Functional Analysis of the
cag
Pathogenicity Island in
Helicobacter pylori
Isolates from Patients with Gastritis, Peptic Ulcer, and Gastric Cancer
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Published:2004-02
Issue:2
Volume:72
Page:1043-1056
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ISSN:0019-9567
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Container-title:Infection and Immunity
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language:en
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Short-container-title:Infect Immun
Author:
Backert Steffen1, Schwarz Tobias2, Miehlke Stephan3, Kirsch Christian3, Sommer Christian2, Kwok Terry1, Gerhard Markus4, Goebel Ulf B.5, Lehn Norbert6, Koenig Wolfgang1, Meyer Thomas F.2
Affiliation:
1. Department of Medical Microbiology, Otto von Guericke University, D-39120 Magdeburg 2. Department of Molecular Biology, Max Planck Institute for Infection Biology 3. Medical Department I, Technical University Hospital, D-01307 Dresden 4. Laboratory of Molecular Gastroenterology, II Medical Department, Klinikum rechts der Isar, Technical University of Munich, D-81675 Munich 5. Institute for Microbiology and Hygiene, Humboldt University, D-10117 Berlin 6. Institute for Medical Microbiology, University of Regensburg, D-93053 Regensburg, Germany
Abstract
ABSTRACT
Helicobacter pylori
is the causative agent of a variety of gastric diseases, but the clinical relevance of bacterial virulence factors is still controversial. Virulent strains carrying the
cag
pathogenicity island (
cag
PAI) are thought to be key players in disease development. Here, we have compared
cag
PAI-dependent in vitro responses in
H. pylori
isolates obtained from 75 patients with gastritis, peptic ulcer, and gastric cancer (
n
= 25 in each group). AGS gastric epithelial cells were infected with each strain and assayed for (i) CagA expression, (ii) translocation and tyrosine phosphorylation of CagA, (iii) c-Src inactivation, (iv) cortactin dephosphorylation, (v) induction of actin cytoskeletal rearrangements associated with cell elongation, (vi) induction of cellular motility, and (vii) secretion of interleukin-8. Interestingly, we found high but similar prevalences of all of these
cag
PAI-dependent host cell responses (ranging from 56 to 80%) among the various groups of patients. This study revealed CagA proteins with unique features, CagA subspecies of various sizes, and new functional properties for the phenotypic outcomes. We further showed that induction of AGS cell motility and elongation are two independent processes. Our data corroborate epidemiological studies, which indicate a significant association of
cag
PAI presence and functionality with histopathological findings in gastritis, peptic ulcer, and gastric cancer patients, thus emphasizing the importance of the
cag
PAI for the pathogenicity of
H. pylori
. Nevertheless, we found no significant association of the specific
H. pylori
-induced responses with any particular patient group. This may indicate that the determination of disease development is highly complex and involves multiple bacterial and/or host factors.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
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