Synergistic In Vitro Antimicrobial Activity of Triton X-100 and Metformin against Enterococcus faecalis in Normal and High-Glucose Conditions

Abstract

The prevention and treatment of oral diseases is more difficult in diabetic patients with poorly controlled blood glucose levels. This study aims to explore an effective, low-cytotoxicity medication for root canal treatment in diabetic patients. The antibacterial effect of the combination of Triton X-100 (TX-100) and metformin (Met) on Enterococcus faecalis (E. faecalis) was evaluated by determining the minimum inhibitory concentration (MIC), minimum bactericidal concentration required to kill 99% bacteria (MBC99) and by conducting dynamic time-killing assays. While the antibiofilm activity was measured by crystal violet (CV) assay, field emission scanning electron microscope (FE-SEM), confocal laser scanning microscope (CLSM) and colony-forming unit (CFU) counting assays. The expression of relative genes was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR), and the cytotoxicity of the new combination on MC3T3-E1 cell was also tested. Results showed that the antibacterial and antibiofilm activities of Met could be significantly enhanced by very low concentrations of TX-100 in both normal and high-glucose conditions, with a much lower cytotoxicity than 2% chlorhexidine (CHX). Thus, the TX-100 + Met combination may be developed as a promising and effective root canal disinfectant for patients with diabetes.

Investigation of the Effectiveness of Metformin and Various Antibiotic Combinations against Pseudomonas aeruginosa Isolates

“…He and ark. [17] investigated synergies between metformin and Triton X-100 in the antibacterial effects of E. faecalis isolates. When metformin and Triton X-100 were combined, they were found to be well below the MIC values detected when used alone.…”

“…Another study investigated the cytotoxic effect of metformin on cells, but no significant cytotoxin effect was observed. Another study, in which the synergy between metformin and Triton X-100 was investigated, investigated the cytotoxicity of metformine, and found no significant cytotoxin in the control group [17]. Another study using Ag+ and metformin on E. faecalis isolates found no significant difference in cell proliferation from the control group to the metformine-treated group [15].…”

“…Patients taking metformin due to diabetes have been shown to have fewer cases of infection [16]. Studies on the combination of metformin and different antibiotics have shown synergies between metformine and antibiotics [13,17].…”

Antibacterial and Immunoregulatory Effects of Metformin against Helicobacter pylori Infection in Rat Model

“…In the present study, the effects of metformin on immune regulation and antibacterial activity were investigated in detail in a rat model of H. pylori infection. Metformin has potential activity against H. pylori, but there is ample evidence of its synergistic effect with conventional antibiotics against Gram-positive and Gram-negative bacteria [5,9,[26][27][28]. Previously, Courtois et al reported that 10 mg/mouse/day of metformin had antibacterial activity 9].…”

Non-Antibiotic Drug Repositioning as an Alternative Antimicrobial Approach

“…In fact, by downregulating the expression of stress genes and CcpA, the combination of TX-100 and metformin hampered the stress response and glycolytic capacity of E. faecalis , thereby decreasing their viability and proliferation and diminishing their pathogenicity and drug resistance. Furthermore, they ascertained the antibiofilm activity of this association against E. faecalis in a dentin biofilm model [ 86 ].…”