Helicobacter pylori modulates the gastric mucosa glycosylation for long term-colonization

Authors and Affiliations:

Ana Magalhães^a,b, Ricardo Marcos-Pinto^c,d,e, Alison V. Nairn^f, Mitche dela Rosa^f, Rui M. Ferreira^a,b, Susana Junqueira-Neto^a,b, Daniela Freitas^a,b, Joana Gomes^a,b, Patrícia Oliveira^a,b, Marta R. Santos^b, Nuno T. Marcos^a,b,g, Wen Xiaogang^h,i, Céu Figueiredo^a,b,e, Carla Oliveira^a,b,e, Mário Dinis-Ribeiro^e,j,k, Fátima Carneiro^a,b,e,h, Kelley W. Moremen^f, Leonor David^a,b,e, Celso A. Reis^a,b,d,e,*

^aInstituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal, Institute for Research and Innovation in Health, University of Porto, Portugal

^bInstitute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Portugal

^cCentro Hospitalar do Porto (CHP), Gastroenterology Department, Portugal

^dInstitute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Portugal

^eMedical Faculty, University of Porto, Portugal

^fComplex Carbohydrate Research Center and Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA

^gSection of Health Sciences, University of Aveiro, Portugal

^hDepartment of Pathology, Centro Hospitalar São João, Porto, Portugal

ⁱCentro Hospitalar Vila Nova de Gaia/Espinho, Portugal

^jGastroenterology Department, IPO Porto, Portugal

^kCIDES/CINTESIS, University of Porto, Portugal

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.

Journal: BBA Molecular Basis of Disease

Link: http://www.sciencedirect.com/science/article/pii/S0925443915001933