Digestive Diseases and Sciences

, Volume 61, Issue 10, pp 2868–2877 | Cite as

Helicobacter pylori Strains from Duodenal Ulcer Patients Exhibit Mixed babA/B Genotypes with Low Levels of BabA Adhesin and Lewis b Binding

  • Samaneh Saberi
  • Alexej Schmidt
  • Sana Eybpoosh
  • Maryam Esmaili
  • Yeganeh Talebkhan
  • Nazanin Mohajerani
  • Akbar Oghalaie
  • Mahmoud Eshagh Hosseini
  • Mohammad Ali Mohagheghi
  • Jeanna Bugaytova
  • Thomas Borén
  • Marjan Mohammadi
Original Article



BabA is a Helicobacter pylori cell surface adhesin, which binds to the ABO/Leb histo-blood group antigens (Leb) and serves as a virulence factor.


H. pylori single colonies were isolated from 156 [non-ulcer dyspepsia (NUD) = 97, duodenal ulcer (DU) = 34, gastric cancer (GC) = 25)] patients. babA and babB genes were evaluated by gene/locus-specific PCR. BabA protein expression and Leb binding activity were determined by immunoblotting and ELISA, respectively.


The combined categorization of H. pylori strains based on high, low or no levels of BabA expression and Leb binding, produced 4 groups: (I) BabA-high/Leb-high (36 %), (II) BabA-low/Leb-low (26 %), (III) BabA-neg/Leb-low (30 %) and (IV) BabA-neg/Leb-neg (8 %) strains. The majority (63 %) of the BabA-low/Leb-low strains exhibited mixed babA/B genotypes as compared to merely 18 % of the BabA-high/Leb-high, 15 % of the BabA-neg/Leb-neg and 11 % of the BabA-neg/Leb-low (P = 0.0001) strains. In contrast to NUD strains, the great majority (70 %) of DU strains were BabA-low/Leb-low (11 %, P = 0.0001), which compared to NUD strains, enhanced the risk of DU by 18.8-fold. In parallel, infection with babA/B mixed genotype strains amplified the risk of DU by 3.6-fold (vs. babA-positive: P = 0.01) to 6.9-fold (vs. babA-negative: P = 0.007).


Here, we show higher prevalence of mixed babA/B genotypes among BabA-low/Leb-low clinical strains. Recombination of babA and babB genes across their loci may yield lower BabA expression and lower Leb binding activity. We conclude that H. pylori strains with lower Leb binding activity are better adapted for colonization of the gastric metaplastic patches in the duodenum and enhance the risk of duodenal ulcers.


Helicobacter pylori Duodenal ulcer Mixed babA/B genotypes BabA Adhesin 



This study was generously supported by a technical assistance grant (IRN-072) to M.M., which was co-funded by the Islamic Development Bank, Saudi Arabia, and Pasteur Institute of Iran. T.B. is the founder of Helicure and a member of its scientific advisory board. He is supported by grants from Vetenskapsrådet/VR, Cancerfonden, the J.C. Kempe and Seth M. Kempe Memorial Foundation and the Knut and Alice Wallenberg Foundation (2012.0090).

Compliance with ethical standards

Conflicts of interest

The authors disclose no conflicts of interest.

Supplementary material

10620_2016_4217_MOESM1_ESM.docx (184 kb)
Supplementary material 1 (DOCX 185 kb)


  1. 1.
    Araujo MB, Borini P, Guimaraes RC. Etiopathogenesis of peptic ulcer: back to the past? Arq Gastroenterol. 2014;51:155–161.CrossRefPubMedGoogle Scholar
  2. 2.
    Correa P. Gastric cancer: overview. Gastroenterol Clin N Am. 2013;42:211–217.CrossRefGoogle Scholar
  3. 3.
    Ahmed N, Loke MF, Kumar N, Vadivelu J. Helicobacter pylori in 2013: multiplying genomes, emerging insights. Helicobacter. 2013;18:1–4.CrossRefPubMedGoogle Scholar
  4. 4.
    Amieva MR, El-Omar EM. Host-bacterial interactions in Helicobacter pylori infection. Gastroenterology. 2008;134:306–323.CrossRefPubMedGoogle Scholar
  5. 5.
    Posselt G, Backert S, Wessler S. The functional interplay of Helicobacter pylori factors with gastric epithelial cells induces a multi-step process in pathogenesis. Cell Commun Signal. 2013;11:77.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Ilver D, Arnqvist A, Ogren J et al. Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging. Science (New York, N.Y.). 1998;279:373–377.Google Scholar
  7. 7.
    Mahdavi J, Sonden B, Hurtig M et al. Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation. Science (New York, N.Y.). 2002;297:573–578.Google Scholar
  8. 8.
    Rossez Y, Gosset P, Boneca IG, et al. The lacdiNAc-specific adhesin LabA mediates adhesion of Helicobacter pylori to human gastric mucosa. J Infect Dis. 2014;210:1286–1295.CrossRefPubMedGoogle Scholar
  9. 9.
    Boren T, Falk P, Roth KA, Larson G, Normark S. Attachment of Helicobacter pylori to human gastric epithelium mediated by blood group antigens. Science (New York, N.Y.). 1993;262:1892–1895.Google Scholar
  10. 10.
    Aspholm-Hurtig M, Dailide G, Lahmann M et al. Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin. Science (New York, N.Y.). 2004;305:519–522.Google Scholar
  11. 11.
    Linden S, Nordman H, Hedenbro J, Hurtig M, Boren T, Carlstedt I. Strain- and blood group-dependent binding of Helicobacter pylori to human gastric MUC5AC glycoforms. Gastroenterology. 2002;123:1923–1930.CrossRefPubMedGoogle Scholar
  12. 12.
    Walz A, Odenbreit S, Stuhler K, et al. Identification of glycoprotein receptors within the human salivary proteome for the lectin-like BabA and SabA adhesins of Helicobacter pylori by fluorescence-based 2-D bacterial overlay. Proteomics. 2009;9:1582–1592.CrossRefPubMedGoogle Scholar
  13. 13.
    Alm RA, Bina J, Andrews BM, Doig P, Hancock RE, Trust TJ. Comparative genomics of Helicobacter pylori: analysis of the outer membrane protein families. Infect Immun. 2000;68:4155–4168.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Moonens K, Gideonsson P, Subedi S, et al. Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori. Cell Host Microbe. 2016;19:55–66.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Hage N, Howard T, Phillips C, et al. Structural basis of Lewis(b) antigen binding by the Helicobacter pylori adhesin BabA. Sci. Adv.. 2015;1:e1500315.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Gerhard M, Lehn N, Neumayer N, et al. Clinical relevance of the Helicobacter pylori gene for blood-group antigen-binding adhesin. Proc Natl Acad Sci USA. 1999;96:12778–12783.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Moore ME, Boren T, Solnick JV. Life at the margins: modulation of attachment proteins in Helicobacter pylori. Gut Microbes. 2011;2:42–46.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Yamaoka Y. Roles of Helicobacter pylori BabA in gastroduodenal pathogenesis. World J Gastroenterol. 2008;14:4265–4272.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Colbeck JC, Hansen LM, Fong JM, Solnick JV. Genotypic profile of the outer membrane proteins BabA and BabB in clinical isolates of Helicobacter pylori. Infect Immun. 2006;74:4375–4378.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Hennig EE, Allen JM, Cover TL. Multiple chromosomal loci for the babA gene in Helicobacter pylori. Infect Immun. 2006;74:3046–3051.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Backstrom A, Lundberg C, Kersulyte D, Berg DE, Boren T, Arnqvist A. Metastability of Helicobacter pylori bab adhesin genes and dynamics in Lewis b antigen binding. Proc Natl Acad Sci USA. 2004;101:16923–16928.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Solnick JV, Hansen LM, Salama NR, Boonjakuakul JK, Syvanen M. Modification of Helicobacter pylori outer membrane protein expression during experimental infection of rhesus macaques. Proc Natl Acad Sci USA. 2004;101:2106–2111.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Styer CM, Hansen LM, Cooke CL, et al. Expression of the BabA adhesin during experimental infection with Helicobacter pylori. Infect Immun. 2010;78:1593–1600.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Pride DT, Blaser MJ. Concerted evolution between duplicated genetic elements in Helicobacter pylori. J Mol Biol. 2002;316:629–642.CrossRefPubMedGoogle Scholar
  25. 25.
    Suerbaum S, Josenhans C. Helicobacter pylori evolution and phenotypic diversification in a changing host. Nature Rev Microbiol. 2007;5:441–452.CrossRefGoogle Scholar
  26. 26.
    Oliveira AG, Santos A, Guerra JBet al.. babA2- and cagA-positive Helicobacter pylori strains are associated with duodenal ulcer and gastric carcinoma in Brazil. J Clin Microbiol. 2003;41:3964–3966.Google Scholar
  27. 27.
    Gatti LL, Modena JL, Payao SL, et al. Prevalence of Helicobacter pylori cagA, iceA and babA2 alleles in Brazilian patients with upper gastrointestinal diseases. Acta Trop. 2006;100:232–240.CrossRefPubMedGoogle Scholar
  28. 28.
    Chen MY, He CY, Meng X, Yuan Y. Association of Helicobacter pylori babA2 with peptic ulcer disease and gastric cancer. World J Gastroenterol. 2013;19:4242–4251.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Fujimoto S, Olaniyi OO, Arnqvist A, et al. Helicobacter pylori BabA expression, gastric mucosal injury, and clinical outcome. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc.. 2007;5:49–58.Google Scholar
  30. 30.
    Odenbreit S, Kavermann H, Puls J, Haas R. CagA tyrosine phosphorylation and interleukin-8 induction by Helicobacter pylori are independent from alpAB, HopZ and bab group outer membrane proteins. Int J Med Microbiol. 2002;292:257–266.CrossRefPubMedGoogle Scholar
  31. 31.
    Labigne A, Cussac V, Courcoux P. Shuttle cloning and nucleotide sequences of Helicobacter pylori genes responsible for urease activity. J Bacteriol. 1991;173:1920–1931.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Tummuru MK, Cover TL, Blaser MJ. Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production. Infect Immun. 1993;61:1799–1809.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Atherton JC, Cao P, Peek RM Jr, Tummuru MK, Blaser MJ, Cover TL. Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem. 1995;270:17771–17777.CrossRefPubMedGoogle Scholar
  34. 34.
    Shiotani A, Graham DY. Pathogenesis and therapy of gastric and duodenal ulcer disease. Med Clin N Am. 2002;86:1447–1466, viii.Google Scholar
  35. 35.
    Matteo MJ, Armitano RI, Romeo M, Wonaga A, Olmos M, Catalano M. Helicobacter pylori bab genes during chronic colonization. Int J Mol Epidemiol Genetics. 2011;2:286–291.Google Scholar
  36. 36.
    Sheu SM, Sheu BS, Chiang WC, et al. H. pylori clinical isolates have diverse babAB genotype distributions over different topographic sites of stomach with correlation to clinical disease outcomes. BMC Microbiol. 2012;12:89.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Nell S, Kennemann L, Schwarz S, Josenhans C, Suerbaum S. Dynamics of Lewis b binding and sequence variation of the babA adhesin gene during chronic Helicobacter pylori infection in humans. mBio. 2014;5:e02281–14.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Kivi M, Tindberg Y, Sorberg M, et al. Concordance of Helicobacter pylori strains within families. J Clin Microbiol. 2003;41:5604–5608.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Whitney AE, Guarner J, Hutwagner L, Gold BD. Helicobacter pylori gastritis in children and adults: comparative histopathologic study. Ann Diagn Pathol.. 2000;4:279–285.CrossRefPubMedGoogle Scholar
  40. 40.
    Bry L, Falk PG, Midtvedt T, Gordon JI. A model of host-microbial interactions in an open mammalian ecosystem. Science (New York, N.Y.). 1996;273:1380–1383.Google Scholar
  41. 41.
    Olfat FO, Zheng Q, Oleastro M, et al. Correlation of the Helicobacter pylori adherence factor BabA with duodenal ulcer disease in four European countries. FEMS Immunol Med Microbiol. 2005;44:151–156.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Samaneh Saberi
    • 1
  • Alexej Schmidt
    • 2
  • Sana Eybpoosh
    • 3
  • Maryam Esmaili
    • 1
  • Yeganeh Talebkhan
    • 1
  • Nazanin Mohajerani
    • 1
  • Akbar Oghalaie
    • 1
  • Mahmoud Eshagh Hosseini
    • 4
  • Mohammad Ali Mohagheghi
    • 5
  • Jeanna Bugaytova
    • 6
  • Thomas Borén
    • 6
  • Marjan Mohammadi
    • 1
  1. 1.HPGC Group, Department of Medical Biotechnology, Biotechnology Research CenterPasteur Institute of IranTehranIran
  2. 2.Department of Medical Biosciences and PathologyUmeå UniversityUmeåSweden
  3. 3.Research Center for Modeling in Health, Institute for Future Studies in HealthKerman University of Medical SciencesKermanIran
  4. 4.Department of Gastroenterology, Amiralam HospitalTehran University of Medical SciencesTehranIran
  5. 5.Cancer Research CenterTehran University of Medical SciencesTehranIran
  6. 6.Department of Medical Biochemistry and BiophysicsUmeå UniversityUmeåSweden

Personalised recommendations