Skip to main content

Advertisement

SpringerLink
Log in

Helicobacter pylori with the Intact dupA Cluster is more Virulent than the Strains with the Incomplete dupA Cluster

  • Published:
Current Microbiology Aims and scope Submit manuscript

Abstract

The duodenal ulcer promoting gene (dupA), located in the plasticity region of Helicobacter pylori (H. pylori), is predicted to form a type IV secretory system (T4SS) with vir genes around dupA. In the study, we investigated the association between the dupA cluster status and the virulence of H. pylori in a littoral region of Northeast China. Two hundred and sixty-two H. pylori strains isolated from the chronic gastritis were examined to evaluate the dupA cluster status, cag PAI genes and vacA genotype using PCR and Western blot. Histopathologic evaluations of biopsy specimens were performed to analysis the association between the dupA cluster and the inflammatory response. IL-8 productions in gastric mucosa and from GES-1 cells co-cultured with H. pylori were measured, respectively, to analysis the association between the dupA cluster status and IL-8 production. We found that gastric mucosal inflammatory cell infiltration was significantly higher in patients with dupA-positive H. pylori, including H. pylori with complete dupA cluster (2.71 ± 0.79) and incomplete dupA cluster (2.09 ± 0.61) than in patients with dupA-negative strain (1.73 ± 0.60, p < 0.01), whereas no significant difference in the gastric mucosal atrophy was found according to the status of dupA cluster. Gastric mucosal IL-8 levels were higher in the complete dupA cluster group than in other groups (p < 0.01), and IL-8 production from GES-1 cells was also significantly higher in strains with a complete dupA cluster (1527.9 ± 180.0 pg/ml) than in those with an incomplete dupA cluster (1229.4 ± 75.3 pg/ml, p < 0.01) or those with dupA negative (1201.9 ± 92.3 pg/ml, p < 0.01). In conclusion, the complete dupA cluster in H. pylori is associated with inflammatory cell infiltration and IL-8 secretion, and H. pylori strain with a complete dupA cluster seems to be more virulent than other strains with the incomplete dupA cluster or dupA negative.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. El-Zimaity HM, Graham DY, Al-Assi MT, Malaty H, Karttunen TJ, Graham DP, Huberman RM, Genta RM (1996) Interobserver variation in the histopathological assessment of Helicobacter pylori gastritis. Hum Pathol 27:35–41

    Article  CAS  PubMed  Google Scholar 

  2. Falush D, Wirth T, Linz B, Pritchard JK, Stephens M, Kidd M, Blaser MJ, Graham DY, Vacher S, Perez-Perez GI, Yamaoka Y, Mégraud F, Otto K, Reichard U, Katzowitsch E, Wang X, Achtman M, Suerbaum S (2003) Traces of human migrations in Helicobacter pylori populations. Science 299(5612):1582–1585

    Article  CAS  PubMed  Google Scholar 

  3. Fischer W, Windhager L, Rohrer S, Zeiller M, Karnholz A, Hoffmann R, Zimmer R, Haas R (2010) Strain-specific genes of Helicobacter pylori: genome evolution driven by a novel type IV secretion system and genomic island transfer. Nucleic Acids Res 38(18):6089–6101

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Gomes LI, Rocha GA, Rocha AM, Soares TF, Oliveira CA, Bittencourt PF, Queiroz DM (2008) Lack of association between Helicobacter pylori infection with dupA-positive strains and gastroduodenal diseases in Brazilian patients. Int J Med Microbiol 298(3–4):223–230

    Article  CAS  PubMed  Google Scholar 

  5. Hussein NR, Argent RH, Marx CK, Patel SR, Robinson K, Atherton JC (2010) Helicobacter pylori dupA is polymorphic, and its active form induces proinflammatory cytokine secretion by mononuclear cells. J Infect Dis 202(2):261–269

    Article  CAS  PubMed  Google Scholar 

  6. Hussein NR (2010) The association of dupA and Helicobacter pylori-related gastroduodenal diseases. Eur J Clin Microbiol Infect Dis 29(7):817–821

    Article  CAS  PubMed  Google Scholar 

  7. Hussein NR, Argent RH, Marx CK, Patel SR, Robinson K, Atherton JC (2010) Helicobacter pylori dupA is polymorphic, and its active form induces proinflammatory cytokine secretion by mononuclear cells. J Infect Dis 202(2):261–269

    Article  CAS  PubMed  Google Scholar 

  8. Jung SW, Sugimoto M, Shiota S, Graham DY, Yamaoka Y (2012) The intact dupA cluster is a more reliable Helicobacter pylori virulence marker than dupA alone. Infect Immun 80(1):381–387

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Kersulyte D, Lee W, Subramaniam D, Anant S, Herrera P, Cabrera L, Balqui J, Barabas O, Kalia A, Gilman RH, Berg DE (2009) Helicobacter Pylori’s plasticity zones are novel transposable elements. PLoS One 4(9):e6859

    Article  PubMed Central  PubMed  Google Scholar 

  10. Kauser F, Hussain MA, Ahmed I, Ahmad N, Habeeb A, Khan AA, Ahmed N (2005) Comparing genomes of Helicobacter pylori strains from the high-altitude desert of Ladakh, India. J Clin Microbiol 43(4):1538–1545

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Lu H, Yamaoka Y, Graham DY (2005) Helicobacter pylori virulence factors: facts and fantasies. Curr Opin Gastroenterol 21(6):653–659

    Article  PubMed  Google Scholar 

  12. Nguyen LT, Uchida T, Tsukamoto Y, Kuroda A, Okimoto T, Kodama M, Murakami K, Fujioka T, Moriyama M (2010) Helicobacter pylori dupA gene is not associated with clinical outcomes in the Japanese population. Clin Microbiol Infect 16(8):1264–1269

    Article  CAS  PubMed  Google Scholar 

  13. Queiroz DM, Moura SB, Rocha AM, Costa RF, Anacleto C, Rocha GA (2011) The genotype of the Brazilian dupA-positive Helicobacter pylori strains is dupA1. J Infect Dis 203(7):1033–1034

    Article  PubMed  Google Scholar 

  14. Schmidt HM, Andres S, Nilsson C, Kovach Z, Kaakoush NO, Engstrand L, Goh KL, Fock KM, Forman D, Mitchell H (2010) The cagPAI is intact and functional but HP0521 varies significantly in Helicobacter pylori isolates from Malaysia and Singapore. Eur J Clin Microbiol Infect Dis 29(4):439–451

    Article  CAS  PubMed  Google Scholar 

  15. Takahashi A, Shiota S, Matsunari O, Watada M, Suzuki R, Nakachi S, Kinjo N, Kinjo F, Yamaoka Y (2013) Intact long-type dupA as a marker for gastroduodenal diseases in Okinawan subpopulation, Japan. Helicobacter 18(1):66–72

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Tan HJ, Rizal AM, Rosmadi MY, Goh KL (2005) Distribution of Helicobacter pylori cagA, cagE and vacA in different ethnic groups in Kuala Lumpur, Malaysia. J Gastroenterol Hepatol 20(4):589–594

    Article  CAS  PubMed  Google Scholar 

  17. Wang MY, Chen C, Gao XZ, Li J, Yue J, Ling F, Wang XC, Shao SH (2013) Distribution of Helicobacter pylori virulence markers in patients with gastroduodenal diseases in a region at high risk of gastric cancer. Microb Pathog 59–60:13–18

    Article  PubMed  Google Scholar 

  18. Wang MY, Lin J, Sun SB, Yuan XY (2012) Identification of Granulicatella elegans from a case of infective endocarditis, based on the phenotypic characteristics and 16SrRNA gene sequence. J Cardiovasc Med (Hagerstown) 16(Suppl 2):S138–S140

    Google Scholar 

  19. Yamaoka Y (2008) Roles of the plasticity regions of Helicobacter pylori in gastroduodenal pathogenesis. J Med Microbiol 57(Pt 5):545–553

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Yakoob J, Abid S, Abbas Z, Jafri W, Ahmad Z, Ahmed R, Islam M (2009) Distribution of Helicobacter pylori virulence markers in patients with gastroduodenal diseases in Pakistan. BMC Gastroenterol 9:87

    Article  PubMed Central  PubMed  Google Scholar 

  21. Yamaoka Y (2010) Mechanisms of disease: Helicobacter pylori virulence factors. Nat Rev Gastroenterol Hepatol 7(11):629–641

    CAS  PubMed Central  PubMed  Google Scholar 

  22. Yamaoka Y (2012) Pathogenesis of Helicobacter pylori-related gastroduodenal diseases from molecular epidemiological studies. Gastroenterol Res Pract 2012:371503

    Article  PubMed Central  PubMed  Google Scholar 

  23. 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(Pt 3):231–235

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the 2012 Program Sponsored for Scientific Innovation Research of College Graduate in Jiangsu Province (No. CXLX12_0674), the National Natural Science Foundation of China (Grant No. 81271795) and the 2013 Technology Development Project of Shandong Medicine and Health Science (No. 2013WS0065).

Author information

Authors and Affiliations

  1. School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, People’s Republic of China

    Ming-yi Wang, Chen Shao & Shi-he Shao

  2. Department of Clinical Lab, Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai, Shandong, 264200, People’s Republic of China

    Ming-yi Wang, Jie Li, Ya-Chao Yang, Shao-bo Wang, Jun-ling Hao & Chun-mei Wu

  3. Department of Gastroenterology, Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai, Shandong, 264200, People’s Republic of China

    Xiao-zhong Gao

Authors
  1. Ming-yi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chen Shao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jie Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ya-Chao Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shao-bo Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jun-ling Hao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chun-mei Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiao-zhong Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shi-he Shao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shi-he Shao.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, My., Shao, C., Li, J. et al. Helicobacter pylori with the Intact dupA Cluster is more Virulent than the Strains with the Incomplete dupA Cluster. Curr Microbiol 71, 16–23 (2015). https://doi.org/10.1007/s00284-015-0812-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00284-015-0812-z

Keywords

Search

Navigation