Previous Article | Next Article 
Journal of Clinical Microbiology, April 1998, p. 944-948, Vol. 36, No. 4
0095-1137/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Diversity of Helicobacter pylori vacA and
cagA Genes and Relationship to VacA and CagA Protein
Expression, Cytotoxin Production, and Associated Diseases
Jochen
Rudi,1,*
Christof
Kolb,1
Matthias
Maiwald,2
Dirk
Kuck,1
Andreas
Sieg,1
Peter R.
Galle,1 and
Wolfgang
Stremmel1
Department of Medicine, Division of
Gastroenterology,1 and
Institute of
Microbiology,2 University of Heidelberg,
Heidelberg, Germany
Received 27 August 1997/Returned for modification 17 November
1997/Accepted 5 January 1998
The vacuolating cytotoxin and the cytotoxin-associated protein,
encoded by vacA and cagA, respectively, are
important virulence determinants of Helicobacter pylori.
Sixty-five H. pylori strains were isolated from dyspeptic
patients (19 with peptic ulcer disease, 43 with chronic gastritis, and
3 with gastric cancer) and studied for differences in the
vacA and cagA genes and their relationship to
VacA and CagA expression, cytotoxin activity, and the clinical outcome
of infection. By PCR, fifty-four (83.1%) of 65 strains had the
vacA signal sequence genotype s1 and only 10 (15.4%) had the type s2. After primer modification, the vacA
middle-region types m1 and m2 were detected in 24 (36.9%) and 41 (63.1%) strains, respectively. The combinations s1-m2 (31 [47.7%])
and s1-m1 (23 [35.4%]) occurred more frequently than s2-m2 (10 [15.4%]) (P = 0.01). No strain with the combination
s2-m1 was found. All 19 patients with peptic ulcers harbored type s1
strains, in contrast to 32 (74.4%) of 43 patients with gastritis
(P = 0.02). The vacA genotype s1 was
associated with the presence of cagA (P < 0.0001), VacA expression (P < 0.0001), and cytotoxin
activity (P = 0.003). The cagA gene was
detectable in 48 (73.8%) of 65 isolates and present in 16 (84.2%) of
19 ulcer patients and 29 (67.4%) of 43 patients with gastritis
(P = 0.17). The vacA genotypes of German H. pylori isolates are identical to those previously
reported. H. pylori strains of vacA type s1 are
associated with the occurrence of peptic ulceration and the presence of
cagA, cytotoxin activity, and VacA expression.
*
Corresponding author. Mailing address: Department of
Medicine, Division of Gastroenterology, University of Heidelberg,
Bergheimerstr. 58, 69115 Heidelberg, Germany. Phone: 49 6221-568611. Fax: 49 6221-565255. E-mail:
jochen_rudi{at}krzmail.krz.uni-heidelberg.de
Journal of Clinical Microbiology, April 1998, p. 944-948, Vol. 36, No. 4
0095-1137/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Jones, K. R., Joo, Y. M., Jang, S., Yoo, Y.-J., Lee, H. S., Chung, I.-S., Olsen, C. H., Whitmire, J. M., Merrell, D. S., Cha, J.-H.
(2009). Polymorphism in the CagA EPIYA Motif Impacts Development of Gastric Cancer. J. Clin. Microbiol.
47: 959-968
[Abstract]
[Full Text]
-
Takeshima, E., Tomimori, K., Teruya, H., Ishikawa, C., Senba, M., D'Ambrosio, D., Kinjo, F., Mimuro, H., Sasakawa, C., Hirayama, T., Fujita, J., Mori, N.
(2009). Helicobacter pylori-Induced Interleukin-12 p40 Expression. Infect. Immun.
77: 1337-1348
[Abstract]
[Full Text]
-
Argent, R. H., Hale, J. L., El-Omar, E. M., Atherton, J. C.
(2008). Differences in Helicobacter pylori CagA tyrosine phosphorylation motif patterns between western and East Asian strains, and influences on interleukin-8 secretion. J Med Microbiol
57: 1062-1067
[Abstract]
[Full Text]
-
Hussein, N. R., Mohammadi, M., Talebkhan, Y., Doraghi, M., Letley, D. P., Muhammad, M. K., Argent, R. H., Atherton, J. C.
(2008). Differences in Virulence Markers between Helicobacter pylori Strains from Iraq and Those from Iran: Potential Importance of Regional Differences in H. pylori-Associated Disease. J. Clin. Microbiol.
46: 1774-1779
[Abstract]
[Full Text]
-
Emilia, G., Luppi, M., Zucchini, P., Morselli, M., Potenza, L., Forghieri, F., Volzone, F., Jovic, G., Leonardi, G., Donelli, A., Torelli, G.
(2007). Helicobacter pylori infection and chronic immune thrombocytopenic purpura: long-term results of bacterium eradication and association with bacterium virulence profiles. Blood
110: 3833-3841
[Abstract]
[Full Text]
-
Wen, S., Velin, D., Felley, C. P., Du, L., Michetti, P., Pan-Hammarstrom, Q.
(2007). Expression of Helicobacter pylori Virulence Factors and Associated Expression Profiles of Inflammatory Genes in the Human Gastric Mucosa. Infect. Immun.
75: 5118-5126
[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]
-
Kim, J. M., Kim, J. S., Lee, J. Y., Kim, Y.-J., Youn, H.-J., Kim, I. Y., Chee, Y. J., Oh, Y.-K., Kim, N., Jung, H. C., Song, I. S.
(2007). Vacuolating Cytotoxin in Helicobacter pylori Water-Soluble Proteins Upregulates Chemokine Expression in Human Eosinophils via Ca2+ Influx, Mitochondrial Reactive Oxygen Intermediates, and NF-{kappa}B Activation. Infect. Immun.
75: 3373-3381
[Abstract]
[Full Text]
-
Panayotopoulou, E. G., Sgouras, D. N., Papadakos, K., Kalliaropoulos, A., Papatheodoridis, G., Mentis, A. F., Archimandritis, A. J.
(2007). Strategy To Characterize the Number and Type of Repeating EPIYA Phosphorylation Motifs in the Carboxyl Terminus of CagA Protein in Helicobacter pylori Clinical Isolates. J. Clin. Microbiol.
45: 488-495
[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]
-
Zhang, Y., Argent, R. H., Letley, D. P., Thomas, R. J., Atherton, J. C.
(2005). Tyrosine Phosphorylation of CagA from Chinese Helicobacter pylori Isolates in AGS Gastric Epithelial Cells. J. Clin. Microbiol.
43: 786-790
[Abstract]
[Full Text]
-
Argent, R. H., Zhang, Y., Atherton, J. C.
(2005). Simple Method for Determination of the Number of Helicobacter pylori CagA Variable-Region EPIYA Tyrosine Phosphorylation Motifs by PCR. J. Clin. Microbiol.
43: 791-795
[Abstract]
[Full Text]
-
Henderson, I. R., Navarro-Garcia, F., Desvaux, M., Fernandez, R. C., Ala'Aldeen, D.
(2004). Type V Protein Secretion Pathway: the Autotransporter Story. Microbiol. Mol. Biol. Rev.
68: 692-744
[Abstract]
[Full Text]
-
Saribasak, H., Salih, B. A., Yamaoka, Y., Sander, E.
(2004). Analysis of Helicobacter pylori Genotypes and Correlation with Clinical Outcome in Turkey. J. Clin. Microbiol.
42: 1648-1651
[Abstract]
[Full Text]
-
Zhou, J., Zhang, J., Xu, C., He, L.
(2004). cagA genotype and variants in Chinese Helicobacter pylori strains and relationship to gastroduodenal diseases. J Med Microbiol
53: 231-235
[Abstract]
[Full Text]
-
Willhite, D. C., Cover, T. L., Blanke, S. R.
(2003). Cellular Vacuolation and Mitochondrial Cytochrome c Release Are Independent Outcomes of Helicobacter pylori Vacuolating Cytotoxin Activity That Are Each Dependent on Membrane Channel Formation. J. Biol. Chem.
278: 48204-48209
[Abstract]
[Full Text]
-
Letley, D. P., Rhead, J. L., Twells, R. J., Dove, B., Atherton, J. C.
(2003). Determinants of Non-toxicity in the Gastric Pathogen Helicobacter pylori. J. Biol. Chem.
278: 26734-26741
[Abstract]
[Full Text]
-
Marchildon, P. A., Sugiyama, T., Fukada, Y., Peacock, J. S., Asaka, M., Shimoyama, T., Graham, D. Y.
(2003). Evaluation of the Effects of Strain-Specific Antigen Variation on the Accuracy of Serologic Diagnosis of Helicobacter pylori Infection. J. Clin. Microbiol.
41: 1480-1485
[Abstract]
[Full Text]
-
Cao, P., Cover, T. L.
(2002). Two Different Families of hopQ Alleles in Helicobacter pylori. J. Clin. Microbiol.
40: 4504-4511
[Abstract]
[Full Text]
-
FIGUEROA, G., TRONCOSO, M., TOLEDO, M.S., FAUNDEZ, G., ACUNA, R.
(2002). Prevalence of serum antibodies to Helicobacter pylori VacA and CagA and gastric diseases in Chile. J Med Microbiol
51: 300-304
[Abstract]
[Full Text]
-
McClain, M. S., Cao, P., Iwamoto, H., Vinion-Dubiel, A. D., Szabo, G., Shao, Z., Cover, T. L.
(2001). A 12-Amino-Acid Segment, Present in Type s2 but Not Type s1 Helicobacter pylori VacA Proteins, Abolishes Cytotoxin Activity and Alters Membrane Channel Formation. J. Bacteriol.
183: 6499-6508
[Abstract]
[Full Text]
-
Ishii, E., Yokota, K., Sugiyama, T., Fujinaga, Y., Ayada, K., Hokari, I., Hayashi, S., Hirai, Y., Asaka, M., Oguma, K.
(2001). Immunoglobulin G1 Antibody Response to Helicobacter pylori Heat Shock Protein 60 Is Closely Associated with Low-Grade Gastric Mucosa-Associated Lymphoid Tissue Lymphoma. CVI
8: 1056-1059
[Abstract]
[Full Text]
-
Vinion-Dubiel, A. D., McClain, M. S., Cao, P., Mernaugh, R. L., Cover, T. L.
(2001). Antigenic Diversity among Helicobacter pylori Vacuolating Toxins. Infect. Immun.
69: 4329-4336
[Abstract]
[Full Text]
-
Kidd, M, Lastovica, A J, Atherton, J C, Louw, J A
(2001). Conservation of the cag pathogenicity island is associated with vacA alleles and gastroduodenal disease in South African Helicobacter pylori isolates. Gut
49: 11-17
[Abstract]
[Full Text]
-
Suda, Y., Kim, Y.-M., Ogawa, T., Yasui, N., Hasegawa, Y., Kashihara, W., Shimoyama, T., Aoyama, K., Nagata, K., Tamura, T., Kusumoto, S.
(2001). Chemical structure and biological activity of a lipid A component from Helicobacter pylori strain 206. Innate Immunity
7: 95-104
[Abstract]
-
Rota, C. A., Pereira-Lima, J. C., Blaya, C., Nardi, N. B.
(2001). Consensus and Variable Region PCR Analysis of Helicobacter pylori 3' Region of cagA Gene in Isolates from Individuals with or without Peptic Ulcer. J. Clin. Microbiol.
39: 606-612
[Abstract]
[Full Text]
-
Enroth, H., Kraaz, W., Engstrand, L., Nyrén, O., Rohan, T.
(2000). Helicobacter pylori Strain Types and Risk of Gastric Cancer: A Case-Control Study. Cancer Epidemiol. Biomarkers Prev.
9: 981-985
[Abstract]
[Full Text]
-
Vaucher, C., Janvier, B., Nousbaum, J.-B., Grignon, B., Pezennec, L., Robaszkiewicz, M., Gouerou, H., Picard, B., Fauchere, J.-L.
(2000). Antibody Response of Patients with Helicobacter pylori-Related Gastric Adenocarcinoma: Significance of Anti-CagA Antibodies. CVI
7: 463-467
[Abstract]
[Full Text]
-
BLASER, M J
(1999). Allelic variation in Helicobacter pylori: progress but no panacea. Gut
45: 477-478
[Full Text]
-
Kidd, M, Lastovica, A J, Atherton, J C, Louw, J A
(1999). Heterogeneity in the Helicobacter pylori vacA and cagA genes: association with gastroduodenal disease in South Africa?. Gut
45: 499-502
[Abstract]
[Full Text]
-
Atherton, J. C., Cover, T. L., Twells, R. J., Morales, M. R., Hawkey, C. J., Blaser, M. J.
(1999). Simple and Accurate PCR-Based System for Typing Vacuolating Cytotoxin Alleles of Helicobacter pylori. J. Clin. Microbiol.
37: 2979-2982
[Abstract]
[Full Text]
-
Domingo, D., Alarcón, T., Prieto, N., Sánchez, I., López-Brea;, M., Rudi, J., Stremmel, W.
(1999). cagA and vacA Status of Spanish Helicobacter pylori Clinical Isolates. J. Clin. Microbiol.
37: 2113-2114
[Full Text]
-
Donati, M., Storni, E., D'Apote, L., Moreno, S., Tucci, A., Poli, L., Cevenini, R.
(1999). PCR-Based Restriction Pattern Typing of the vacA Gene Provides Evidence for a Homogeneous Group among Helicobacter pylori Strains Associated with Peptic Ulcer Disease. J. Clin. Microbiol.
37: 912-915
[Abstract]
[Full Text]
-
Evans, D. G., Queiroz, D. M. M., Mendes, E. N., Evans, D. J. Jr.
(1998). Helicobacter pylori cagA Status and s and m Alleles of vacA in Isolates from Individuals with a Variety of H. pylori-Associated Gastric Diseases. J. Clin. Microbiol.
36: 3435-3437
[Abstract]
[Full Text]