Synergistic mechanism of Ag+-Zn2+ in anti-bacterial activity against Enterococcus faecalis and its application against dentin infection

Background: Ag+ and Zn2+ have already been used in combinations to obtain both enhanced antibacterial effect and low cytotoxicity. Despite this, it is still unclear how the Zn2+ co-works with Ag+ in the synergistic antibacterial activity. The main purposes of this study were to investigate the co-work pattern and optimum ratio between Ag+ and Zn2+ in their synergistic antibacterial activity against E. faecalis, the possible mechanisms behind this synergy and the primary application of optimum Ag+-Zn2+ co-work pattern against the E. faecalis biofilm on dentin. A serial of Ag+-Zn2+ atomic combination ratios were tested on both planktonic and biofilm-resident E. faecalis on dentin, their antibacterial efficiency was calculated and optimum ratio determined. And the cytotoxicity of various Ag+-Zn2+ atomic ratios was tested on MC3T3-E1 Cells. The role of Zn2+ in Ag+-Zn2+ co-work was evaluated using a Zn2+ pretreatment study and membrane potential-permeability measurement. Results: The results showed that the synergistically promoted antibacterial effect of Ag+-Zn2+ combinations was Zn2+ amount-dependent with the 1:9 and 1:12 Ag+-Zn2+ atomic ratios showing the most powerful ability against both planktonic and biofilm-resident E. faecalis. This co-work could likely be attributed to the depolarization of E. faecalis cell membrane by the addition of Zn2+. The cytotoxicity of the Ag+-Zn2+ atomic ratios of 1:9 and 1:12 was much lower than 2% chlorhexidine. Conclusions: The Ag+-Zn2+ atomic ratios of 1: 9 and 1: 12 demonstrated similar strong ability against E. faecalis biofilm on dentin but much lower cytotoxicity than 2% chlorhexidine. New medications containing optimum Ag+-Zn(2+)atomic ratios higher than 1:6, such as 1:9 or 1:12, could be developed against E. faecalis infection in root canals of teeth or any other parts of human body.