Understanding the acid resistance mechanism of S.mutans is crucial for preventing dental caries.FtsZ is the core protein for cell division in bacteria that can polymerize into Z-rings and drive cytokinesis.Our previou...Understanding the acid resistance mechanism of S.mutans is crucial for preventing dental caries.FtsZ is the core protein for cell division in bacteria that can polymerize into Z-rings and drive cytokinesis.Our previous study revealed that the FtsZ in S.mutans(SmFtsZ) has higher self-assembly and GTPase activity under acidic stress,which may be responsible for acid resistance and ca riogenesis of S.mutans.However,the functional structure mechanism of SmFtsZ under low pH conditions is still unclear.Here,we further reported the crystal structure of S.mutans FtsZ,revealing a unique lateral interface.Through protein polymerization and GTPase activity assay,we experimentally demonstrated that the mutation of Arg68 on this lateral interface significantly reduced the functional activity of FtsZ in an acidic environment.The phenotype assay and rat caries model further showed that the mutation of Arg68 effectively inhibited the acid resistance of S.mutans and the occurrence and progress of dental caries in vivo.By employing a molecular dynamics simulation analysis,we conclude that the mutation of Arg68 disrupts the conformation change necessary for SmFtsZ polymerization under acidic conditions.Our study proposes a novel mechanism to maintain FtsZ function in bacteria and could be a potential target for antimicrobial drugs to inhibit the growth of S.mutans in acidic environments.展开更多
基金supported by the Beijing Natural Science Foundation:7222220National Natural Science Foundation of China (82001039)+2 种基金Research Foundation of Peking University School and Hospital of Stomatology:PKUSS20230117The Fundamental Research Funds for the Central UniversitiesYoung Elite Scientist Sponsorship Program by CAST (No.2019QNRC001 to Y.L.L)。
文摘Understanding the acid resistance mechanism of S.mutans is crucial for preventing dental caries.FtsZ is the core protein for cell division in bacteria that can polymerize into Z-rings and drive cytokinesis.Our previous study revealed that the FtsZ in S.mutans(SmFtsZ) has higher self-assembly and GTPase activity under acidic stress,which may be responsible for acid resistance and ca riogenesis of S.mutans.However,the functional structure mechanism of SmFtsZ under low pH conditions is still unclear.Here,we further reported the crystal structure of S.mutans FtsZ,revealing a unique lateral interface.Through protein polymerization and GTPase activity assay,we experimentally demonstrated that the mutation of Arg68 on this lateral interface significantly reduced the functional activity of FtsZ in an acidic environment.The phenotype assay and rat caries model further showed that the mutation of Arg68 effectively inhibited the acid resistance of S.mutans and the occurrence and progress of dental caries in vivo.By employing a molecular dynamics simulation analysis,we conclude that the mutation of Arg68 disrupts the conformation change necessary for SmFtsZ polymerization under acidic conditions.Our study proposes a novel mechanism to maintain FtsZ function in bacteria and could be a potential target for antimicrobial drugs to inhibit the growth of S.mutans in acidic environments.
