Details

Autor(en) / Beteiligte

• Tegtmeyer, Nicole
• Wessler, Silja
• Backert, Steffen

Titel

Role of the cag-pathogenicity island encoded type IV secretion system in Helicobacter pylori pathogenesis

Ist Teil von

• The FEBS journal, 2011-04, Vol.278 (8), p.1190-1202

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2011

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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 β₁ 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.