Method: One library of small molecular inhibitors was screened based on the antibacterial activity and ability of inhibiting biofilm formation. To find the antibacterial mechanism, transposon libraries of S. mutans were made to screen the insertion mutants that are resistant to the selected inhibitors.
Result: Nineteen small molecular inhibitors in the library have antibacterial activity to S. mutans, none of them specifically inhibits biofilm formation. Interestingly, four of them belong to selective estrogen receptor modulators, and they have potent antibacterial activity. IC50 of one compound against S. mutans is 1.56uM. Two insertion mutants were selected from the transposon library, and the insertions occurs in two genes Smu_546 and Smu_874 genes that supposed to encode the targets of these selective estrogen receptor modulators.
Conclusion: Our study revealed that SERMs inhibit S. mutans. The underlying mechanism of the inhibition is small molecule inhibitors potentially bind to some proteins to inhibit viability of S. mutans.