变异链球菌是主要的致龋菌。探究肽聚糖合成机制是理解变异链球菌形态变化及其适应、定植过程的关键科学问题。其中肽聚糖合成过程的关键蛋白PBP2x和PBP2b受到骨架蛋白FtsZ的调控，但调控机制不清楚。前期研究中我们报道了变异链球菌骨架蛋白FtsZ“踏车式”的运动行为。我们推测FtsZ的运动行为在对PBP2x和PBP2b的调控中占重要地位，因此本课题拟在此基础上首先利用基因编辑结合电镜光镜技术明确变异链球菌中PBP2x和PBP2b在肽聚糖合成过程中的作用；进一步通过活细胞荧光成像技术分别在细胞水平、亚细胞及单分子水平研究FtsZ对PBP2x和PBP2b的时-空分布以及运动行为的调控作用；最后利用生物化学技术研究FtsZ与PBP2x和PBP2b的体内、外相互作用，明确调控机制。本研究结果将进一步阐明变异链球菌中肽聚糖的合成机制，为深入理解变异链球菌的定植与致病机制以及防龋药物与材料研发奠定基础。

Streptococcus mutans is the major pathogen responsible for caries. Studying the mechanism of peptidoglycan synthesis in one of the vital issues to understand the cell shape variation, adaptive capacity and colonization of Streptococcus mutans. PBP2x / PBP2b, which play key roles in peptidoglycan synthesis, are regulated by FtsZ (cytoskeleton), but the mechanism is still unknown. Our previous study showed that FtsZ exhibits dynamic treadmilling motion in the Streptococcus mutans. According to these results, we hypothesize that FtsZ treadmilling motion might play an important role in regulating the motion of PBP2b / PBP2x. Based on it, firstly, this study will investigate the role of PBP2b and PBP2x in cell shape maintaining and peptidoglycan synthesis in Streptococcus mutans via gene manipulation, electric microscopy and light microscopy. Secondly, by using fluorescence microscopy, we will study how FtsZ and its motion regulate the spatio-temporal localization and motion of PBP2x / PBP2b in cell level, subcellular level and single molecule level, respectively. Lastly, we plan to study the interaction between FtsZ and PBP2x / PBP2b in vivo and in vitro via biochemical methods, revealing the regulatory mechanism. The results will further reveal the mechanism of peptidoglycan synthesis in Streptococcus mutans, providing new insights for the in-depth understanding of colonization and pathogenic mechanism of streptococcus mutans, supporting the anti-caries drugs and biomaterial development.