title: Helicobacter pylori chronic infection and mucosal inflammation switches the human gastric glycosylation pathways.
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.
authors.affiliation: 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.
authors.forename: Ana
authors.initials: A
authors.lastname: Magalhães
authors.affiliation: 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.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Marcos-Pinto
authors.affiliation: Complex Carbohydrate Research Center and Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA.
authors.forename: Alison V
authors.initials: AV
authors.lastname: Nairn
authors.affiliation: Complex Carbohydrate Research Center and Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA.
authors.forename: Mitche
authors.initials: M
authors.lastname: Dela Rosa
authors.affiliation: 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.
authors.forename: Rui M
authors.initials: RM
authors.lastname: Ferreira
authors.affiliation: 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.
authors.forename: Susana
authors.initials: S
authors.lastname: Junqueira-Neto
authors.affiliation: 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.
authors.forename: Daniela
authors.initials: D
authors.lastname: Freitas
authors.affiliation: 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.
authors.forename: Joana
authors.initials: J
authors.lastname: Gomes
authors.affiliation: 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.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Oliveira
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal.
authors.forename: Marta R
authors.initials: MR
authors.lastname: Santos
authors.affiliation: 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.
authors.forename: Nuno T
authors.initials: NT
authors.lastname: Marcos
authors.affiliation: Department of Pathology, Centro Hospitalar São João, Porto, Portugal; Centro Hospitalar Vila Nova de Gaia/Espinho, Portugal.
authors.forename: Wen
authors.initials: W
authors.lastname: Xiaogang
authors.affiliation: 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.
authors.forename: Céu
authors.initials: C
authors.lastname: Figueiredo
authors.affiliation: 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.
authors.forename: Carla
authors.initials: C
authors.lastname: Oliveira
authors.affiliation: Medical Faculty, University of Porto, Portugal; Gastroenterology Department, IPO Porto, Portugal; CIDES/CINTESIS, University of Porto, Portugal.
authors.forename: Mário
authors.initials: M
authors.lastname: Dinis-Ribeiro
authors.affiliation: 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.
authors.forename: Fátima
authors.initials: F
authors.lastname: Carneiro
authors.affiliation: Complex Carbohydrate Research Center and Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA.
authors.forename: Kelley W
authors.initials: KW
authors.lastname: Moremen
authors.affiliation: 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.
authors.forename: Leonor
authors.initials: L
authors.lastname: David
authors.affiliation: 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.
authors.forename: Celso A
authors.initials: CA
authors.lastname: Reis
keywords: Chronic infection; Glycophenotype; Helicobacter pylori; Sialic acid-binding adhesin