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Role of type IV secretion in Helicobacter pylori pathogenesis

Item Type:Review
Title:Role of type IV secretion in Helicobacter pylori pathogenesis
Creators Name:Backert, S. and Selbach, M.
Abstract:Helicobacter pylori is a highly-successful human-specific gastric pathogen that colonizes more than half the world's population. Infection with this bacterium can induce gastric pathologies ranging from chronic gastritis to peptic ulcers and even cancer. Virulent H. pylori isolates harbour the cag (cytotoxin-associated genes) pathogenicity island, a 40 kb stretch of DNA that encodes components of a type-IV secretion system (T4SS). This T4SS forms a pilus for the injection of virulence factors into host target cells such as the CagA oncoprotein. This is accomplished by a specialised adhesin of the pilus surface, the CagL protein, which binds to and activates host cell integrins for subsequent delivery of CagA across the host cell membrane. Injected CagA becomes tyrosine-phosphorylated by Src and Abl family kinases and mimicks a host cell protein in binding and activation of multiple signalling factors. Here we review the recent advances in the characterization of phosphorylation-dependent and phosphorylation-independent signalling activities of CagA and the T4SS which include the induction of membrane dynamics, actin-cytoskeletal rearrangements and the disruption of cell-to-cell junctions as well as proliferative, pro-inflammatory and anti-apoptotic nuclear responses. The contribution of these signalling cascades to H. pylori pathogenesis is discussed.
Keywords:Signalling, Inflammation, Actin Cytoskeleton, Molecular Pathogenesis, Cancer, Animals
Source:Cellular Microbiology
Publisher:Blackwell Publishing
Page Range:1573-1581
Date:August 2008
Additional Information:The definitive version is available at www.blackwell-synergy.com
Official Publication:https://doi.org/10.1111/j.1462-5822.2008.01156.x
PubMed:View item in PubMed

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