致龋菌形成牙菌斑生物膜是龋病发生的始动因素，目前尚无理想抑制牙菌斑生物膜形成的制剂。变异链球菌（变链菌）是公认致龋菌，近年发现变链菌表面Pac蛋白C123段可折叠成淀粉样纤维，促进生物膜形成，提示C123可成为抑制变链菌生物膜的新靶标。我们前期筛选出3条C123序列中可聚合成淀粉样纤维的六肽，发现它们抑制变链菌生物膜形成且不抗菌，淀粉样六肽处理的变链菌周围出现刚性淀粉样纤维，未见变链菌自身淀粉样纤维。我们推测淀粉样六肽竞争性结合Pac蛋白C123段后聚合成刚性淀粉样纤维包裹变链菌，阻止变链菌自身淀粉样纤维生成，发挥抑制生物膜形成作用。本项目拟进一步阐明淀粉样六肽基本特性、成药性及聚合影响因素，明确淀粉样六肽如何结合C123段抑制变链菌自身淀粉样纤维形成，刚性淀粉样纤维如何阻止变链菌粘附，进而建立致龋模型明确防龋效果。本项目可为开发靶向抑制变链菌生物膜且无广谱抗菌作用的防龋制剂提供依据。

Dental plaque biofilm formation by cariogenic bacteria is the initial factor for dental caries, but there are no ideal anti-biofilm agents up to now. Streptococcus mutans (S.mutans) is a well recognized cariogenic bacterium. Recently, the C123 segment of Pac protein on S.mutans membrane is found to fold into amyloid fiber, and amyloid fibers play important role in S.mutans biofilm formation, which reminds us that preventing C123 folding into amyloid fibers might be a new method to inhibit S.mutans biofilm formation. We previously found that three amyloid hexapeptides derived from C123 were effective in inhibiting S.mutans biofilm formation, without antibacterial effect. The amyloid hexapeptides not only inhibited the formation of S.mutans amyloid fibers, but also formed a mass of rigid amyloid fibers to entangle S.mutans. We hypothesize that these amyloid hexapeptides might competitively bind to the C123 segment of Pac, preventing C123 monomers folding into amyloid fibers, after that the amyloid hexapeptides polymerize into rigid amyloid fibers to entangle S.mutans, preventing S.mutans biofilm formation. On the basis of our previous findings, this project aims to clarify the characteristics and chemopotency of these amyloid hexapeptides, and investigate factors affecting amyloid hexapeptides folding. Further, we explore how amyloid hexapeptides competitively bind to the C123 segment of Pac, and how rigid amyloid fibers inhibit S.mutans biofilm formation. Moreover, the rat cariogenic model will be established to determine whether amyloid hexapeptides could inhibit S.mutans biofilms formation on dental surfaces and their anti-cariogenic effect. This project can provide theoretical basis for the development of new anti-caries drugs targeting at S.mutans biofilm.