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Author(s): Magalhães, A
Marcos-Pinto, R
Nairn, A
dela Rosa, M
Ferreira, RM
Junqueira-Neto, S
Freitas, DP
Gomes J
Oliveira, P
Santos, M
Marcos, N
Xiaogang, W
Figueiredo, C
Oliveira, C
Dinis-Ribeiro, M
Carneiro, F
Moremen, K
David, L
Reis, CA
Title: Helicobacter pylori chronic infection and mucosal inflammation switches the human gastric glycosylation pathways
Publisher: Elsevier
Issue Date: 2015
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-a 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.
Subject: Chronic infection
Helicobacter pylori
Sialic acid-binding adhesin
Source: Biochimica et Biophysica Acta - Molecular Basis of Disease, vol.1852(9), p. 1928-1939
Related Information: info:eu-repo/grantAgreement/FCT/COMPETE/132983/PT
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
Appears in Collections:I3S - Artigo em Revista Científica Internacional

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