A novel phosphoglycerol serine-glycine lipodipeptide of Porphyromonas gingivalis is a TLR2 ligand

Frank C Nichols; Robert B Clark; Mark W Maciejewski; Anthony A Provatas; Jeremy L Balsbaugh; Floyd E Dewhirst; Michael B Smith; Amanda Rahmlow

doi:10.1194/jlr.RA120000951

A novel phosphoglycerol serine-glycine lipodipeptide of Porphyromonas gingivalis is a TLR2 ligand

J Lipid Res. 2020 Dec;61(12):1645-1657. doi: 10.1194/jlr.RA120000951. Epub 2020 Sep 10.

Authors

Frank C Nichols¹, Robert B Clark², Mark W Maciejewski³, Anthony A Provatas⁴, Jeremy L Balsbaugh⁵, Floyd E Dewhirst⁶, Michael B Smith⁷, Amanda Rahmlow⁸

Affiliations

¹ Department of Oral Health and Diagnostic Sciences, University of Connecticut School of Dental Medicine, Farmington, CT, USA. Electronic address: nichols@uchc.edu.
² Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, USA; Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, USA.
³ Department of Molecular Biology and Biophysics, University of Connecticut School of Medicine, Farmington, CT, USA.
⁴ Center for Environmental Sciences and Engineering, University of Connecticut, Storrs, CT, USA.
⁵ Center for Open Research Resources and Equipment, University of Connecticut, Storrs, CT, USA.
⁶ Department of Microbiology, The Forsyth Institute, Cambridge, MA, USA; Department of Oral Medicine, Harvard School of Dental Medicine, Boston, MA, USA.
⁷ Department of Chemistry, University of Connecticut, Storrs, CT USA.
⁸ Department of Oral Health and Diagnostic Sciences, University of Connecticut School of Dental Medicine, Farmington, CT, USA.

Abstract

Porphyromonas gingivalis is a Gram-negative anaerobic periodontal microorganism strongly associated with tissue-destructive processes in human periodontitis. Following oral infection with P. gingivalis, the periodontal bone loss in mice is reported to require the engagement of Toll-like receptor 2 (TLR2). Serine-glycine lipodipeptide or glycine aminolipid classes of P. gingivalis engage human and mouse TLR2, but a novel lipid class reported here is considerably more potent in engaging TLR2 and the heterodimer receptor TLR2/TLR6. The novel lipid class, termed Lipid 1256, consists of a diacylated phosphoglycerol moiety linked to a serine-glycine lipodipeptide previously termed Lipid 654. Lipid 1256 is approximately 50-fold more potent in engaging TLR2 than the previously reported serine-glycine lipid classes. Lipid 1256 also stimulates cytokine secretory responses from peripheral blood monocytes and is recovered in selected oral and intestinal Bacteroidetes organisms. Therefore, these findings suggest that Lipid 1256 may be a microbial TLR2 ligand relevant to chronic periodontitis in humans.

Keywords: Bacteroidetes; high-performance liquid chromatography; lipid signaling; monocytes; periodontitis; phospholipids; tandem mass spectrometry.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Glycine*
Humans
Ligands
Lipopeptides / chemistry
Lipopeptides / metabolism*
Mice
Porphyromonas gingivalis / metabolism*
Serine*
Toll-Like Receptor 2 / metabolism*

Substances

Ligands
Lipopeptides
TLR2 protein, human
Toll-Like Receptor 2
Serine
Glycine

Grants and funding

R01 DE027642/DE/NIDCR NIH HHS/United States