A novel O-linked glycan modulates Campylobacter jejuni major outer membrane protein-mediated adhesion to human histo-blood group antigens and chicken colonization
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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
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Royal Society
2014
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| Online Access: | https://eprints.nottingham.ac.uk/34890/ |
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| author | Mahdavi, Jafar Pirinccioglu, Necmettin Oldfield, Neil J. Carlsohn, Elisabet Stoof, Jeroen Aslam, Akhmed Self, Tim Cawthraw, Shaun A. Petrovska, Liljana Colborne, Natalie Sihlbom, Carina Boren, Thomas Wooldridge, Karl G. Ala'Aldeen, Dlawer A.A. |
| author_facet | Mahdavi, Jafar Pirinccioglu, Necmettin Oldfield, Neil J. Carlsohn, Elisabet Stoof, Jeroen Aslam, Akhmed Self, Tim Cawthraw, Shaun A. Petrovska, Liljana Colborne, Natalie Sihlbom, Carina Boren, Thomas Wooldridge, Karl G. Ala'Aldeen, Dlawer A.A. |
| author_sort | Mahdavi, Jafar |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:24:25Z |
| format | Article |
| id | nottingham-34890 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:24:25Z |
| publishDate | 2014 |
| publisher | Royal Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-348902020-05-04T16:41:27Z https://eprints.nottingham.ac.uk/34890/ 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 Pirinccioglu, Necmettin Oldfield, Neil J. Carlsohn, Elisabet Stoof, Jeroen Aslam, Akhmed Self, Tim Cawthraw, Shaun A. Petrovska, Liljana Colborne, Natalie Sihlbom, Carina Boren, Thomas Wooldridge, Karl G. Ala'Aldeen, Dlawer A.A. 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. Royal Society 2014-01-22 Article PeerReviewed Mahdavi, Jafar, Pirinccioglu, Necmettin, Oldfield, Neil J., Carlsohn, Elisabet, Stoof, Jeroen, Aslam, Akhmed, Self, Tim, Cawthraw, Shaun A., Petrovska, Liljana, Colborne, Natalie, Sihlbom, Carina, Boren, Thomas, 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 Campylobacter jejuni histo-blood group antigens FlaA major outer membrane protein O-glycosylation biofilm http://rsob.royalsocietypublishing.org/content/4/1/130202 doi:10.1098/rsob.130202 doi:10.1098/rsob.130202 |
| spellingShingle | Campylobacter jejuni histo-blood group antigens FlaA major outer membrane protein O-glycosylation biofilm Mahdavi, Jafar Pirinccioglu, Necmettin Oldfield, Neil J. Carlsohn, Elisabet Stoof, Jeroen Aslam, Akhmed Self, Tim Cawthraw, Shaun A. Petrovska, Liljana Colborne, Natalie Sihlbom, Carina Boren, Thomas Wooldridge, Karl G. Ala'Aldeen, Dlawer A.A. A novel O-linked glycan modulates Campylobacter jejuni major outer membrane protein-mediated adhesion to human histo-blood group antigens and chicken colonization |
| title | A novel O-linked glycan modulates Campylobacter jejuni major outer membrane protein-mediated adhesion to human histo-blood group antigens and chicken colonization |
| title_full | A novel O-linked glycan modulates Campylobacter jejuni major outer membrane protein-mediated adhesion to human histo-blood group antigens and chicken colonization |
| title_fullStr | A novel O-linked glycan modulates Campylobacter jejuni major outer membrane protein-mediated adhesion to human histo-blood group antigens and chicken colonization |
| title_full_unstemmed | A novel O-linked glycan modulates Campylobacter jejuni major outer membrane protein-mediated adhesion to human histo-blood group antigens and chicken colonization |
| title_short | A novel O-linked glycan modulates Campylobacter jejuni major outer membrane protein-mediated adhesion to human histo-blood group antigens and chicken colonization |
| title_sort | novel o-linked glycan modulates campylobacter jejuni major outer membrane protein-mediated adhesion to human histo-blood group antigens and chicken colonization |
| topic | Campylobacter jejuni histo-blood group antigens FlaA major outer membrane protein O-glycosylation biofilm |
| url | https://eprints.nottingham.ac.uk/34890/ https://eprints.nottingham.ac.uk/34890/ https://eprints.nottingham.ac.uk/34890/ |