变异链球菌存在多种糖的代谢途径，且不同糖代谢途径产生的致龋毒力因子不同。糖的代谢过程包括胞外代谢、摄入和胞内代谢。研究表明VicRK与CovR信号系统存在相互调节且在蔗糖的胞外多糖合成中起着相反的作用。但它们之间的相互作用机制，相互作用是否影响糖代谢其它过程以及对糖的选择性尚未见报道。申请人通过前期研究，发现vicR/K与covR基因均可影响蔗糖胞内代谢和其它糖的代谢途径，因而创新的提出VicRK与CovR双组份系统在多个层面相互作用，进而调控糖代谢途径选择性与致龋性的假说。课题拟采用各种分子生物学技术结合动物实验：①探讨变异链球菌VicRK与CovR双组份信号系统间的相互作用方式与机制；②明确其相互作用对糖的胞外、摄入以及胞内代谢调控机制；③阐明其相互作用对糖代谢选择性与致龋性的影响。该研究可加深对全面调节因子VicRK以及CovR环境适应性应答机制的理解，为龋病防控提供新的理论依据。

Streptococcus mutans has many kinds of carbohydrates metabolic pathways, and different pathway can produce different cariogenic factors. The metabolism process includes extracellular metabolism, internalization and intracellular metabolism. Studies have shown that VicRK and CovR signal systems are mutually regulated and play opposite roles in extracellular polysaccharide synthesis from sucrose. However, the mechanism of their interaction, whether it affects other processes of carbohydrates metabolism and the selectivity of carbohydrates have not been reported. Through previous studies, the applicant found that both vicR/K and covR genes can affect intracellular metabolism of sucrose and the metabolic pathways of other carbohydrates. Therefore, a novel hypothesis was proposed that VicRK and CovR two-component system interact on multiple levels to regulate cariogenicity and selectivity of carbohydrates metabolism pathways. We intend to use various molecular biology techniques combined with animal experiments: ① to explore the interaction mode and mechanism between the VicRK and CovR two-component signal system of streptococcus mutants;②to determine how their interaction regulates the extracellular, intake and intracellular metabolism;③ to elucidate the effect of their interaction on the selectivity of carbohydrates metabolism and cariogenicity. This project would reveal the adaptive response mechanism of the global regulatory factor VicRK and CovR of streptococcus mutans, and pursue the new valid management for caries prevention and therapy.