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

FEBS J. 2011 Apr;278(8):1190-202. doi: 10.1111/j.1742-4658.2011.08035.x. Epub 2011 Feb 25.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, Bacterial / physiology*
  • Bacterial Proteins / physiology*
  • Cells, Cultured
  • Epithelial Cells / microbiology
  • Genomic Islands*
  • Gerbillinae
  • Helicobacter Infections / physiopathology
  • Helicobacter pylori / pathogenicity*
  • Host-Pathogen Interactions
  • Humans
  • Mice
  • Mice, Transgenic
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism
  • Signal Transduction / physiology
  • src-Family Kinases / metabolism

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • cagA protein, Helicobacter pylori
  • MARK2 protein, human
  • src-Family Kinases
  • Protein-Serine-Threonine Kinases