[The type IV secretion system encoded by the cag PAI of Helicobacter pylori]

Helicobacter pylori is a human-specific gastric pathogen that colonizes over half the world's population. Infection with this bacterium is associated with a spectrum of gastric pathologies ranging from mild gastritis to peptic ulcers and gastric cancer. A strong predictor of severe disease outcome is infection with a bacterial strain harbouring the cag (cytotoxin associated gene) pathogenicity island (PAI), a 40 kb stretch of DNA that encodes homologues of several components of a type IV secretion system (TFSS). One gene within the cag PAI, cagA, has been shown to encode a substrate for the TFSS which is translocated into host cells, inducing the dephosphrylation of host cell proteins and leading to changes in the morphology or shape of AGS gastric epithelial cells. Furthermore, the TFSS is involved in the induction of proinflammatory cytokines. It appeears to play a key role in H. pylori pathogenesis. Very little is known about the H. pylori cag PAI-encoded TFSS, the expression of Cag proteins in H. pylori, and the functions of individual proteins encoded by the cag PAI. Only by exploring the mechanistic details of the interplay between H. pylori and eukaryotic cells can we endeavour to understand how these cellular interactions play out at the tissue and organismal level during the lifelong coexistence of bacterium and host.