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J Lipid Res. 2018 Oct;59(10):1893-1905. doi: 10.1194/jlr.M085860. Epub 2018 Jul 26.

Novel Campylobacter concisus lipooligosaccharide is a determinant of inflammatory potential and virulence.

Author information

1
Infection, Immunity and Inflammation Programme, University College London Great Ormond Street Institute of Child Health, London, United Kingdom.
2
Center for Immunochemistry, Veterans Affairs Medical Center, San Francisco, CA.
3
Department of Laboratory Medicine University of California, San Francisco, CA.
4
Department of Pharmaceutical Chemistry, University of California, San Francisco, CA.
5
Center for Genome-Enabled Biology and Medicine, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
6
Department of Paediatric Gastroenterology, Royal Hospital for Children, Glasgow, United Kingdom.
7
Department of Infectious Diseases Aalborg University Hospital, Aalborg, Denmark.
8
Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark.
9
St George and Sutherland Clinical School, University of New South Wales, Sydney, Australia.
10
Center for Immunochemistry, Veterans Affairs Medical Center, San Francisco, CA gary.jarvis@ucsf.edu.

Abstract

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.

KEYWORDS:

cytokines; glycolipids; inflammation; lipid A; mass spectrometry; monocytes; phosphorylation; toll-like receptors

PMID:
30049709
PMCID:
PMC6168313
DOI:
10.1194/jlr.M085860
[Indexed for MEDLINE]
Free PMC Article

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