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

幽门螺杆菌可引起慢性活动性胃炎，是十二指肠溃疡和胃溃疡的主要致病因素。此外，这种细菌的存在被认为是胃腺癌和淋巴瘤的危险因素。细菌与胃上皮细胞的黏附对感染的建立至关重要。特异的粘附素-受体相互作用使病原体与其靶细胞紧密结合，从而促进宿主组织的定植。因此，细菌粘附素的鉴定和鉴定是幽门螺杆菌感染生物学研究的重要课题。癌胚抗原相关细胞黏附分子(CEACAMs)属于免疫球蛋白(Ig)超家族细胞表面分子。CEACAM家族的成员是一些生活在人体粘膜表面的革兰氏阴性细菌的受体。在我们的初步数据中，我们证明了幽门螺杆菌具有靶向CEACAM受体家族的能力。在我们研究的CEACAM家族的不同成员中，幽门螺杆菌与人-CEACAM1、CEACAM5和CEACAM6结合，而不与人-CEACAM8结合。此外，我们还可以确定HopQ是幽门螺杆菌与CEACAMS的相互作用伙伴。在本申请中，我们计划系统地分析HopQ-CEACAM相互作用的生化和功能方面，以及它对宿主细胞信号和反应的影响。这些发现不仅将进一步阐明这种重要的和高度采用的病原体与其宿主的复杂相互作用，而且还可能为新的预防治疗方法铺平道路。

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.