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Transcriptional analysis of Helicobacter pylori cytotoxic-associated gene-pathogenicity island in response to different pH levels and proton pump inhibitor exposure

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Abstract

Background

Long-term use of proton pump inhibitors (PPIs) can increase the risk of gastric cancer in Helicobacter pylori–infected patients; nevertheless, there is no data about their impact on the pathogenicity of H. pylori. This study aimed at investigating the transcriptional alteration of key gene mediators of cytotoxin-associated gene-pathogenicity island (cag-PAI) among clinical H. pylori isolates in response to omeprazole at different pH levels.

Methods

Accordingly, H. pylori isolates with the same virulence genotypes selected from the gastric biopsies of patients and transcriptional alteration in the cag-PAI genes studied in the presence or absence of omeprazole (2 mg/mL) at pH 2.0, 4.0 and 7.0 after 30 and 90 minutes of the treatment. Relative changes in the transcriptional levels were recorded in each assay, separately.

Results

Of 18 H. pylori isolates, the cag-PAI empty site was detected in four strains, while the presence of cagA, cagL and cagY was characterized in 77.7%, 83.3% and 83.3% of the cag-PAI-positive strains, respectively. Transcriptional analysis of the selected strains showed up-regulation of cagA and cagL, mainly at pH 2.0 and 4.0 after 30 and 90-minute exposure. A diversity in the expression levels of cag-PAI genes was seen among the strains at the extent and time of induction.

Conclusion

Our results showed that omeprazole could increase the expression of H. pylori cagA and cagL at acidic pH. Heterogeneity among the strains probably has an impact on the extent of their interplay with PPIs. Further studies are needed to establish this correlation.

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Data availability

The data that support the findings of this study are available on request from the corresponding authors (M.A. and R.B.).

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Acknowledgements

The authors would like to thank Prof. Hashem Fakhre Yaseri in Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran, and Gastroenterology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran, for his cooperation in this study and also thank the kind support of gastroenterology and pathology units of Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran.

Funding

This study was funded by a master degree grant (Code: 98–02-27–43053) from the Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

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Authors and Affiliations

  1. Department of Pathobiology, School of Public Health and Institute Health Research, Tehran University of Medical Sciences, Tehran, Iran

    Fatemeh Rezaei, Seyedeh Zohre Mirbagheri, Amir Ebrahimi & Ronak Bakhtiari

  2. Pediatric Infections Research Centre, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Masoud Alebouyeh

  3. Department of Epidemiology and Biostatistics, School of Public Health and Institute Health Research, Tehran University of Medical Sciences, Tehran, Iran

    Abbas Rahimi Foroushani

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Contributions

Conceptualization and design: RB and MA; methodology: FR, RB, SZM, AE, ARF and MA; formal analysis: FR, RB, SZM, AE, ARF and MA; writing—original draft: FR, RB, SZM and MA; writing—review and editing: FR, SZM and MA; approval of final manuscript: all authors.

Corresponding author

Correspondence to Ronak Bakhtiari.

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Conflict of interest

FR, MA, SZM, AE, ARF and RB declare that they have no conflict of interest.

Ethics approval and consent to participate

The study was performed on human samples and the authors followed the policy concerning informed consent and informed consent was obtained from all individual participants included in the study. This study was approved by the ethical committee of the Research Center in Tehran University of Medical Science (accepted number, IR.TUMS.SPH.REC.98–02-27–43053).

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Fatemeh Rezaei and Masoud Alebouyeh contributed equally to this study and designated as co-first authors.

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Rezaei, F., Alebouyeh, M., Mirbagheri, S.Z. et al. Transcriptional analysis of Helicobacter pylori cytotoxic-associated gene-pathogenicity island in response to different pH levels and proton pump inhibitor exposure. Indian J Gastroenterol 42, 686–693 (2023). https://doi.org/10.1007/s12664-023-01422-z

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