| Summary: | Colonization of the human stomach by Helicobacter pylori is an important risk factor for development of gastric cancer. The H. pylori cag pathogenicity island (cag PAI) encodes components of a type IV secretion system (T4SS) that translocates the bacterial oncoprotein CagA into gastric epithelial cells, and CagL is a specialized component of the cag T4SS that binds the host receptor α5β1 integrin. Herein, we describe a mass spectrometry-based approach to identify a T4SS subassembly that contains CagL, CagH, and CagI. We demonstrate that these three proteins are required for CagA translocation into host cells and H. pylori-induced IL-8 secretion by gastric epithelial cells; however, these proteins are not homologous to components of T4SSs in other bacterial species. Moreover, we show that these proteins play key roles in biogenesis of T4SS pili at the bacteria-host cell interface. Collectively, these results highlight the important role played by unique constituents of the H. pylori cag T4SS, and illustrate the marked variation that exists among bacterial T4SSs.
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