Functional Analysis of the
Helicobacter pylori cag
Pathogenicity Island Reveals Both VirD4-CagA-Dependent and VirD4-CagA-Independent Mechanisms
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Published:2002-02
Issue:2
Volume:70
Page:665-671
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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:
Selbach Matthias1, Moese Stefan1, Meyer Thomas F.1, Backert Steffen1
Affiliation:
1. Abteilung Molekulare Biologie, Max-Planck-Institut für Infektionsbiologie, D-10117 Berlin, Germany
Abstract
ABSTRACT
The type IV secretion machinery encoded by the
cag
pathogenicity island (PAI) of
Helicobacter pylori
has been implicated in a series of host responses during infection. Here, we analyzed the function of 12
cag
PAI genes from both
cag
I and
cag
II loci, including the complete
virB/D
complex (
virB4, virB7, virB8, virB9, virB10, virB11
, and
virD4
). We monitored interleukin-8 (IL-8) secretion, CagA translocation and tyrosine phosphorylation, and induction of a scattering (“hummingbird”) phenotype upon
H. pylori
infection of AGS gastric epithelial cells. For the first time, we have complemented individual
cag
PAI gene knockout mutants with their intact genes expressed from a shuttle vector and showed that complemented CagA and VirD4 restored wild-type function. Our results demonstrate that phenotypic changes and phosphorylation of CagA depended on all
virB/D
genes and several other genes of the
cag
PAI. Induction of IL-8 secretion depended largely on the same set of genes but was independent of CagA and VirD4. Thus, CagA translocation and induction of IL-8 secretion are regulated by VirD4-CagA-dependent and VirD4-CagA-independent mechanisms, respectively. The function of VirD4 as a possible adapter protein which guides CagA into the type IV secretion channel is presented in a model.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Reference44 articles.
1. Akopyants, N. S., S. W. Clifton, D. Kersulyte, J. E. Crabtree, B. E. Youree, C. A. Reece, N. O. Bukanov, E. S. Drazek, B. A. Roe, and D. E. Berg. 1998. Analyses of the cag pathogenicity island of Helicobacter pylori. Mol. Microbiol.28:37-53. 2. Alm, R. A., L. S. Ling, D. T. Moir, B. L. King, E. D. Brown, P. C. Doig, D. R. Smith, B. Noonan, B. C. Guild, B. L. deJonge, G. Carmel, P. J. Tummino, A. Caruso, M. Uria-Nickelsen, D. M. Mills, C. Ives, R. Gibson, D. Merberg, S. D. Mills, Q. Jiang, D. E. Taylor, G. F. Vovis, and T. J. Trust. 1999. Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature397:176-180. 3. Asahi, M., T. Azuma, S. Ito, Y. Ito, H. Suto, Y. Nagai, M. Tsubokawa, Y. Tohyama, S. Maeda, M. Omata, T. Suzuki, and C. Sasakawa. 2000. Helicobacter pylori CagA protein can be tyrosine phosphorylated in gastric epithelial cells. J. Exp. Med.191:593-602. 4. Implication of the Structure of the
Helicobacter pylori cag
Pathogenicity Island in Induction of Interleukin-8 Secretion 5. Backert, S., S. Moese, M. Selbach, V. Brinkmann, and T. F. Meyer. 2001. Phosphorylation of tyrosine 972 of the Helicobacter pylori CagA protein is essential for induction of a scattering phenotype in gastric epithelial cells. Mol. Microbiol.42:631-644.
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