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Role of Helicobacter pylori CagL in modulating gastrin expression
  1. Timothy L Cover1,2,3
  1. 1Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
  2. 2Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
  3. 3Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA
  1. Correspondence to Timothy L Cover, Division of Infectious Diseases, A2200 MCN, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; timothy.l.cover{at}vanderbilt.edu

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Helicobacter pylori is a Gram-negative bacterium that is highly adapted for persistent colonisation of the human stomach. Although most H pylori-infected people remain asymptomatic, the presence of this organism is a risk factor for gastric adenocarcinoma, peptic ulcer disease and gastric lymphoma. There is a high level of genetic heterogeneity among H pylori strains and the risk of gastric disease is determined, in part, by characteristics of the H pylori strain(s) with which a person is infected.1 One of the most extensively studied genetic features of disease-associated H pylori strains is the cag pathogenicity island (PAI). This 40 kb region of chromosomal DNA, comprising about 27 genes, may be present, incomplete or absent in H pylori strains.

CagA, the first cag PAI-encoded protein to be studied in detail, is a highly antigenic protein that is translocated into gastric epithelial cells. Within gastric epithelial cells, CagA undergoes phosphorylation by host cell tyrosine kinases and interacts with multiple host proteins, leading to cytoskeletal rearrangements, disruption of cellular junctions, altered cellular adhesion and polarity and increased cell proliferation. Experiments in animal models indicate that CagA has an important role in the pathogenesis of gastric cancer and therefore, CagA has been termed a bacterial oncoprotein.2 CagA is translocated into host cells by a process that requires about 17 genes within the cag PAI, several of which are homologous to genes encoding components of type IV secretion systems (T4SS) in other Gram-negative bacterial …

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