@article{20b21818b9484704bbcebe4d41629bfa,
title = "Novel Campylobacter concisus lipooligosaccharide is a determinant of inflammatory potential and virulence",
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 entero-pathogen 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- 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",
author = "Katja Brunner and John, {Constance M.} and Phillips, {Nancy J.} and Alber, {Dagmar G.} and Gemmell, {Matthew R.} and Richard Hansen and Nielsen, {Hans L.} and Hold, {Georgina L.} and Mona Bajaj-Elliott and Jarvis, {Gary A.}",
note = "Funding Information: This work was supported in part by Department of Veterans Affairs Merit Review award BX000727 (to G.A.J.). The authors also acknowledge National Institutes of Health National Center for Research Resources Shared Instrumentation Grant S10 RR029446 (to H. E. Witkowska) for acquisition of the Synapt G2 high-definition mass spectrometer, which is located at the University of California, San Francisco Sandler-Moore Mass Spectrometry Core Facility and supported by the Sandler Family Foundation, the Gordon and Betty Moore Foundation, National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA082103, and the Canary Foundation. G.A.J. is a recipient of the Senior Research Career Scientist award from the Department of Veterans Affairs. R.H. is funded by a Career Researcher Fellowship from NHS Research Scotland. The BISCUIT study was funded by a Clinical Academic Training Fellowship from the Chief Scientist Office (CAF/08/01). This is paper number 116 from the Center for Immunochemistry. The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. K.B. acknowledges funding from the Child Health Research Charitable Incorporated Organisation and the Bogue Fellowship for travel. The authors declare that they have no conflicts of interest with the contents of this article. Manuscript received 4 April 2018 and in revised form 29 June 2018. Published, JLR Papers in Press, July 26, 2018 DOI https://doi.org/10.1194/jlr.M085860 Publisher Copyright: {\textcopyright} 2018 American Society for Biochemistry and Molecular Biology Inc. All rights reserved.",
year = "2018",
doi = "10.1194/jlr.M085860",
language = "English",
volume = "59",
pages = "1893--1905",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "10",
}