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

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Abstract

Background

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.

Methods

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.

Results

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).

Conclusions

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.

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Acknowledgments

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).

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Authors and Affiliations

  1. HPGC Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, 1316943551, Iran

    Samaneh Saberi, Maryam Esmaili, Yeganeh Talebkhan, Nazanin Mohajerani, Akbar Oghalaie & Marjan Mohammadi

  2. Department of Medical Biosciences and Pathology, Umeå University, 901 85, Umeå, Sweden

    Alexej Schmidt

  3. Research Center for Modeling in Health, Institute for Future Studies in Health, Kerman University of Medical Sciences, Kerman, 7618747653, Iran

    Sana Eybpoosh

  4. Department of Gastroenterology, Amiralam Hospital, Tehran University of Medical Sciences, Tehran, 1145765111, Iran

    Mahmoud Eshagh Hosseini

  5. Cancer Research Center, Tehran University of Medical Sciences, Tehran, 141979733141, Iran

    Mohammad Ali Mohagheghi

  6. Department of Medical Biochemistry and Biophysics, Umeå University, 901 87, Umeå, Sweden

    Jeanna Bugaytova & Thomas Borén

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  1. Samaneh Saberi
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Correspondence to Thomas Borén or Marjan Mohammadi.

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Majran Mohammadi is the first corresponding author.

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Saberi, S., Schmidt, A., Eybpoosh, S. et al. Helicobacter pylori Strains from Duodenal Ulcer Patients Exhibit Mixed babA/B Genotypes with Low Levels of BabA Adhesin and Lewis b Binding. Dig Dis Sci 61, 2868–2877 (2016). https://doi.org/10.1007/s10620-016-4217-z

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