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YkuR functions as a protein deacetylase in Streptococcus mutans
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2024-10-02 , DOI: 10.1073/pnas.2407820121 Qizhao Ma, Jing Li, Shuxing Yu, Jing Zhou, Yaqi Liu, Xinyue Wang, Dingwei Ye, Yumeng Wu, Tao Gong, Qiong Zhang, Lingyun Wang, Jing Zou, Yuqing Li
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2024-10-02 , DOI: 10.1073/pnas.2407820121 Qizhao Ma, Jing Li, Shuxing Yu, Jing Zhou, Yaqi Liu, Xinyue Wang, Dingwei Ye, Yumeng Wu, Tao Gong, Qiong Zhang, Lingyun Wang, Jing Zou, Yuqing Li
Protein acetylation is a common and reversible posttranslational modification tightly governed by protein acetyltransferases and deacetylases crucial for various biological processes in both eukaryotes and prokaryotes. Although recent studies have characterized many acetyltransferases in diverse bacterial species, only a few protein deacetylases have been identified in prokaryotes, perhaps in part due to their limited sequence homology. In this study, we identified YkuR, encoded by smu_318 , as a unique protein deacetylase in Streptococcus mutans . Through protein acetylome analysis, we demonstrated that the deletion of ykuR significantly upregulated protein acetylation levels, affecting key enzymes in translation processes and metabolic pathways, including starch and sucrose metabolism, glycolysis/gluconeogenesis, and biofilm formation. In particular, YkuR modulated extracellular polysaccharide synthesis and biofilm formation through the direct deacetylation of glucosyltransferases (Gtfs) in the presence of NAD + . Intriguingly, YkuR can be acetylated in a nonenzymatic manner, which then negatively regulated its deacetylase activity, suggesting the presence of a self-regulatory mechanism. Moreover, in vivo studies further demonstrated that the deletion of ykuR attenuated the cariogenicity of S. mutans in the rat caries model, substantiating its involvement in the pathogenesis of dental caries. Therefore, our study revealed a unique regulatory mechanism mediated by YkuR through protein deacetylation that regulates the physiology and pathogenicity of S. mutans .
更新日期：2024-10-02
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