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

Authors

  • Nicole Tegtmeyer,

    1.  School of Biomolecular and Biomedical Sciences, Science Center West, Belfield Campus, University College Dublin, Ireland
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  • Silja Wessler,

    1.  Department of Molecular Biology, Division of Microbiology, Paris-Lodron University of Salzburg, Austria
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  • Steffen Backert

    1.  School of Biomolecular and Biomedical Sciences, Science Center West, Belfield Campus, University College Dublin, Ireland
    2.  Institute for Medical Microbiology, Otto von Guericke University Magdeburg, Germany
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S. Backert, University College Dublin, Belfield Campus, School of Biomolecular and Biomedical Science, Science Center West, Dublin-4, Ireland
Fax: +353 1 716 1183
Tel: +353 1 716 2155
E-mail: steffen.backert@ucd.ie

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 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.

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