The Helicobacter pylori Cag Pathogenicity Island Protein Cag1 is Associated with the Function of T4SS

The human pathogen Helicobacter pylori is involved in gastric diseases ranging from gastritis to gastric cancer. Virulent strains harboring the cag pathogenicity island (cag PAI) which encode a Type IV Secretion System (T4SS) can induce pro-inflammatory cytokines such as interleukin-8 and deliver their major effector proteins CagA into the gastric cells. While a subset of cag PAI genes have been identified to be the homologues of T4SS genes from Agrobacterium tumefaciens, a majority have unknown functions. We have identified one of such proteins, Cag1, which was predicted to be a non-classically secreted and virulent protein. Our results showed that Cag1 is a membrane-associated protein essential for the induction of multiple cytokine secretions, and cag1-deficient mutant has partial influence on CagA translocation; while the protein itself was not injected into host cells. Our data indicated that Cag1 is located in the bacterial membrane and is associated with the function of T4SS.