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Clinical relevance of cagPAI intactness in Helicobacter pylori isolates from Vietnam

  • L. T. Nguyen
  • T. Uchida
  • Y. Tsukamoto
  • T. D. Trinh
  • L. Ta
  • H. B. Mai
  • H. S. Le
  • D. Q. D. Ho
  • H. H. Hoang
  • T. Matsuhisa
  • T. Okimoto
  • M. Kodama
  • K. Murakami
  • T. Fujioka
  • Y. Yamaoka
  • M. Moriyama
Article

Abstract

The purpose of this paper is to investigate the relationship between clinical outcome and the intactness of cagPAI in Helicobacter pylori strains from Vietnam. The presence or absence of 30 cagPAI genes was investigated by polymerase chain reaction (PCR) and dot-blotting. H. pylori-induced interleukin-8 secretion and hummingbird phenotype, and H. pylori adhesion to gastric epithelial cells were examined. The serum concentration of pepsinogen 1, pepsinogen 2, and gastrin was also measured in all patients. cagPAI was present in all 103 Vietnamese H. pylori isolates, of which 91 had intact cagPAI and 12 contained only a part of cagPAI. Infection with the partial cagPAI strains was less likely to be associated with peptic ulcer and chronic gastric mucosal inflammation than infection with strains possessing intact cagPAI. The partial cagPAI strains lacked almost all ability to induce interleukin-8 secretion and the hummingbird phenotype in gastric cells. Their adhesion to epithelial cells was significantly decreased in comparison with intact cagPAI strains. Moreover, for the first time, we found an association between cagPAI status and the serum concentration of pepsinogens 1 and 2 in infected patients. H. pylori strains with internal deletion within cagPAI are less virulent and, thus, less likely to be associated with severe clinical outcomes.

Keywords

cagA Gastric Epithelial Cell Pylorus Strain Pylorus Isolate Gastric Mucosal Atrophy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgment

We thank Mrs. Yoko Kudou for her technical assistance.

References

  1. 1.
    Peek RM Jr, Blaser MJ (2002) Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat Rev Cancer 2:28–37CrossRefPubMedGoogle Scholar
  2. 2.
    Suerbaum S, Michetti P (2002) Helicobacter pylori infection. N Engl J Med 347:1175–1186CrossRefPubMedGoogle Scholar
  3. 3.
    Ernst PB, Peura DA, Crowe SE (2006) The translation of Helicobacter pylori basic research to patient care. Gastroenterology 130:188–206CrossRefPubMedGoogle Scholar
  4. 4.
    Atherton JC, Peek RM Jr, Tham KT, Cover TL, Blaser MJ (1997) Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori. Gastroenterology 112:92–99CrossRefPubMedGoogle Scholar
  5. 5.
    Basso D, Zambon CF, Letley DP, Stranges A, Marchet A, Rhead JL, Schiavon S, Guariso G, Ceroti M, Nitti D, Rugge M, Plebani M, Atherton JC (2008) Clinical relevance of Helicobacter pylori cagA and vacA gene polymorphisms. Gastroenterology 135:91–99CrossRefPubMedGoogle Scholar
  6. 6.
    Censini S, Lange C, Xiang Z, Crabtree JE, Ghiara P, Borodovsky M, Rappuoli R, Covacci A (1996) cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci USA 93:14648–14653CrossRefPubMedGoogle Scholar
  7. 7.
    Gerhard M, Lehn N, Neumayer N, Borén T, Rad R, Schepp W, Miehlke S, Classen M, Prinz C (1999) Clinical relevance of the Helicobacter pylori gene for blood-group antigen-binding adhesin. Proc Natl Acad Sci USA 96:12778–12783CrossRefPubMedGoogle Scholar
  8. 8.
    Lu H, Hsu PI, Graham DY, Yamaoka Y (2005) Duodenal ulcer promoting gene of Helicobacter pylori. Gastroenterology 128:833–848CrossRefPubMedGoogle Scholar
  9. 9.
    Yamaoka Y, Kikuchi S, el-Zimaity HM, Gutierrez O, Osato MS, Graham DY (2002) Importance of Helicobacter pylori oipA in clinical presentation, gastric inflammation, and mucosal interleukin 8 production. Gastroenterology 123:414–424CrossRefPubMedGoogle Scholar
  10. 10.
    Akopyants NS, Clifton SW, Kersulyte D, Crabtree JE, Youree BE, Reece CA, Bukanov NO, Drazek ES, Roe BA, Berg DE (1998) Analyses of the cag pathogenicity island of Helicobacter pylori. Mol Microbiol 28:37–53CrossRefPubMedGoogle Scholar
  11. 11.
    Backert S, Ziska E, Brinkmann V, Zimny-Arndt U, Fauconnier A, Jungblut PR, Naumann M, Meyer TF (2000) Translocation of the Helicobacter pylori CagA protein in gastric epithelial cells by a type IV secretion apparatus. Cell Microbiol 2:155–164CrossRefPubMedGoogle Scholar
  12. 12.
    Odenbreit S, Püls J, Sedlmaier B, Gerland E, Fischer W, Haas R (2000) Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science 287:1497–1500CrossRefPubMedGoogle Scholar
  13. 13.
    Viala J, Chaput C, Boneca IG, Cardona A, Girardin SE, Moran AP, Athman R, Mémet S, Huerre MR, Coyle AJ, DiStefano PS, Sansonetti PJ, Labigne A, Bertin J, Philpott DJ, Ferrero RL (2004) Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat Immunol 5:1166–1174CrossRefPubMedGoogle Scholar
  14. 14.
    Fischer W, Püls J, Buhrdorf R, Gebert B, Odenbreit S, Haas R (2001) Systematic mutagenesis of the Helicobacter pylori cag pathogenicity island: essential genes for CagA translocation in host cells and induction of interleukin-8. Mol Microbiol 42:1337–1348CrossRefPubMedGoogle Scholar
  15. 15.
    Selbach M, Moese S, Meyer TF, Backert S (2002) Functional analysis of the Helicobacter pylori cag pathogenicity island reveals both VirD4-CagA-dependent and VirD4-CagA-independent mechanisms. Infect Immun 70:665–671CrossRefPubMedGoogle Scholar
  16. 16.
    Kauser F, Khan AA, Hussain MA, Carroll IM, Ahmad N, Tiwari S, Shouche Y, Das B, Alam M, Ali SM, Habibullah CM, Sierra R, Mégraud F, Sechi LA, 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 42:5302–5308CrossRefPubMedGoogle Scholar
  17. 17.
    Cover TL, Blaser MJ (2009) Helicobacter pylori in health and disease. Gastroenterology 136:1863–1873CrossRefPubMedGoogle Scholar
  18. 18.
    Dixon MF, Genta RM, Yardley JH, Correa P (1996) Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol 20:1161–1181CrossRefPubMedGoogle Scholar
  19. 19.
    Uchida T, Kanada R, Tsukamoto Y, Hijiya N, Matsuura K, Yano S, Yokoyama S, Kishida T, Kodama M, Murakami K, Fujioka T, Moriyama M (2007) Immunohistochemical diagnosis of the cagA-gene genotype of Helicobacter pylori with anti-East Asian CagA-specific antibody. Cancer Sci 98:521–528CrossRefPubMedGoogle Scholar
  20. 20.
    Kudo T, Lu H, Wu JY, Ohno T, Wu MJ, Genta RM, Graham DY, Yamaoka Y (2007) Pattern of transcription factor activation in Helicobacter pylori-infected Mongolian gerbils. Gastroenterology 132:1024–1038CrossRefPubMedGoogle Scholar
  21. 21.
    Lu H, Wu JY, Kudo T, Ohno T, Graham DY, Yamaoka Y (2005) Regulation of interleukin-6 promoter activation in gastric epithelial cells infected with Helicobacter pylori. Mol Biol Cell 16:4954–4966CrossRefPubMedGoogle Scholar
  22. 22.
    Saito H, Yamaoka Y, Ishizone S, Maruta F, Sugiyama A, Graham DY, Yamauchi K, Ota H, Miyagawa S (2005) Roles of virD4 and cagG genes in the cag pathogenicity island of Helicobacter pylori using a Mongolian gerbil model. Gut 54:584–590CrossRefPubMedGoogle Scholar
  23. 23.
    Tabassam FH, Graham DY, Yamaoka Y (2008) OipA plays a role in Helicobacter pylori-induced focal adhesion kinase activation and cytoskeletal re-organization. Cell Microbiol 10:1008–1020CrossRefPubMedGoogle Scholar
  24. 24.
    Tabassam FH, Graham DY, Yamaoka Y (2009) Helicobacter pylori activate epidermal growth factor receptor- and phosphatidylinositol 3-OH kinase-dependent Akt and glycogen synthase kinase 3beta phosphorylation. Cell Microbiol 11:70–82CrossRefPubMedGoogle Scholar
  25. 25.
    Yamaoka Y, Kwon DH, Graham DY (2000) A M(r) 34,000 proinflammatory outer membrane protein (oipA) of Helicobacter pylori. Proc Natl Acad Sci USA 97:7533–7538CrossRefPubMedGoogle Scholar
  26. 26.
    Occhialini A, Marais A, Alm R, Garcia F, Sierra R, Mégraud F (2000) Distribution of open reading frames of plasticity region of strain J99 in Helicobacter pylori strains isolated from gastric carcinoma and gastritis patients in Costa Rica. Infect Immun 68:6240–6249CrossRefPubMedGoogle Scholar
  27. 27.
    Björkholm B, Lundin A, Sillén A, Guillemin K, Salama N, Rubio C, Gordon JI, Falk P, Engstrand L (2001) Comparison of genetic divergence and fitness between two subclones of Helicobacter pylori. Infect Immun 69:7832–7838CrossRefPubMedGoogle Scholar
  28. 28.
    Clyne M, Drumm B (1993) Adherence of Helicobacter pylori to primary human gastrointestinal cells. Infect Immun 61:4051–4057PubMedGoogle Scholar
  29. 29.
    Kwok T, Zabler D, Urman S, Rohde M, Hartig R, Wessler S, Misselwitz R, Berger J, Sewald N, König W, Backert S (2007) Helicobacter exploits integrin for type IV secretion and kinase activation. Nature 449:862–866CrossRefPubMedGoogle Scholar
  30. 30.
    Ikenoue T, Maeda S, Ogura K, Akanuma M, Mitsuno Y, Imai Y, Yoshida H, Shiratori Y, Omata M (2001) Determination of Helicobacter pylori virulence by simple gene analysis of the cag pathogenicity island. Clin Diagn Lab Immunol 8:181–186PubMedGoogle Scholar
  31. 31.
    Maeda S, Yoshida H, Ikenoue T, Ogura K, Kanai F, Kato N, Shiratori Y, Omata M (1999) Structure of cag pathogenicity island in Japanese Helicobacter pylori isolates. Gut 44:336–341PubMedCrossRefGoogle Scholar
  32. 32.
    Amieva MR, Vogelmann R, Covacci A, Tompkins LS, Nelson WJ, Falkow S (2003) Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA. Science 300:1430–1434CrossRefPubMedGoogle Scholar
  33. 33.
    Blaser MJ, Atherton JC (2004) Helicobacter pylori persistence: biology and disease. J Clin Invest 113:321–333PubMedGoogle Scholar
  34. 34.
    Mimuro H, Berg DE, Sasakawa C (2008) Control of epithelial cell structure and developmental fate: lessons from Helicobacter pylori. Bioessays 30:515–520CrossRefPubMedGoogle Scholar
  35. 35.
    Mimuro H, Suzuki T, Nagai S, Rieder G, Suzuki M, Nagai T, Fujita Y, Nagamatsu K, Ishijima N, Koyasu S, Haas R, Sasakawa C (2007) Helicobacter pylori dampens gut epithelial self-renewal by inhibiting apoptosis, a bacterial strategy to enhance colonization of the stomach. Cell Host Microbe 2:250–263CrossRefPubMedGoogle Scholar
  36. 36.
    Tan S, Tompkins LS, Amieva MR (2009) Helicobacter pylori usurps cell polarity to turn the cell surface into a replicative niche. PLoS Pathog 5(5):e1000407CrossRefPubMedGoogle Scholar
  37. 37.
    Dossumbekova A, Prinz C, Mages J, Lang R, Kusters JG, Van Vliet AH, Reindl W, Backert S, Saur D, Schmid RM, Rad R (2006) Helicobacter pylori HopH (OipA) and bacterial pathogenicity: genetic and functional genomic analysis of hopH gene polymorphisms. J Infect Dis 194:1346–1355CrossRefPubMedGoogle Scholar
  38. 38.
    Ilver D, Arnqvist A, Ogren J, Frick IM, Kersulyte D, Incecik ET, Berg DE, Covacci A, Engstrand L, Borén T (1998) Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging. Science 279:373–377CrossRefPubMedGoogle Scholar
  39. 39.
    Mahdavi J, Sondén B, Hurtig M, Olfat FO, Forsberg L, Roche N, Angstrom J, Larsson T, Teneberg S, Karlsson KA, Altraja S, Wadström T, Kersulyte D, Berg DE, Dubois A, Petersson C, Magnusson KE, Norberg T, Lindh F, Lundskog BB, Arnqvist A, Hammarström L, Borén T (2002) Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation. Science 297:573–578CrossRefPubMedGoogle Scholar
  40. 40.
    di Mario F, Cavallaro LG (2008) Non-invasive tests in gastric diseases. Dig Liver Dis 40:523–530CrossRefPubMedGoogle Scholar
  41. 41.
    Miki K, Urita Y (2007) Using serum pepsinogens wisely in a clinical practice. J Dig Dis 8:8–14CrossRefPubMedGoogle Scholar
  42. 42.
    Lorente S, Doiz O, Trinidad Serrano M, Castillo J, Lanas A (2002) Helicobacter pylori stimulates pepsinogen secretion from isolated human peptic cells. Gut 50:13–18CrossRefPubMedGoogle Scholar
  43. 43.
    Di Mario F, Cavallaro LG, Moussa AM, Caruana P, Merli R, Maini A, Bertolini S, Dal Bó N, Rugge M, Cavestro GM, Aragona G, Plebani M, Franzé A, Nervi G (2006) Usefulness of serum pepsinogens in Helicobacter pylori chronic gastritis: relationship with inflammation, activity, and density of the bacterium. Dig Dis Sci 51:1791–1795CrossRefPubMedGoogle Scholar
  44. 44.
    Wagner S, Haruma K, Gladziwa U, Soudah B, Gebel M, Bleck J, Schmidt H, Manns M (1994) Helicobacter pylori infection and serum pepsinogen A, pepsinogen C, and gastrin in gastritis and peptic ulcer: significance of inflammation and effect of bacterial eradication. Am J Gastroenterol 89:1211–1218PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • L. T. Nguyen
    • 1
    • 2
  • T. Uchida
    • 1
    • 3
  • Y. Tsukamoto
    • 1
  • T. D. Trinh
    • 4
  • L. Ta
    • 4
  • H. B. Mai
    • 4
  • H. S. Le
    • 4
  • D. Q. D. Ho
    • 5
  • H. H. Hoang
    • 5
  • T. Matsuhisa
    • 6
  • T. Okimoto
    • 2
  • M. Kodama
    • 2
  • K. Murakami
    • 2
  • T. Fujioka
    • 2
  • Y. Yamaoka
    • 7
  • M. Moriyama
    • 1
  1. 1.Department of Molecular Pathology, Faculty of MedicineOita UniversityYufu City, OitaJapan
  2. 2.Department of Gastroenterology, Faculty of MedicineOita UniversityOitaJapan
  3. 3.Department of Human Environmental and Social Medicine, Faculty of MedicineOita UniversityOitaJapan
  4. 4.108 HospitalHanoiVietnam
  5. 5.Cho Ray HospitalHo Chi MinhVietnam
  6. 6.Department of Gastrointestinal Endoscopy, Tama-Nagayama HospitalNippon Medical SchoolTokyoJapan
  7. 7.Department of Environmental and Preventive Medicine, Faculty of MedicineOita UniversityOitaJapan

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