title: Role of the cag-pathogenicity island encoded type IV secretion system in Helicobacter pylori pathogenesis.
abstract: Helicobacter pylori is a very successful human-specific bacterium worldwide. Infections of the stomach with this pathogen can induce pathologies, including chronic gastritis, peptic ulcers and even gastric cancer. Highly virulent H. pylori strains encode the cytotoxin-associated gene (cag)-pathogenicity island, which expresses a type IV secretion system (T4SS). This T4SS forms a syringe-like pilus structure for the injection of virulence factors such as the CagA effector protein into host target cells. This is achieved by a number of T4SS proteins, including CagI, CagL, CagY and CagA, which by itself binds the host cell integrin member β(1) followed by delivery of CagA across the host cell membrane. A role of CagA interaction with phosphatidylserine has also been shown to be important for the injection process. After delivery, CagA becomes phosphorylated by oncogenic tyrosine kinases and mimics a host cell factor for the activation or inactivation of some specific intracellular signalling pathways. We review recent progress aiming to characterize the CagA-dependent and CagA-independent signalling capabilities of the T4SS, which include the induction of membrane dynamics, disruption of cell-cell junctions and actin-cytoskeletal rearrangements, as well as pro-inflammatory, cell cycle-related and anti-apoptotic transcriptional responses. The contribution of these signalling pathways to pathogenesis during H. pylori infections is discussed.
authors.affiliation: School of Biomolecular and Biomedical Sciences, Science Center West, Belfield Campus, University College Dublin, Dublin, Ireland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Tegtmeyer
authors.forename: Silja
authors.initials: S
authors.lastname: Wessler
authors.forename: Steffen
authors.initials: S
authors.lastname: Backert
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000502:physiology*; D001426:Bacterial Proteins / Q000502:physiology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000382:microbiology; D044404:Genomic Islands; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000503:physiopathology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori; C094670:MARK2 protein, human; D019061:src-Family Kinases; D017346:Protein Serine-Threonine Kinases