A single-nucleotide polymorphism in Helicobacter pylori promotes gastric cancer development

Sharafutdinov I, Tegtmeyer-Backert N, Linz B, Rohde M, Vieth M, Tay ACY, Lamichhane B, Tuan VP, Fauzia KA, Sticht H, Yamaoka Y, Marshall BJ, Backert S (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Cell Host & Microbe Elsevier (Cell Press)

Book Volume: 31

Pages Range: 1345-1358.e6

Journal Issue: 8

DOI: 10.1016/j.chom.2023.06.016

Abstract

Single-nucleotide polymorphisms (SNPs) in various human genes are key factors in carcinogenesis. However, whether SNPs in bacterial pathogens are similarly crucial in cancer development is unknown. Here, we analyzed 1,043 genomes of the stomach pathogen Helicobacter pylori and pinpointed a SNP in the serine protease HtrA (position serine/leucine 171) that significantly correlates with gastric cancer. Our functional studies reveal that the 171S-to-171L mutation triggers HtrA trimer formation and enhances proteolytic activity and cleavage of epithelial junction proteins occludin and tumor-suppressor E-cadherin. 171L-type HtrA, but not 171S-HtrA-possessing H. pylori, inflicts severe epithelial damage, enhances injection of oncoprotein CagA into epithelial cells, increases NF-κB-mediated inflammation and cell proliferation through nuclear accumulation of β-catenin, and promotes host DNA double-strand breaks, collectively triggering malignant changes. These findings highlight the 171S/L HtrA mutation as a unique bacterial cancer-associated SNP and as a potential biomarker for risk predictions in H. pylori infections.

Authors with CRIS profile

Irshad Sharafutdinov Lehrstuhl für Mikrobiologie Nicole Tegtmeyer-Backert Lehrstuhl für Mikrobiologie Bodo Linz Lehrstuhl für Mikrobiologie Michael Vieth Professur für Allgemeine Pathologie Heinrich Sticht Professur für Bioinformatik Steffen Backert Lehrstuhl für Mikrobiologie

Involved external institutions

University of Western Australia (UWA) AU Australia (AU) Chợ Rẫy Hospital VN Viet Nam (VN) Oita University / 大分大学 JP Japan (JP) Helmholtz-Zentrum für Infektionsforschung (HZI) DE Germany (DE)

How to cite

APA:

Sharafutdinov, I., Tegtmeyer-Backert, N., Linz, B., Rohde, M., Vieth, M., Tay, A.C.Y.,... Backert, S. (2023). A single-nucleotide polymorphism in Helicobacter pylori promotes gastric cancer development. Cell Host & Microbe, 31(8), 1345-1358.e6. https://dx.doi.org/10.1016/j.chom.2023.06.016

MLA:

Sharafutdinov, Irshad, et al. "A single-nucleotide polymorphism in Helicobacter pylori promotes gastric cancer development." Cell Host & Microbe 31.8 (2023): 1345-1358.e6.

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