Translocation of Effector Molecules by the Helicobacter Pylori Type IV Secretion System

Bacteria have evolved specialized nanomachines to deliver microbial cargo across the cell envelope. One versatile translocation apparatus, the type IV secretion system (T4SS), can be strategically deployed to inject macromolecular substrates into target cells. Despite their importance in bacterial pathogenesis, the mechanisms by which the T4SS assembles and transports payload remain largely undefined. The cag T4SS of the gastric bacterium Helicobacter pylori has emerged as a paradigm for understanding how a single molecular machine can translocate a diverse repertoire of lipid, nucleic acid, protein, and polysaccharide cargo into host cells. The goals of this project are to understand the mechanism by which cag T4SS effector molecules are transported across bacterial and eukaryotic membranes to activate components of innate immunity. In addition to providing insight into how H. pylori uses a single nanomachine to augment the risk for gastric disease, the preliminary data generated from these studies will be integrated into R01 applications that interrogate cag T4SS apparatus biogenesis and dynamic steps in substrate translocation. Collectively, these studies will stimulate new basic research directions and will provide important insight into how the T4SS orchestrates the delivery of specific molecular cargo to drive microbial pathogenesis and promote gastric niche colonization.