Functional insight in the biogenesis and specificity of the family of outer membrane porins expressed by the bacterial carcinogen Helicobacter pylori (FWOKN287)

Helicobacter pylori (HP) is an important human pathogen and chronically infects the stomach of up to half the world population, thereby causing chronic gastritis, duodenal ulcers and even gastric cancer. A steady emergence of multiple antibiotic resistant strains poses an important public health threat. The blood group antigen binding adhesin (BabA) of HP binds to fucosylated Lewis b and H type 1 blood group antigens on the surfaces of human gastric epithelial cells. Since the presence of a functional babA gene is strongly correlated with the more virulent type 1 Helicobacter strains, BabA forms a major candidate for novel vaccine and drug developments. BabA is a member of the family of Helicobacter Outer membrane Porins (HOPs) that share an architecture reminiscent of auto-transporter-like proteins. Previously, we could obtain the structure of the BabA surface exposed ectodomain in complex with its human host receptor Lewis b and explain the observed specificity of HP. In this project we aim to determine the insertion pathway of BabA, and HOPs in general, into the outer membrane. Also the full length BabA structure will give valuable information in the HP-human host interaction. Finally, we aim to gain structural and functional insight in receptor binding by the HOP adhesin HopQ, another adhesin from the HOP family that has been the focus of recent work.

Keywords:Helicobacter pylori, biology

Disciplines:Laboratory medicine