title: 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.affiliation: Department of Conservative Dentistry, Semmelweis University, Budapest, Hungary.|Institute of Human Physiology and Clinical Experimental Research, Semmelweis University.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Lohinai
authors.affiliation: Department of Oral Biology, Semmelweis University.
authors.forename: Beata
authors.initials: B
authors.lastname: Keremi
authors.affiliation: Department of Pharmacodynamics, Semmelweis University.
authors.forename: Eva
authors.initials: E
authors.lastname: Szöko
authors.affiliation: Department of Pharmacodynamics, Semmelweis University.
authors.forename: Tamás
authors.initials: T
authors.lastname: Tábi
authors.affiliation: Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX.
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabo
authors.affiliation: 2nd Department of Internal Medicine, Semmelweis University.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Tulassay
authors.affiliation: Department of Chemistry, Georgia Southern University, Statesboro, GA.
authors.forename: John C
authors.initials: JC
authors.lastname: DiCesare
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
authors.forename: Carole A
authors.initials: CA
authors.lastname: Davis
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Collins
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
authors.forename: Martin
authors.initials: M
authors.lastname: Levine
mesh_terms: D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects; D002103:Cadaverine / Q000032:analysis; D002262:Carboxy-Lyases / Q000032:analysis / Q000037:antagonists & inhibitors*; D003774:Dental Plaque Index; D016124:Eikenella corrodens / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005883:Gingival Crevicular Fluid / Q000737:chemistry / Q000187:drug effects; D005891:Gingivitis / Q000382:microbiology* / Q000517:prevention & control; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009067:Mouthwashes / Q000627:therapeutic use; D010518:Periodontitis / Q000382:microbiology / Q000517:prevention & control; D012463:Saliva / Q000737:chemistry; D014148:Tranexamic Acid / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D009067:Mouthwashes; D014148:Tranexamic Acid; D002262:Carboxy-Lyases; C021520:lysine decarboxylase; D002103:Cadaverine
keywords: Biomarkers; dental plaque; drug delivery systems; gingival crevicular fluid; gingivitis; oral hygiene.; pharmacological