Synergistic mechanism of Ag(+)–Zn(2+) in anti-bacterial activity against Enterococcus faecalis and its application against dentin infection

BACKGROUND: Ag(+) and Zn(2+) have already been used in combinations to obtain both enhanced antibacterial effect and low cytotoxicity. Despite this, it is still unclear how the Zn(2+) 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 Zn(2+) in their synergistic antibacterial activity against E. faecalis, the possible mechanisms behind this synergy and the primary application of optimum Ag(+)–Zn(2+) co-work pattern against the E. faecalis biofilm on dentin. A serial of Ag(+)–Zn(2+) 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(+)–Zn(2+) atomic ratios was tested on MC3T3-E1 Cells. The role of Zn(2+) in Ag(+)–Zn(2+)co-work was evaluated using a Zn(2+) pretreatment study and membrane potential—permeability measurement. RESULTS: The results showed that the synergistically promoted antibacterial effect of Ag(+)–Zn(2+) combinations was Zn(2+) amount-dependent with the 1:9 and 1:12 Ag(+)–Zn(2+) 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 Zn(2+). The cytotoxicity of the Ag(+)–Zn(2+) atomic ratios of 1:9 and 1:12 was much lower than 2% chlorhexidine. CONCLUSIONS: The Ag(+)–Zn(2+) 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.