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

摘要

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 cag (cytotoxin-associated genes) 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 bind 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 signaling pathways. Here we review recent progress in characterizing CagA-dependent and CagA-independent signalling capabilities of the T4SS which include the induction of membrane dynamics, disruption of cell-to-cell junctions, 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.