A novel O-linked glycan modulates Campylobacter jejuni major outer membrane protein-mediated adhesion to human histo-blood group antigens and chicken colonization

Mahdavi, Jafar and Pirinccioglu, Necmettin and Oldfield, Neil J. and Carlsohn, Elisabet and Stoof, Jeroen and Aslam, Akhmed and Self, Tim and Cawthraw, Shaun A. and Petrovska, Liljana and Colborne, Natalie and Sihlbom, Carina and Boren, Thomas and Wooldridge, Karl G. and Ala'Aldeen, Dlawer A.A. (2014) A novel O-linked glycan modulates Campylobacter jejuni major outer membrane protein-mediated adhesion to human histo-blood group antigens and chicken colonization. Open Biology, 4 (1). 130202/1-130202/15. ISSN 2046-2441

[img]
Preview
PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Available under Licence Creative Commons Attribution.
Download (1MB) | Preview

Abstract

Campylobacter jejuni is an important cause of human foodborne gastroenteritis; strategies to prevent infection are hampered by a poor understanding of the complex interactions between host and pathogen. Previous work showed that C. jejuni could bind human histo-blood group antigens (BgAgs) in vitro and that BgAgs could inhibit the binding of C. jejuni to human intestinal mucosa ex vivo. Here, the major flagella subunit protein (FlaA) and the major outer membrane protein (MOMP) were identified as BgAg-binding adhesins in C. jejuni NCTC11168. Significantly, the MOMP was shown to be O-glycosylated at Thr268; previously only flagellin proteins were known to be O-glycosylated in C. jejuni. Substitution of MOMP Thr268 led to significantly reduced binding to BgAgs. The O-glycan moiety was characterized as Gal(β1–3)-GalNAc(β1–4)-GalNAc(β1–4)-GalNAcα1-Thr268; modelling suggested that O-glycosylation has a notable effect on the conformation of MOMP and this modulates BgAg-binding capacity. Glycosylation of MOMP at Thr268 promoted cell-to-cell binding, biofilm formation and adhesion to Caco-2 cells, and was required for the optimal colonization of chickens by C. jejuni, confirming the significance of this O-glycosylation in pathogenesis.

Item Type: Article
Keywords: Campylobacter jejuni, histo-blood group antigens, FlaA, major outer membrane protein, O-glycosylation, biofilm
Schools/Departments: University of Nottingham UK Campus > Faculty of Medicine and Health Sciences > School of Life Sciences
Identification Number: https://doi.org/10.1098/rsob.130202
Depositing User: Eprints, Support
Date Deposited: 12 Jul 2016 08:41
Last Modified: 13 Sep 2016 22:57
URI: http://eprints.nottingham.ac.uk/id/eprint/34890

Actions (Archive Staff Only)

Edit View Edit View