Hsp100/Clp ATPase对变异链球菌毒力表达的调控及机制的研究进展

Research progress on the regulation and mechanism of Hsp100/Clp ATPase on virulence expressions in Streptococcus mutans

变异链球菌是龋病的始动因子,依赖其产酸、耐酸及形成生物膜等能力成为了口腔致龋环境中的优势菌。三磷酸腺苷(ATP)依赖的内肽酶Clp(Clp ATPase)属于热休克蛋白100家族(Hsp100)成员,通过调控基因表达和控制关键蛋白的活性影响细菌的多种生物学性能。Hsp100/Clp ATPase中某些成员可结合ATP依赖的丝氨酸蛋白水解酶Clp P形成功能复合体,活化、重组和降解变性蛋白质,维持细菌的蛋白质稳态,辅助细菌抵抗严苛的口腔环境。特异性靶向变异链球菌Hsp100/Clp ATPase有望为龋病防治提供新的思路和方法。本文就Hsp100/Clp ATPase的结构和分类,对变异链球菌基因、蛋白及生物学行为调控,及Hsp100/Clp ATPase靶向药物作用等研究进展进行系统阐述,为进一步分析Hsp100/Clp ATPase与变异链球菌致龋毒力的关系,研发抗龋药物候选靶标奠定基础。

Streptococcus mutans（S.mutans）is the initiating factor of dental caries. Depending on its acid production,acid resistance and biofilm formation ability,S.mutans has been regarded as the predominant bacteria in the oral cariogenic environment. Adenosine triphosphate（ATP） dependent endopeptidase Clp（Clp ATPase）belongs to the heat shock protein 100（heat shock protein,Hsp100）family. It can affect many biological properties of bacteria via regulating gene expression and controlling key proteins activities. Some of Hsp100/Clp ATPase members can bind to the ATP-dependent serine protease Clp P to form functional complexes that have the ability to activate,remodel,and degrade denatured proteins,thus maintaining protein homeostasis and resistance to hostile oral environment.Specifically targeting Hsp100/Clp ATPase of S.mutans is expected to provide new ideas and methods for the prevention and treatment of dental caries. In terms of the structure and classification of Hsp100/Clp ATPase,this review summarizes systematically Hsp100/Clp ATPase related genes,proteins and biological behavior regulations in S.mutans,as well as the roles of drugs that specifically targeted Hsp100/Clp ATPase. A comprehensive foundation of the relationship between Hsp100/Clp ATPase and S.mutans cariogenicity can provide a promising candidate target of anti-caries drugs.