhard B. Singer (†)
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens ; Immunology
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 308500591

Helicobacter pylori causes chronic active gastritis and is a major factor in the pathogenesis of duodenal ulcers and gastric ulcers. In addition, the presence of this bacterium is recognized as a risk factor for gastric adenocarcinoma and lymphoma. Adhesion of the bacterium to the gastric epithelium is essential for the establishment of the infection. The specific adhesin-receptor interaction allows the pathogen to tightly bind to its target cells, thereby facilitating colonization of the host tissue. Therefore, the identification and characterization of bacterial adhesins is a major topic in the infection biology of H. pylori. Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) belong to the immunoglobulin (Ig) superfamily of cell surface molecules. Members of the CEACAM family serve as receptors for some Gram-negative bacteria that live on mucosal surfaces of the human body. In our preliminary data, we demonstrate that H. pylori has the capacity to target the CEACAM family of receptors. Among different members of CEACAM family that we studied, H. pylori binds to Human-CEACAM1, CEACAM5 and CEACAM6 but not to Human-CEACAM8. Moreover, we could identify HopQ as the interaction partner of H. pylori with CEACAMs. In the present application, we plan to systematically analyze the biochemical and functional aspects of the HopQ-CEACAM interaction, and its consequences for host cell signaling and responses. These findings will not only further elucidate the complex interaction of this important and highly adopted pathogen with its host, but may also pave the way for novel preventive of therapeutic approaches.

• DFG Programme: Research Grants