This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Backert, S. Articles by Meyer, T. F. Search for Related Content PubMed PubMed Citation Articles by Backert, S. Articles by Meyer, T. F.

 Previous Article  |  Next Article 

Infection and Immunity, February 2004, p. 1043-1056, Vol. 72, No. 2
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.2.1043-1056.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Functional Analysis of the cag Pathogenicity Island in Helicobacter pylori Isolates from Patients with Gastritis, Peptic Ulcer, and Gastric Cancer

Department of Medical Microbiology, Otto von Guericke University, D-39120 Magdeburg,¹ Department of Molecular Biology, Max Planck Institute for Infection Biology,² Institute for Microbiology and Hygiene, Humboldt University, D-10117 Berlin,⁵ Medical Department I, Technical University Hospital, D-01307 Dresden,³ Laboratory of Molecular Gastroenterology, II Medical Department, Klinikum rechts der Isar, Technical University of Munich, D-81675 Munich,⁴ Institute for Medical Microbiology, University of Regensburg, D-93053 Regensburg, Germany⁶

Received 28 August 2003/ Returned for modification 29 September 2003/ Accepted 14 October 2003

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 (cagPAI) are thought to be key players in disease development. Here, we have compared cagPAI-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 cagPAI-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 cagPAI presence and functionality with histopathological findings in gastritis, peptic ulcer, and gastric cancer patients, thus emphasizing the importance of the cagPAI 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.

Editor: D. L. Burns

This article has been cited by other articles:

• Lai, C.-H., Chang, Y.-C., Du, S.-Y., Wang, H.-J., Kuo, C.-H., Fang, S.-H., Fu, H.-W., Lin, H.-H., Chiang, A.-S., Wang, W.-C. (2008). Cholesterol Depletion Reduces Helicobacter pylori CagA Translocation and CagA-Induced Responses in AGS Cells. Infect. Immun. 76: 3293-3303 [Abstract] [Full Text]  
• Ding, S.-Z., Minohara, Y., Fan, X. J., Wang, J., Reyes, V. E., Patel, J., Dirden-Kramer, B., Boldogh, I., Ernst, P. B., Crowe, S. E. (2007). Helicobacter pylori Infection Induces Oxidative Stress and Programmed Cell Death in Human Gastric Epithelial Cells. Infect. Immun. 75: 4030-4039 [Abstract] [Full Text]  
• Reyes-Leon, A., Atherton, J. C., Argent, R. H., Puente, J. L., Torres, J. (2007). Heterogeneity in the Activity of Mexican Helicobacter pylori Strains in Gastric Epithelial Cells and Its Association with Diversity in the cagA Gene. Infect. Immun. 75: 3445-3454 [Abstract] [Full Text]  
• Mitchell, P., Germain, C., Fiori, P. L., Khamri, W., Foster, G. R., Ghosh, S., Lechler, R. I., Bamford, K. B., Lombardi, G. (2007). Chronic Exposure to Helicobacter pylori Impairs Dendritic Cell Function and Inhibits Th1 Development. Infect. Immun. 75: 810-819 [Abstract] [Full Text]  
• Mattar, R., Marques, S. B., Monteiro, M. d. S., dos Santos, A. F., Iriya, K., Carrilho, F. J. (2007). Helicobacter pylori cag pathogenicity island genes: clinical relevance for peptic ulcer disease development in Brazil. J Med Microbiol 56: 9-14 [Abstract] [Full Text]  
• Nambiar, P. R., Kirchain, S. M., Courmier, K., Xu, S., Taylor, N. S., Theve, E. J., Patterson, M. M., Fox, J. G. (2006). Progressive Proliferative and Dysplastic Typhlocolitis in Aging Syrian Hamsters Naturally Infected with Helicobacter spp.: A Spontaneous Model of Inflammatory Bowel Disease. Vet Pathol 43: 2-14 [Abstract] [Full Text]  
• Backert, S., Kwok, T., Konig, W. (2005). Conjugative plasmid DNA transfer in Helicobacter pylori mediated by chromosomally encoded relaxase and TraG-like proteins. Microbiology 151: 3493-3503 [Abstract] [Full Text]  
• Bauer, B., Moese, S., Bartfeld, S., Meyer, T. F., Selbach, M. (2005). Analysis of Cell Type-Specific Responses Mediated by the Type IV Secretion System of Helicobacter pylori. Infect. Immun. 73: 4643-4652 [Abstract] [Full Text]  
• Boonjakuakul, J. K., Canfield, D. R., Solnick, J. V. (2005). Comparison of Helicobacter pylori Virulence Gene Expression In Vitro and in the Rhesus Macaque. Infect. Immun. 73: 4895-4904 [Abstract] [Full Text]  
• Pinto-Santini, D., Salama, N. R. (2005). The Biology of Helicobacter pylori Infection, a Major Risk Factor for Gastric Adenocarcinoma. Cancer Epidemiol. Biomarkers Prev. 14: 1853-1858 [Abstract] [Full Text]  
• Brandt, S., Kwok, T., Hartig, R., Konig, W., Backert, S. (2005). NF-{kappa}B activation and potentiation of proinflammatory responses by the Helicobacter pylori CagA protein. Proc. Natl. Acad. Sci. USA 102: 9300-9305 [Abstract] [Full Text]  
• Kauser, F., Khan, A. A., Hussain, M. A., Carroll, I. M., Ahmad, N., Tiwari, S., Shouche, Y., Das, B., Alam, M., Ali, S. M., Habibullah, C. M., Sierra, R., Megraud, F., Sechi, L. A., Ahmed, N. (2004). The cag Pathogenicity Island of Helicobacter pylori Is Disrupted in the Majority of Patient Isolates from Different Human Populations. J. Clin. Microbiol. 42: 5302-5308 [Abstract] [Full Text]  
• Yuan, J.-P., Li, T., Chen, H.-B., Li, Z.-H., Yang, G.-Z., Hu, B.-Y., Shi, X.-D., Tong, S.-Q., Li, Y.-X., Guo, X.-K. (2004). Analysis of gene expression profile in gastric cancer cells stimulated with Helicobacter pylori isogenic strains. J Med Microbiol 53: 965-974 [Abstract] [Full Text]