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Infection and Immunity, February 2002, p. 665-671, Vol. 70, No. 2
0019-9567/01/$04.00+0     DOI: 70.2.665-671.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Functional Analysis of the Helicobacter pylori cag Pathogenicity Island Reveals Both VirD4-CagA-Dependent and VirD4-CagA-Independent Mechanisms

Matthias Selbach, Stefan Moese, Thomas F. Meyer,* and Steffen Backert

Abteilung Molekulare Biologie, Max-Planck-Institut für Infektionsbiologie, D-10117 Berlin, Germany

Received 13 August 2001/ Returned for modification 16 October 2001/ Accepted 8 November 2001

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.

* Corresponding author. Mailing address: Max-Planck-Institut für Infektionsbiologie, Abt. Molekulare Biologie, Schumannstr. 20/21, D-10117 Berlin, Germany. Phone: 49 30 28 46 0 400. Fax: 49 30 28 46 04 01. E-mail: meyer{at}mpiib-berlin.mpg.de.

Editor: E. I. Tuomanen

Infection and Immunity, February 2002, p. 665-671, Vol. 70, No. 2
0019-9567/01/$04.00+0     DOI: 70.2.665-671.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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