Streptococcus mutans (S. mutans) are cariogenic microorganisms. Sortase A (SrtA) is a transpeptidase that attaches Pac to the cell surface. The biofilm formation of S. mutans is promoted by SrtA regulated Pac. Myricetin (Myr) has a variety of pharmacological properties, including inhibiting SrtA activity of Staphylococcus aureus. The purpose of this research was to investigate the inhibitory effect of Myr on SrtA of S. mutans and its subsequent influence on the biofilm formation. Here, Myr was discovered as a potent inhibitor of S. mutans SrtA, with an IC₅₀ of 48.66 ± 1.48 μM, which was lower than the minimum inhibitory concentration (MIC) of 512 ug/mL. Additionally, immunoblot and biofilm assays demonstrated that Myr at a sub-MIC level could reduce adhesion and biofilm formation of S. mutans. The reduction of biofilm was possibly caused by the decreased amount of Pac on the cells’ surface by releasing Pac into the medium via inhibiting SrtA activity. Molecular dynamics simulations and mutagenesis assays suggested that Met123, Ile191, and Arg213 of SrtA were pivotal for the interaction of SrtA and Myr. Our findings indicate that Myr is a promising candidate for the control of dental caries by modulating Pac-involved adhesive mechanisms without developing drug resistance to S.mutans.

变形链球菌（变形链球菌）是致龋微生物。分选酶A（SrtA）是一种将Pac附着到细胞表面的转肽酶。SrtA调控的Pac促进变形链球菌的生物膜形成。杨梅素（Myretin）具有多种药理特性，包括抑制金黄色葡萄球菌的SrtA活性。本研究的目的是研究Myr对变形链球菌SrtA的抑制作用及其对生物膜形成的影响。在这里，发现Myr是变形链球菌SrtA的有效抑制剂，其IC _50为为48.66±1.48μM，低于最低抑制浓度（MIC）512 ug / mL。另外，免疫印迹和生物膜测定法表明，亚MIC水平的Myr可以减少变形链球菌的粘附和生物膜形成。生物膜的减少可能是由于通过抑制SrtA活性将Pac释放到培养基中而导致细胞表面Pac数量减少所致。分子动力学模拟和诱变测定表明，SrtA的Met123，Ile191和Arg213是SrtA和Myr相互作用的关键。我们的发现表明Myr是通过控制Pac参与的黏附机制而不发展对变形链球菌的耐药性来控制龋齿的有前途的候选者。