Novel Campylobacter concisus lipooligosaccharide is a determinant of inflammatory potential and virulence
The pathogenicity of Campylobacter concisus, increasingly found in the human gastrointestinal (GI) tract, is unclear. Some studies indicate that its role in GI conditions has been underestimated, whereas others suggest that the organism has a commensal-like phenotype. For the enteropathogen C. jejun...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-10-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S002222752034181X |
| _version_ | 1831665373090414592 |
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| author | Katja Brunner Constance M. John Nancy J. Phillips Dagmar G. Alber Matthew R. Gemmell Richard Hansen Hans L. Nielsen Georgina L. Hold Mona Bajaj-Elliott Gary A. Jarvis |
| author_facet | Katja Brunner Constance M. John Nancy J. Phillips Dagmar G. Alber Matthew R. Gemmell Richard Hansen Hans L. Nielsen Georgina L. Hold Mona Bajaj-Elliott Gary A. Jarvis |
| author_sort | Katja Brunner |
| collection | DOAJ |
| description | The pathogenicity of Campylobacter concisus, increasingly found in the human gastrointestinal (GI) tract, is unclear. Some studies indicate that its role in GI conditions has been underestimated, whereas others suggest that the organism has a commensal-like phenotype. For the enteropathogen C. jejuni, the lipooligosaccharide (LOS) is a main driver of virulence. We investigated the LOS structure of four C. concisus clinical isolates and correlated the inflammatory potential of each isolate with bacterial virulence. Mass spectrometric analyses of lipid A revealed a novel hexa-acylated diglucosamine moiety with two or three phosphoryl substituents. Molecular and fragment ion analysis indicated that the oligosaccharide portion of the LOS had only a single phosphate and lacked phosphoethanolamine and sialic acid substitution, which are hallmarks of the C. jejuni LOS. Consistent with our structural findings, C. concisus LOS and live bacteria induced less TNF-α secretion in human monocytes than did C. jejuni. Furthermore, the C. concisus bacteria were less virulent than C. jejuni in a Galleria mellonella infection model. The correlation of the novel lipid A structure, decreased phosphorylation, and lack of sialylation along with reduced inflammatory potential and virulence support the significance of the LOS as a determinant in the relative pathogenicity of C. concisus. |
| first_indexed | 2024-12-19T19:33:31Z |
| format | Article |
| id | doaj.art-7a827cf87a674a91b5b8e8d9711f5d22 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-19T19:33:31Z |
| publishDate | 2018-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-7a827cf87a674a91b5b8e8d9711f5d222022-12-21T20:08:32ZengElsevierJournal of Lipid Research0022-22752018-10-01591018931905Novel Campylobacter concisus lipooligosaccharide is a determinant of inflammatory potential and virulenceKatja Brunner0Constance M. John1Nancy J. Phillips2Dagmar G. Alber3Matthew R. Gemmell4Richard Hansen5Hans L. Nielsen6Georgina L. Hold7Mona Bajaj-Elliott8Gary A. Jarvis9To whom correspondence should be addressed.; To whom correspondence should be addressed.; Infection, Immunity and Inflammation Programme, University College London Great Ormond Street Institute of Child Health, London, United KingdomTo whom correspondence should be addressed.; Center for Immunochemistry, Veterans Affairs Medical Center, San Francisco, CA; Department of Laboratory Medicine University of California, San Francisco, CADepartment of Pharmaceutical Chemistry, University of California, San Francisco, CAInfection, Immunity and Inflammation Programme, University College London Great Ormond Street Institute of Child Health, London, United KingdomCenter for Genome-Enabled Biology and Medicine, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United KingdomDepartment of Paediatric Gastroenterology, Royal Hospital for Children, Glasgow, United KingdomDepartment of Infectious Diseases Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, DenmarkSt George and Sutherland Clinical School, University of New South Wales, Sydney, AustraliaInfection, Immunity and Inflammation Programme, University College London Great Ormond Street Institute of Child Health, London, United KingdomTo whom correspondence should be addressed.; Center for Immunochemistry, Veterans Affairs Medical Center, San Francisco, CA; Department of Laboratory Medicine University of California, San Francisco, CA; To whom correspondence should be addressed.The pathogenicity of Campylobacter concisus, increasingly found in the human gastrointestinal (GI) tract, is unclear. Some studies indicate that its role in GI conditions has been underestimated, whereas others suggest that the organism has a commensal-like phenotype. For the enteropathogen C. jejuni, the lipooligosaccharide (LOS) is a main driver of virulence. We investigated the LOS structure of four C. concisus clinical isolates and correlated the inflammatory potential of each isolate with bacterial virulence. Mass spectrometric analyses of lipid A revealed a novel hexa-acylated diglucosamine moiety with two or three phosphoryl substituents. Molecular and fragment ion analysis indicated that the oligosaccharide portion of the LOS had only a single phosphate and lacked phosphoethanolamine and sialic acid substitution, which are hallmarks of the C. jejuni LOS. Consistent with our structural findings, C. concisus LOS and live bacteria induced less TNF-α secretion in human monocytes than did C. jejuni. Furthermore, the C. concisus bacteria were less virulent than C. jejuni in a Galleria mellonella infection model. The correlation of the novel lipid A structure, decreased phosphorylation, and lack of sialylation along with reduced inflammatory potential and virulence support the significance of the LOS as a determinant in the relative pathogenicity of C. concisus.http://www.sciencedirect.com/science/article/pii/S002222752034181Xcytokinesglycolipidsinflammationlipid Amass spectrometrymonocytes |
| spellingShingle | Katja Brunner Constance M. John Nancy J. Phillips Dagmar G. Alber Matthew R. Gemmell Richard Hansen Hans L. Nielsen Georgina L. Hold Mona Bajaj-Elliott Gary A. Jarvis Novel Campylobacter concisus lipooligosaccharide is a determinant of inflammatory potential and virulence Journal of Lipid Research cytokines glycolipids inflammation lipid A mass spectrometry monocytes |
| title | Novel Campylobacter concisus lipooligosaccharide is a determinant of inflammatory potential and virulence |
| title_full | Novel Campylobacter concisus lipooligosaccharide is a determinant of inflammatory potential and virulence |
| title_fullStr | Novel Campylobacter concisus lipooligosaccharide is a determinant of inflammatory potential and virulence |
| title_full_unstemmed | Novel Campylobacter concisus lipooligosaccharide is a determinant of inflammatory potential and virulence |
| title_short | Novel Campylobacter concisus lipooligosaccharide is a determinant of inflammatory potential and virulence |
| title_sort | novel campylobacter concisus lipooligosaccharide is a determinant of inflammatory potential and virulence |
| topic | cytokines glycolipids inflammation lipid A mass spectrometry monocytes |
| url | http://www.sciencedirect.com/science/article/pii/S002222752034181X |
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