The ability of Streptococcus mutans to persist in a variety of adverse environments and to emerge as a numerically dominant member of stable oral biofilm communities are essential elements for its cariogenicity. The S. mutans Cid/Lrg system has been studied as a key player in the integration of complex environmental signals into regulatory networks that modulate virulence and cell homeostasis. Cid/Lrg has also been shown to be closely associated with metabolic pathways of this organism, due to distinct patterns of cid and lrg expression in response to growth phase and glucose/oxygen levels. In this study, a comparison of cid and lrg promoter regions with conserved CodY (a regulator which responds to starvation stress)‐binding motifs revealed the presence of a potential CodY‐binding site, which is arranged similarly in both cid and lrg promoters. Electrophoretic mobility shift assays (EMSAs) and promoter reporter assays demonstrated that expression of the cid and lrg operons is directly mediated by the global transcriptional regulator CodY. DNase I footprinting analyses confirmed the predicted binding sequences for CodY in both the cid and the lrg promoter regions. Overexpression of CodY had no obvious effect on lrgAB expression, but deficiency of CodY still affected lrgAB expression in a lytST‐overexpressing strain, suggesting that CodY is required for the full regulation of lrgAB by LytST. We also demonstrated that both CodY and CcpA are involved in regulating pyruvate flux and utilization. Collectively, these data show that CodY directly regulates cid and lrg expression, and together with CcpA (previously shown to directly regulate cid and lrg promoters) contributes to coordinating pyruvate uptake and utilization in response to both the external environment and the cellular metabolic status.

中文翻译：

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CodY在变形链球菌中对cid和lrg表达的调节。

变形链球菌在各种不利环境中持续存在并作为稳定的口腔生物膜群落的数字优势成员出现的能力是其致龋性的基本要素。将变形链球菌CID /系统Lrg所得已经研究了作为整合复杂的环境信号转换成调控网络调节毒力和细胞稳态的关键角色。由于响应于生长期和葡萄糖/氧气水平的cid和lrg表达的不同模式，Cid / Lrg也已显示与该生物的代谢途径密切相关。在这项研究中，cid和lrg的比较具有保守的CodY（一种响应饥饿压力的调节剂）结合基序的启动子区域揭示了潜在的CodY结合位点的存在，其在cid和lrg启动子中的排列方式相似。电泳迁移率迁移分析（EMSA）和启动子报告基因分析表明，cid和lrg操纵子的表达直接由全局转录调节因子CodY介导。DNase I足迹分析证实了cid和lrg启动子区域中CodY的预测结合序列。CodY的过表达对lrgAB的表达没有明显影响，但是CodY的缺乏仍然影响lrgABlytST过度表达菌株中的表达，表明CodY是LytST完全调节lrgAB所必需的。我们还证明了CodY和CcpA均参与调节丙酮酸通量和利用。总体而言，这些数据表明CodY直接调节cid和lrg的表达，并与CcpA（先前显示直接调节cid和lrg启动子）一起有助于协调丙酮酸的吸收和利用，以响应外部环境和细胞代谢状况。