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Biochim Biophys Acta. 2015 Sep;1852(9):1928-39. doi: 10.1016/j.bbadis.2015.07.001. Epub 2015 Jul 2.

Helicobacter pylori chronic infection and mucosal inflammation switches the human gastric glycosylation pathways.

Author information

1
Institute for Research and Innovation in Health (i3S), University of Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal.
2
Centro Hospitalar do Porto (CHP), Gastroenterology Department, Portugal; Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Portugal; Medical Faculty, University of Porto, Portugal.
3
Complex Carbohydrate Research Center and Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA.
4
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal.
5
Institute for Research and Innovation in Health (i3S), University of Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal; Section of Health Sciences, University of Aveiro, Portugal.
6
Department of Pathology, Centro Hospitalar São João, Porto, Portugal; Centro Hospitalar Vila Nova de Gaia/Espinho, Portugal.
7
Institute for Research and Innovation in Health (i3S), University of Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal; Medical Faculty, University of Porto, Portugal.
8
Medical Faculty, University of Porto, Portugal; Gastroenterology Department, IPO Porto, Portugal; CIDES/CINTESIS, University of Porto, Portugal.
9
Institute for Research and Innovation in Health (i3S), University of Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal; Medical Faculty, University of Porto, Portugal; Department of Pathology, Centro Hospitalar São João, Porto, Portugal.
10
Institute for Research and Innovation in Health (i3S), University of Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal; Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Portugal; Medical Faculty, University of Porto, Portugal. Electronic address: celsor@ipatimup.pt.

Abstract

Helicobacter pylori exploits host glycoconjugates to colonize the gastric niche. Infection can persist for decades promoting chronic inflammation, and in a subset of individuals lesions can silently progress to cancer. This study shows that H. pylori chronic infection and gastric tissue inflammation result in a remodeling of the gastric glycophenotype with increased expression of sialyl-Lewis a/x antigens due to transcriptional up-regulation of the B3GNT5, B3GALT5, and FUT3 genes. We observed that H. pylori infected individuals present a marked gastric local pro-inflammatory signature with significantly higher TNF-α levels and demonstrated that TNF-induced activation of the NF-kappaB pathway results in B3GNT5 transcriptional up-regulation. Furthermore, we show that this gastric glycosylation shift, characterized by increased sialylation patterns, favors SabA-mediated H. pylori attachment to human inflamed gastric mucosa. This study provides novel clinically relevant insights into the regulatory mechanisms underlying H. pylori modulation of host glycosylation machinery, and phenotypic alterations crucial for life-long infection. Moreover, the biosynthetic pathways here identified as responsible for gastric mucosa increased sialylation, in response to H. pylori infection, can be exploited as drug targets for hindering bacteria adhesion and counteract the infection chronicity.

KEYWORDS:

Chronic infection; Glycophenotype; Helicobacter pylori; Sialic acid-binding adhesin

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