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To investigate the mechanism of Triton X-100 (TX-100) reducing the Ag + -resistance of Enterococcus faecalis (E. faecalis), and evaluate the antibacterial effect of TX-100 + Ag + against the induced Ag + -resistant E. faecalis (AREf). The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of AgNO 3 against E. faecalis with/without TX-100 were determined to verify the enhanced antibacterial activity. Transmission electron microscopy (TEM) was used to observe the morphological changes of E. faecalis after treatment. The intra- and extracellular concentration of Ag + in treated E. faecalis was evaluated using inductively coupled plasma mass spectrometer (ICP-MS). The changes in cell membrane potential and integrity of treated E. faecalis were also observed using the flow cytometer. Moreover, AREf was induced through continuous exposure to sub-MIC of Ag + and the antibacterial effect of TX-100 + Ag + on AREf was further evaluated. The addition of 0.04% TX-100 showed maximal enhanced antibacterial effect of Ag + against E. faecalis. The TEM and ICP-MS results demonstrated that TX-100 could facilitate Ag + to enter E. faecalis through changing the membrane structure and integrity. Flow cytometry further showed the effect of TX-100 on membrane potential and permeability of E. faecalis. In addition, the enhanced antibacterial effect of TX-100 + Ag + was also confirmed on induced AREf. TX-100 can facilitate Ag + to enter E. faecalis through disrupting the membrane structure and changing the membrane potential and permeability, thus reducing the Ag + -resistance of E. faecalis and enhancing the antibacterial effect against either normal E. faecalis or induced AREf., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Enterococcus faecalis (E. faecalis) is commonly considered to be one of chief culprits of secondary and persistent root canal infections. As antibiotic resistance has become a global issue, in order to reduce the use of antibiotics, metal ions have recently been widely used as an alternative. Silver ions (Ag + ) have been proved to be a strong bactericide but with high cytotoxicity and discoloration property. Triton X-100 (TX-100) and Ag + were co-used for the first time as a clinical intracanal medication to obtain both enhanced antibacterial effect and low cytotoxicity. The synergistic antibacterial effect of TX-100 + Ag + was tested on both planktonic and biofilm-resident E. faecalis on dentine. And the cytotoxicity was tested on MC3T3-E1 cells. Results confirmed the antibacterial activity against both planktonic and biofilm-resident E. faecalis was dramatically improved after TX-100 incorporation. TX-100 and Ag + mixture demonstrated a similar inhibitory effect as the 2% chlorhexidine (CHX), while the cytotoxicity was much lower than 2% CHX (p < 0.05). In conclusion, TX-100 + Ag + mixture might be developed into a new effective intracanal medication as the 2% CHX., (© 2021. Sociedade Brasileira de Microbiologia.)

Enterococcus faecalis is the main cause of refractory root canal infections in human teeth. The control of root canal infection is one of the conditions necessary for the successful treatment of refractory root canal infections. In the present study, nano-scale silver-zinc-calcium-silica particles loaded with different ratios of silver-zinc were successfully prepared (Ag0.5Zn3-MCSNs and Ag0.5Zn10-MCSNs). The release profiles, antibacterial activity against E. faecalis, infiltration depth into dentinal tubules, biocompatibility and effects on dentin microhardness in vitro were investigated. In addition, the antimicrobial effects of the particles against Enterococcus faecalis reinfection were evaluated in vivo in the teeth of beagle dogs. Ag, Zn, Ca and Si were released from Ag-Zn-MCSNs, and the atomic ratio of silver and zinc released can reach the optimal value of 1 : 12 (Ag0.5Zn10-MCSNs). The particles also showed good biocompatibility and antibacterial activity against Enterococcus faecalis and did not reduce the hardness of dentin. The nanoparticles could be driven into the dentinal tubules of dentin slices by ultrasonic activation. In the root canals of beagle dogs, both Ag0.5Zn3-MCSNs and Ag0.5Zn10-MCSNs demonstrated strong preventive effects against E. faecalis infection. The Ag-Zn-Ca-Si mesoporous nanoparticles may develop into a new effective root canal disinfectant or root canal sealer.

Enterococcus faecalis is a Gram-positive facultative anaerobe involved in many fatal or refractory infections of humans. Silver, often used as silver ions (Ag + ) or nanoparticles (AgNPs), is a strong and broad-spectrum antibacterial agent, but E. faecalis shows resistance against it. Despite this, the knowledge about the resistance of E. faecalis against silver is still lacking. In this study, the silver-resistant E. faecalis strains (AgR and ANR E. faecalis) were established through a serial selection method. Their biological and silver-resistant features as well as the Gene Ontology (GO) in comparison with the original E. faecalis were evaluated. The results showed that the silver-resistant E. faecalis could proliferate as original bacteria and had strong resistance against both Ag + and AgNPs. The minimum bactericidal concentrations (MBCs) of AgNO 3 on original, AgR, and ANR E. faecalis were 400 mg/L, 600 mg/L, and 500 mg/L, and the MBCs of AgNPs on these strains were 80 mg/L, 110 mg/L, and 130 mg/L, respectively. GO analysis revealed significant difference (P < 0.05) in gene expressions of biological process (BP), cellular component (CC), and molecular function (MF) among original, AgR, and ANR E. faecalis. These findings provided a significant basis for further understanding and managing the silver-resistance of E. faecalis in infection-control environments. The mechanism behind Ag + /AgNPs resistance of E. faecalis needs to be further investigated.

Enterococcus faecalis (E. faecalis) is a Gram-positive bacterium closely related to many refractory infections of human and shows the resistant ability against the antibacterial effects of silver. Simvastatin is a semisynthetic compound derived from lovastatin and a hydroxymethyl glutaryl coenzyme A(HMG-COA) reductase inhibitor showing certain inhibitive effects on bacteria. The main purpose of this study was to establish and characterize the Ag + /silver nanoparticles (AgNPs)-resistant E. faecalis, and further evaluate the function of extracellular polymeric substances (EPS) in the silver resistance and the effect of simvastatin on the silver-resistance of E. faecalis. The results showed that the established silver-resistant E. faecalis had strong resistance against both Ag + and AgNPs and simvastatin could decrease the silver-resistance of both original and Ag + /AgNPs-resistant E. faecalis. The Transmission electron microscopy (TEM), High-angle annular dark-field (HAADF) and mapping images showed that the silver ions or particles aggregated and confined in the EPS on surface areas of the cell membrane when the silver-resistant E. faecalis were incubated with Ag + or AgNPs. When the simvastatin was added, the silver element was not confined in the EPS and entered the bacteria. These findings may indicate that the silver resistance of E. faecalis was derived from the entrapping function of EPS, but simvastatin could compromise the function of EPS to decrease the silver resistant ability of E. faecalis.

Enterococcus faecalis (E. faecalis) is one of the dominant bacteria for refractory infections of teeth. Silver ions (Ag+) have been proved to be a strong bactericide but with high cytotoxicity and discoloration property. Simvastatin is an agent used for dyslipidemia treatment and has anti-inflammatory property. In this study, Ag+ and simvastatin were for the first time used in combination, and poly (lactide-co-glycolide) (PLGA) submicron particles carrying both Ag+ and simvastatin (AgS-PLGA) were fabricated for further investigations. Results confirmed the enhanced antibacterial activity against E. faecalis of Ag+ by simvastatin. AgS-PLGA could release both Ag+ and simvastatin for 24 days and also showed enhanced antibacterial activities. On dentin slices, AgS-PLGA could enter dentinal tubules by ultrasonic activation and inhibit the colonization of E. faecalis. AgS-PLGA showed no cytotoxicity on MC3T3-E1 cells and slight suppressive effect on RAW-264.7 cells, and could reduce the secretion of IL-6 and IL-1β of RAW-264.7 cells. AgS-PLGA could be developed as a new biomaterial for infection and inflammation control for dental and related medical treatments. [ABSTRACT FROM AUTHOR]

Mesoporous calcium-silicate nanoparticles (MCSNs) are excellent biomaterials for controlled drug delivery and mineralization induction. In this study, MCSNs were loaded with low-dose silver ion (Ag+) and Triton X-100 (TX-100) as the M-AgTX to achieve both enhanced antibacterial properties and low cytotoxicity for dentin disinfection. The physicochemical property, biocompatibility, infiltration ability into dentinal tubules, anti-bacterial ability against both planktonic Enterococcusfaecalis (E. faecalis) and its biofilm on dentin, effects on dentin microhardness and in vitro mineralization property were systematically investigated. Results confirmed that the MCSNs and M-AgTX nanoparticles showed typical morphology of mesoporous materials and exhibited sustained release of chemicals with an alkaline pH value over time. M-AgTX also exhibited excellent biocompatibility on MC3T3-E1 cells and could eliminate 100% planktonic E. faecalis after 48-h treatment. On dentin slices, it could enter dentinal tubules by ultrasonic activation and inhibit the growth of E. faecalis on dentin. M-AgTX could completely inactive 28-day E. faecalis biofilm. TEM confirmed the destruction of cell membrane integrity and Ag+ infiltration into bacteria by M-AgTX. Besides, dentin slices medicated with M-AgTX nanoparticles displayed an increased microhardness. After being immersed in SBF for 7 days, apatite crystals could be observed on the surface of the material tablets. M-AgTX could be developed into a new multifunctional intra-canal medication or bone defect filling material for infected bone defects due to its sustained release profile, low cytotoxicity, infiltration ability, enhanced anti-bacterial and mineralization features. [ABSTRACT FROM AUTHOR]