Roles of Adhesion to Epithelial Cells in Gastric Colonization by Helicobacter pylori

Helicobacter pylori adherence to host epithelial cells is essential for its survival against the harsh conditions of the stomach and for successful colonization. Adherence of H. pylori is achieved through several related families of outer membrane proteins and proteins of a type IV secretion system (T4SS), which bridge H. pylori to host cells through protein-protein and other protein-ligand interactions. Local environmental conditions such as cell type, available host cell surface proteins and/or ligands, as well as responses by the host immune system force H. pylori to alter expression of these proteins to adapt quickly to the local environment in order to colonize and survive. Some of these host-pathogen interactions appear to function in a "catch-and-release" manner, regulated by reversible binding at varying pH and allowing H. pylori to detach itself from cells or debris sloughed off the gastric epithelial lining in order to return for subsequent productive interactions. Other interactions between bacterial adhesin proteins and host adhesion molecules, however, appear to function as a committed step in certain pathogenic processes, such as translocation of the CagA oncoprotein through the H. pylori T4SS and into host gastric epithelial cells. Understanding these adhesion interactions is critical for devising new therapeutic strategies, as they are responsible for the earliest stage of infection and its maintenance. This review will discuss the expression and regulation of several outer membrane proteins and CagL, how they engage their known host cell protein/ligand targets, and their effects on clinical outcome.