Structural and functional characterization of Helicobacter pylori outer membrane adhesins and their role in host adaption

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 Proteins (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 unravel how the highly diverse BabA sequence correlates with adaptation to the human host. Also we aim to determine the insertion pathway of BabA into the outer membrane and the full length BabA structure will shed light on the orientation of the BabA ectodomain on the HP surface, and thus 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.