Biofilm Lysine Decarboxylase, a New Therapeutic Target for Periodontal Inflammation.

Abstract

BACKGROUND:

Lysine, a nutritionally essential amino acid, enters the oral cavity in gingival crevicular fluid (GCF). During oral hygiene restriction (OHR), lysine decarboxylase (LDC) in dento-gingival biofilms converts lysine to cadaverine. Lysine depletion impairs the dental epithelial barrier to bacterial proinflammatory products. Antibodies to LDC from Eikenella corrodens (Ecor-LDC) inhibit LDC activity and retard gingival inflammation in beagle dogs. Whether E. corrodens is the major source of LDC in dental biofilms and whether the lysine analog tranexamic acid (TA) inhibits LDC activity, biofilm accumulation, and GCF exudation in a human gingivitis model were examined.

METHODS:

Antibodies raised in goats to LDC-rich extracts from E. corrodens cell surfaces were used to inhibit Ecor-LDC and detect it in biofilm extracts using Western blots. Ecor-LDC activity was measured at pH 4.0 to 11.0 and its TA dissociation constant (Ki) at pH 7.0. Young adults used a 5% or 10% TA mouthwash three times daily during OHR for 1 week.

RESULTS:

Ecor-LDC antibodies and TA inhibited biofilm LDC. Ki of TA for Ecor-LDC was 940 μM. TA reduced plaque index (PI) by downshifting the PI correlation with biofilm lysine content after OHR without TA. GCF was correspondingly suppressed. However, greater TA retention in saliva partially relieved GCF suppression but not biofilm lysine depletion.

CONCLUSIONS:

TA slightly inhibits LDC but strongly reduces biofilm by inhibiting bacterial lysine uptake. Unfortunately, TA may impair dental epithelial attachments by also inhibiting lysine transporter uptake. Ecor-LDC inhibitors other than lysine analogs may maintain sufficient lysine levels and attachment integrity to prevent periodontal inflammation.

• Authors: Zsolt Lohinai, Beata Keremi, Eva Szöko, Tamás Tábi, Csaba Szabo, Zsolt Tulassay, John C DiCesare, Carole A Davis, Lindsay M Collins, Martin Levine
• Journal: Journal of periodontology (J Periodontol) Vol. 86 Issue 10 Pg. 1176-84 (Oct 2015) ISSN: 1943-3670 [Electronic] United States
• PMID: 26110450 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Bacterial
• Enzyme Inhibitors
• Inflammation Mediators
• Mouthwashes
• Tranexamic Acid
• Carboxy-Lyases
• lysine decarboxylase
• Cadaverine

Topics

• Adult
• Aged
• Antibodies, Bacterial (pharmacology)
• Biofilms (drug effects)
• Cadaverine (analysis)
• Carboxy-Lyases (analysis, antagonists & inhibitors)
• Dental Plaque Index
• Eikenella corrodens (enzymology)
• Enzyme Inhibitors (pharmacology, therapeutic use)
• Female
• Gingival Crevicular Fluid (chemistry, drug effects)
• Gingivitis (microbiology, prevention & control)
• Humans
• Inflammation Mediators (metabolism)
• Male
• Middle Aged
• Mouthwashes (therapeutic use)
• Periodontitis (microbiology, prevention & control)
• Saliva (chemistry)
• Tranexamic Acid (pharmacology, therapeutic use)
• Young Adult