title: Matrix Metalloproteinase Inhibitor as an Antimicrobial Agent to Eradicate Enterococcus faecalis Biofilm.
abstract: BACKGROUND
  Successful endodontic treatment outcomes require new strategies for the complete eradication of microbial biofilms in the root canal system. Matrix metalloproteinases (MMPs) are essential enzymes in microbial cell growth and homeostasis, and they require transition metal ion cofactors to function. Targeting MMP activity also preserves dentin collagen integrity. In this study, 1,10-phenanthroline-5,6-dione (Phendione), a metal chelator, was tested as a potentially novel antimicrobial agent against Enterococcus faecalis and inhibitor of human MMP in the root canal.
  
  
  METHODS
  Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Phendione on E. faecalis were determined. The antimicrobial properties of Phendione in the presence of dentin powder and various transition metal ions were examined. The ability of Phendione to inhibit human MMP-2 was subsequently tested. The efficacy of Phendione against E. faecalis biofilm was determined by exposure of 7-day-old E. faecalis biofilms to Phendione.
  
  
  RESULTS
  The MIC and MBC of Phendione were 2.0 μg/mL and 16 μg/mL, respectively, whereas 64 μg/mL was required to kill E. faecalis biofilm. Phendione completely eradicated E. faecalis despite dentin preincubation. The presence of Zn(2+), and to a lesser extent Fe(2+), abrogated the antimicrobial effect of Phendione. In addition, Phendione at MIC and MBC significantly inhibited human MMP-2 activity.
  
  
  CONCLUSIONS
  Phendione effectively eradicated E. faecalis biofilms and significantly inhibited human MMP-2 through its ability to chelate metal ions. The antibacterial property of Phendione was preserved in the presence of dentin. Phendione can potentially be applied in endodontic treatment as both an antimicrobial agent and MMP inhibitor.
authors: Faculty of Dentistry, National University of Singapore, Singapore.
authors: Chiew Xsia
authors: CX
authors: Tay
authors: Faculty of Dentistry, National University of Singapore, Singapore.
authors: Samantha Yiling
authors: SY
authors: Quah
authors: National Dental Center, Singapore.
authors: Jeen Nee
authors: JN
authors: Lui
authors: Faculty of Dentistry, National University of Singapore, Singapore.
authors: Victoria Soo Hoon
authors: VS
authors: Yu
authors: Faculty of Dentistry, National University of Singapore, Singapore. Electronic address: denkst@nus.edu.sg.
authors: Kai Soo
authors: KS
authors: Tan
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D003786:Dental Pulp Cavity / Q000382:microbiology*; D013293:Enterococcus faecalis / Q000187:drug effects*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D010485:Periapical Periodontitis / Q000382:microbiology; D010618:Phenanthrolines / Q000494:pharmacology*; D014131:Trace Elements / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D002614:Chelating Agents; D061965:Matrix Metalloproteinase Inhibitors; D010618:Phenanthrolines; D014131:Trace Elements; C037153:1,10-phenanthroline-5,6-dione; D020778:Matrix Metalloproteinase 2
keywords: Biofilm; Enterococcus faecalis; matrix metalloproteinase inhibitor