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Published in: Clinical Oral Investigations 9/2019

01-09-2019 | Original Article

Subgingival lipid A profile and endotoxin activity in periodontal health and disease

Authors: Alexander Strachan, Zoe Harrington, Clare McIlwaine, Matthew Jerreat, Louise A. Belfield, Aniko Kilar, Simon K. Jackson, Andrew Foey, Svetislav Zaric

Published in: Clinical Oral Investigations | Issue 9/2019

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Abstract

Objectives

Regulation of lipopolysaccharide (LPS) chemical composition, particularly its lipid A domain, is an important, naturally occurring mechanism that drives bacteria-host immune system interactions into either a symbiotic or pathogenic relationship. Members of the subgingival oral microbiota can critically modulate host immuno-inflammatory responses by synthesizing different LPS isoforms. The objectives of this study were to analyze subgingival lipid A profiles and endotoxin activities in periodontal health and disease and to evaluate the use of the recombinant factor C assay as a new, lipid A-based biosensor for personalized, point-of-care periodontal therapy.

Materials and methods

Subgingival plaque samples were collected from healthy individuals and chronic periodontitis patients before and after periodontal therapy. Chemical composition of subgingival lipid A moieties was determined by ESI-Mass Spectrometry. Endotoxin activity of subgingival LPS extracts was assessed using the recombinant factor C assay, and their inflammatory potential was examined in THP-1-derived macrophages by measuring TNF-α and IL-8 production.

Results

Characteristic lipid A molecular signatures, corresponding to over-acylated, bi-phosphorylated lipid A isoforms, were observed in diseased samples. Healthy and post-treatment samples were characterized by lower m/z peaks, related to under-acylated, hypo-phosphorylated lipid A structures. Endotoxin activity levels and inflammatory potentials of subgingival LPS extracts from periodontitis patients were significantly higher compared to healthy and post-treatment samples.

Conclusions

This is the first study to consider structure-function-clinical implications of different lipid A isoforms present in the subgingival niche and sheds new light on molecular pathogenic mechanisms of subgingival biofilm communities.

Clinical relevance

Subgingival endotoxin activity (determined by lipid A chemical composition) could be a reliable, bacterially derived biomarker and a risk assessment tool for personalized periodontal care.
Literature
1.
go back to reference Cafiero C, Matarasso S (2013) Predictive, preventive, personalised and participatory periodontology: ‘the 5Ps age’ has already started. EPMA J 4(1):16CrossRefPubMedPubMedCentral Cafiero C, Matarasso S (2013) Predictive, preventive, personalised and participatory periodontology: ‘the 5Ps age’ has already started. EPMA J 4(1):16CrossRefPubMedPubMedCentral
3.
go back to reference Meuric V, le Gall-David S, Boyer E, Acuña-Amador L, Martin B, Fong SB, Barloy-Hubler F, Bonnaure-Mallet M (2017) Signature of microbial dysbiosis in periodontitis. Appl Environ Microbiol 83(14) Meuric V, le Gall-David S, Boyer E, Acuña-Amador L, Martin B, Fong SB, Barloy-Hubler F, Bonnaure-Mallet M (2017) Signature of microbial dysbiosis in periodontitis. Appl Environ Microbiol 83(14)
4.
go back to reference Taguchi H, Aono Y, Kawato T, Asano M, Shimizu N, Saigusa T (2015) Intragingival injection of Porphyromonas gingivalis-derived lipopolysaccharide induces a transient increase in gingival tumour necrosis factor-alpha, but not interleukin-6, in anaesthetised rats. Int J Oral Sci 7(3):155–160CrossRefPubMedPubMedCentral Taguchi H, Aono Y, Kawato T, Asano M, Shimizu N, Saigusa T (2015) Intragingival injection of Porphyromonas gingivalis-derived lipopolysaccharide induces a transient increase in gingival tumour necrosis factor-alpha, but not interleukin-6, in anaesthetised rats. Int J Oral Sci 7(3):155–160CrossRefPubMedPubMedCentral
5.
go back to reference Jain S, Darveau RP (2010) Contribution of Porphyromonas gingivalis lipopolysaccharide to periodontitis. Periodontol 54(1):53–70CrossRef Jain S, Darveau RP (2010) Contribution of Porphyromonas gingivalis lipopolysaccharide to periodontitis. Periodontol 54(1):53–70CrossRef
6.
go back to reference Steimle A, Gronbach K, Beifuss B, Schäfer A, Harmening R, Bender A, Maerz JK, Lange A, Michaelis L, Maurer A, Menz S, McCoy K, Autenrieth IB, Kalbacher H, Frick JS (2016) Symbiotic gut commensal bacteria act as host cathepsin S activity regulators. J Autoimmun 75:82–95CrossRefPubMed Steimle A, Gronbach K, Beifuss B, Schäfer A, Harmening R, Bender A, Maerz JK, Lange A, Michaelis L, Maurer A, Menz S, McCoy K, Autenrieth IB, Kalbacher H, Frick JS (2016) Symbiotic gut commensal bacteria act as host cathepsin S activity regulators. J Autoimmun 75:82–95CrossRefPubMed
9.
go back to reference Rossi O, Pesce I, Giannelli C, Aprea S, Caboni M, Citiulo F, Valentini S, Ferlenghi I, MacLennan CA, D'Oro U, Saul A, Gerke C (2014) Modulation of endotoxicity of Shigella generalized modules for membrane antigens (GMMA) by genetic lipid A modifications: relative activation of TLR4 and TLR2 pathways in different mutants. J Biol Chem 289(36):24922–24935CrossRefPubMedPubMedCentral Rossi O, Pesce I, Giannelli C, Aprea S, Caboni M, Citiulo F, Valentini S, Ferlenghi I, MacLennan CA, D'Oro U, Saul A, Gerke C (2014) Modulation of endotoxicity of Shigella generalized modules for membrane antigens (GMMA) by genetic lipid A modifications: relative activation of TLR4 and TLR2 pathways in different mutants. J Biol Chem 289(36):24922–24935CrossRefPubMedPubMedCentral
10.
go back to reference Coats SR, Pham TTT, Bainbridge BW, Reife RA, Darveau RP (2005) MD-2 mediates the ability of tetra-acylated and penta-acylated lipopolysaccharides to antagonize Escherichia coli lipopolysaccharide at the TLR4 signaling complex. J Immunol 175(7):4490–4498CrossRefPubMed Coats SR, Pham TTT, Bainbridge BW, Reife RA, Darveau RP (2005) MD-2 mediates the ability of tetra-acylated and penta-acylated lipopolysaccharides to antagonize Escherichia coli lipopolysaccharide at the TLR4 signaling complex. J Immunol 175(7):4490–4498CrossRefPubMed
11.
go back to reference Herath TD et al (2013) Tetra- and penta-acylated lipid A structures of Porphyromonas gingivalis LPS differentially activate TLR4-mediated NF-kappaB signal transduction cascade and immuno-inflammatory response in human gingival fibroblasts. PLoS One 8(3):e58496CrossRefPubMedPubMedCentral Herath TD et al (2013) Tetra- and penta-acylated lipid A structures of Porphyromonas gingivalis LPS differentially activate TLR4-mediated NF-kappaB signal transduction cascade and immuno-inflammatory response in human gingival fibroblasts. PLoS One 8(3):e58496CrossRefPubMedPubMedCentral
12.
go back to reference To TT et al (2015) Subgingival plaque in periodontal health antagonizes at Toll-like receptor 4 and inhibits E-selectin expression on endothelial cells. Infect Immun 84(1):120–126CrossRefPubMedPubMedCentral To TT et al (2015) Subgingival plaque in periodontal health antagonizes at Toll-like receptor 4 and inhibits E-selectin expression on endothelial cells. Infect Immun 84(1):120–126CrossRefPubMedPubMedCentral
13.
go back to reference Coats SR, Jones JW, Do CT, Braham PH, Bainbridge BW, To TT, Goodlett DR, Ernst RK, Darveau RP (2009) Human Toll-like receptor 4 responses to P. gingivalis are regulated by lipid A 1- and 4′-phosphatase activities. Cell Microbiol 11(11):1587–1599CrossRefPubMedPubMedCentral Coats SR, Jones JW, Do CT, Braham PH, Bainbridge BW, To TT, Goodlett DR, Ernst RK, Darveau RP (2009) Human Toll-like receptor 4 responses to P. gingivalis are regulated by lipid A 1- and 4′-phosphatase activities. Cell Microbiol 11(11):1587–1599CrossRefPubMedPubMedCentral
15.
go back to reference Hajishengallis G, Lamont RJ (2012) Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology. Mol Oral Microbiol 27(6):409–419CrossRefPubMedPubMedCentral Hajishengallis G, Lamont RJ (2012) Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology. Mol Oral Microbiol 27(6):409–419CrossRefPubMedPubMedCentral
18.
go back to reference Slocum C, Coats SR, Hua N, Kramer C, Papadopoulos G, Weinberg EO, Gudino CV, Hamilton JA, Darveau RP, Genco CA (2014) Distinct lipid a moieties contribute to pathogen-induced site-specific vascular inflammation. PLoS Pathog 10(7):e1004215CrossRefPubMedPubMedCentral Slocum C, Coats SR, Hua N, Kramer C, Papadopoulos G, Weinberg EO, Gudino CV, Hamilton JA, Darveau RP, Genco CA (2014) Distinct lipid a moieties contribute to pathogen-induced site-specific vascular inflammation. PLoS Pathog 10(7):e1004215CrossRefPubMedPubMedCentral
19.
go back to reference Zenobia C, Hasturk H, Nguyen D, van Dyke TE, Kantarci A, Darveau RP (2014) Porphyromonas gingivalis lipid A phosphatase activity is critical for colonization and increasing the commensal load in the rabbit ligature model. Infect Immun 82(2):650–659CrossRefPubMedPubMedCentral Zenobia C, Hasturk H, Nguyen D, van Dyke TE, Kantarci A, Darveau RP (2014) Porphyromonas gingivalis lipid A phosphatase activity is critical for colonization and increasing the commensal load in the rabbit ligature model. Infect Immun 82(2):650–659CrossRefPubMedPubMedCentral
20.
go back to reference Posch G, Andrukhov O, Vinogradov E, Lindner B, Messner P, Holst O, Schäffer C (2013) Structure and immunogenicity of the rough-type lipopolysaccharide from the periodontal pathogen Tannerella forsythia. Clin Vaccine Immunol 20(6):945–953CrossRefPubMedPubMedCentral Posch G, Andrukhov O, Vinogradov E, Lindner B, Messner P, Holst O, Schäffer C (2013) Structure and immunogenicity of the rough-type lipopolysaccharide from the periodontal pathogen Tannerella forsythia. Clin Vaccine Immunol 20(6):945–953CrossRefPubMedPubMedCentral
21.
go back to reference Masoud H et al (1991) Investigation of the structure of lipid A from Actinobacillus actinomycetemcomitans strain Y4 and human clinical isolate PO 1021-7. Eur J Biochem 200(3):775–781CrossRefPubMed Masoud H et al (1991) Investigation of the structure of lipid A from Actinobacillus actinomycetemcomitans strain Y4 and human clinical isolate PO 1021-7. Eur J Biochem 200(3):775–781CrossRefPubMed
22.
go back to reference Asai Y, Makimura Y, Kawabata A, Ogawa T (2007) Soluble CD14 discriminates slight structural differences between lipid as that lead to distinct host cell activation. J Immunol 179(11):7674–7683CrossRefPubMed Asai Y, Makimura Y, Kawabata A, Ogawa T (2007) Soluble CD14 discriminates slight structural differences between lipid as that lead to distinct host cell activation. J Immunol 179(11):7674–7683CrossRefPubMed
23.
go back to reference John CM, Phillips NJ, Din R, Liu M, Rosenqvist E, Høiby EA, Stein DC, Jarvis GA (2016) Lipooligosaccharide structures of invasive and carrier isolates of Neisseria meningitidis are correlated with pathogenicity and carriage. J Biol Chem 291(7):3224–3238CrossRefPubMed John CM, Phillips NJ, Din R, Liu M, Rosenqvist E, Høiby EA, Stein DC, Jarvis GA (2016) Lipooligosaccharide structures of invasive and carrier isolates of Neisseria meningitidis are correlated with pathogenicity and carriage. J Biol Chem 291(7):3224–3238CrossRefPubMed
24.
go back to reference SenGupta S, Hittle LE, Ernst RK, Uriarte SM, Mitchell TC (2016) A Pseudomonas aeruginosa hepta-acylated lipid A variant associated with cystic fibrosis selectively activates human neutrophils. J Leukoc Biol 100(5):1047–1059CrossRefPubMedPubMedCentral SenGupta S, Hittle LE, Ernst RK, Uriarte SM, Mitchell TC (2016) A Pseudomonas aeruginosa hepta-acylated lipid A variant associated with cystic fibrosis selectively activates human neutrophils. J Leukoc Biol 100(5):1047–1059CrossRefPubMedPubMedCentral
25.
go back to reference Cullen TW, Giles DK, Wolf LN, Ecobichon C, Boneca IG, Trent MS (2011) Helicobacter pylori versus the host: remodeling of the bacterial outer membrane is required for survival in the gastric mucosa. PLoS Pathog 7(12):e1002454CrossRefPubMedPubMedCentral Cullen TW, Giles DK, Wolf LN, Ecobichon C, Boneca IG, Trent MS (2011) Helicobacter pylori versus the host: remodeling of the bacterial outer membrane is required for survival in the gastric mucosa. PLoS Pathog 7(12):e1002454CrossRefPubMedPubMedCentral
26.
go back to reference Socransky SS, Haffajee AD, Teles R, Wennstrom JL, Lindhe J, Bogren A, Hasturk H, van Dyke T, Wang X, Goodson JM (2013) Effect of periodontal therapy on the subgingival microbiota over a 2-year monitoring period. I. Overall effect and kinetics of change. J Clin Periodontol 40(8):771–780CrossRefPubMedPubMedCentral Socransky SS, Haffajee AD, Teles R, Wennstrom JL, Lindhe J, Bogren A, Hasturk H, van Dyke T, Wang X, Goodson JM (2013) Effect of periodontal therapy on the subgingival microbiota over a 2-year monitoring period. I. Overall effect and kinetics of change. J Clin Periodontol 40(8):771–780CrossRefPubMedPubMedCentral
27.
go back to reference Feres M, Teles F, Teles R, Figueiredo LC, Faveri M (2016) The subgingival periodontal microbiota of the aging mouth. Periodontol 72(1):30–53CrossRef Feres M, Teles F, Teles R, Figueiredo LC, Faveri M (2016) The subgingival periodontal microbiota of the aging mouth. Periodontol 72(1):30–53CrossRef
28.
go back to reference Ding JL, Ho B (2010) Endotoxin detection--from limulus amebocyte lysate to recombinant factor C. Subcell Biochem 53:187–208CrossRefPubMed Ding JL, Ho B (2010) Endotoxin detection--from limulus amebocyte lysate to recombinant factor C. Subcell Biochem 53:187–208CrossRefPubMed
29.
go back to reference Gutsmann T, Howe J, Zähringer U, Garidel P, Schromm AB, Koch MHJ, Fujimoto Y, Fukase K, Moriyon I, Martínez-de-Tejada G, Brandenburg K (2010) Structural prerequisites for endotoxic activity in the Limulus test as compared to cytokine production in mononuclear cells. Innate Immun 16(1):39–47CrossRefPubMed Gutsmann T, Howe J, Zähringer U, Garidel P, Schromm AB, Koch MHJ, Fujimoto Y, Fukase K, Moriyon I, Martínez-de-Tejada G, Brandenburg K (2010) Structural prerequisites for endotoxic activity in the Limulus test as compared to cytokine production in mononuclear cells. Innate Immun 16(1):39–47CrossRefPubMed
30.
go back to reference Gronbach K, Flade I, Holst O, Lindner B, Ruscheweyh HJ, Wittmann A, Menz S, Schwiertz A, Adam P, Stecher B, Josenhans C, Suerbaum S, Gruber AD, Kulik A, Huson D, Autenrieth IB, Frick JS (2014) Endotoxicity of lipopolysaccharide as a determinant of T-cell-mediated colitis induction in mice. Gastroenterology 146(3):765–775CrossRefPubMed Gronbach K, Flade I, Holst O, Lindner B, Ruscheweyh HJ, Wittmann A, Menz S, Schwiertz A, Adam P, Stecher B, Josenhans C, Suerbaum S, Gruber AD, Kulik A, Huson D, Autenrieth IB, Frick JS (2014) Endotoxicity of lipopolysaccharide as a determinant of T-cell-mediated colitis induction in mice. Gastroenterology 146(3):765–775CrossRefPubMed
31.
Metadata
Title
Subgingival lipid A profile and endotoxin activity in periodontal health and disease
Authors
Alexander Strachan
Zoe Harrington
Clare McIlwaine
Matthew Jerreat
Louise A. Belfield
Aniko Kilar
Simon K. Jackson
Andrew Foey
Svetislav Zaric
Publication date
01-09-2019
Publisher
Springer Berlin Heidelberg
Published in
Clinical Oral Investigations / Issue 9/2019
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-018-2771-9

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