DOI: 10.1128/iai.72.2.1043-1056.2004. Functional Analysis of the<i>cag</i>Pathogenicity Island in<i>Helicobacter pylori</i>Isolates from Patients with Gastritis, Peptic Ulcer, and Gastric Cancer

Functional Analysis of thecagPathogenicity Island inHelicobacter pyloriIsolates from Patients with Gastritis, Peptic Ulcer, and Gastric Cancer

10.1128/iai.72.2.1043-1056.2004

Crossref journal-article

American Society for Microbiology

Infection and Immunity (235)

Abstract

ABSTRACTHelicobacter pyloriis the causative agent of a variety of gastric diseases, but the clinical relevance of bacterial virulence factors is still controversial. Virulent strains carrying thecagpathogenicity island (cagPAI) are thought to be key players in disease development. Here, we have comparedcagPAI-dependent in vitro responses inH. pyloriisolates 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 thesecagPAI-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 ofcagPAI presence and functionality with histopathological findings in gastritis, peptic ulcer, and gastric cancer patients, thus emphasizing the importance of thecagPAI for the pathogenicity ofH. pylori. Nevertheless, we found no significant association of the specificH. 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.

Bibliography

Backert, S., Schwarz, T., Miehlke, S., Kirsch, C., Sommer, C., Kwok, T., Gerhard, M., Goebel, U. B., Lehn, N., Koenig, W., & Meyer, T. F. (2004). Functional Analysis of thecagPathogenicity Island inHelicobacter pyloriIsolates from Patients with Gastritis, Peptic Ulcer, and Gastric Cancer. Infection and Immunity, 72(2), 1043â1056.

Authors 11

Steffen Backert (first)
Tobias Schwarz (additional)
Stephan Miehlke (additional)
Christian Kirsch (additional)
Christian Sommer (additional)
Terry Kwok (additional)
Markus Gerhard (additional)
Ulf B. Goebel (additional)
Norbert Lehn (additional)
Wolfgang Koenig (additional)
Thomas F. Meyer (additional)

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Dates

Type	When
Created	21 years, 7 months ago (Jan. 24, 2004, 6:46 p.m.)
Deposited	1 year, 7 months ago (Jan. 11, 2024, 7:34 p.m.)
Indexed	1 month, 2 weeks ago (July 11, 2025, 9:22 p.m.)
Issued	21 years, 6 months ago (Feb. 1, 2004)
Published	21 years, 6 months ago (Feb. 1, 2004)
Published Print	21 years, 6 months ago (Feb. 1, 2004)

Funders 0

None

BibTeX

@article{Backert_2004, title={Functional Analysis of thecagPathogenicity Island inHelicobacter pyloriIsolates from Patients with Gastritis, Peptic Ulcer, and Gastric Cancer}, volume={72}, ISSN={1098-5522}, url={http://dx.doi.org/10.1128/iai.72.2.1043-1056.2004}, DOI={10.1128/iai.72.2.1043-1056.2004}, number={2}, journal={Infection and Immunity}, publisher={American Society for Microbiology}, author={Backert, Steffen and Schwarz, Tobias and Miehlke, Stephan and Kirsch, Christian and Sommer, Christian and Kwok, Terry and Gerhard, Markus and Goebel, Ulf B. and Lehn, Norbert and Koenig, Wolfgang and Meyer, Thomas F.}, year={2004}, month=feb, pages={1043–1056} }

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