In Vivo Structures of the Helicobacter pylori cag Type IV Secretion System

The type IV secretion system (T4SS) is a versatile nanomachine that translocates diverse effector molecules between microbes and into eukaryotic cells. Here, using electron cryotomography, we reveal the molecular architecture of the Helicobacter pylori cag T4SS. Although most components are unique to H. pylori, the cag T4SS exhibits remarkable architectural similarity to other T4SSs. Our images revealed that, when H. pylori encounters host cells, the bacterium elaborates membranous tubes perforated by lateral ports. Sub-tomogram averaging of the cag T4SS machinery revealed periplasmic densities associated with the outer membrane, a central stalk, and peripheral wing-like densities. Additionally, we resolved pilus-like rod structures extending from the cag T4SS into the inner membrane, as well as densities within the cytoplasmic apparatus corresponding to a short central barrel surrounded by four longer barrels. Collectively, these studies reveal the structure of a dynamic molecular machine that evolved to function in the human gastric niche. [Display omitted] •H. pylori assemble unusual tube-like appendages when in proximity to gastric cells•Architecture of the cag T4SS is remarkably similar to that of the Legionella dot/icm T4SS•The cag T4SS cytoplasmic apparatus is likely a five-barrel structure Bacteria assemble specialized type IV secretion systems (T4SSs) to inject molecular cargo into target cells. Using electron cryotomography, Chang and Shaffer et al. report the first structure of a cancer-associated T4SS in vivo and describe unique membranous appendages that are produced when H. pylori encounters gastric epithelial cells.