The oral pathogen Streptococcus mutans communicates using a canonical Gram‐positive quorum sensing system, CSP‐ComDE. The CSP pheromone already known to be involved in the development of genetic competence positively influences the formation of persisters, dormant variants of regular cells that are highly tolerant to antimicrobial therapy. It is now believed that the persistence phenotype is the end result of a stochastic switch in the expression of toxin‐antitoxin (TA) modules. TAs consist of a pair of genes that encode two components, a stable toxin and its cognate labile antitoxin. Transcription analyses revealed that three core genes encoding a putative TA system, called SmuATR, were members of the S. mutans CSP regulon. We hypothesized that S. mutans is using its CSP‐ComDE system as a deterministic mechanism for persister formation through the activation of smuATR locus. We showed here that the SmuATR system constitutes a novel tripartite type II TA system in which the smuA and smuT genes encode an antitoxin and a toxin, respectively, while SmuR is a transcriptional repressor involved in the autoregulation of the operon. Ectopic expression of SmuA – SmuT is associated with the CSP‐inducible persistence phenotype. In contrast, overexpression of SmuT alone is bactericidal and causes membrane permeabilization. To our knowledge, SmuATR is the first functional chromosomal tripartite TA system shown to be induced by the bacterial quorum sensing system and involved in persister formation.

中文翻译：

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群体感应诱导的三方毒素-抗毒素模块与变形链球菌的持久性表型有关。

口腔病原体变形链球菌使用规范的革兰氏阳性定额感应系统CSP-ComDE进行通信。已知已参与遗传能力发展的CSP信息素积极影响持久性细胞的形成，持久性细胞是高度耐受抗菌疗法的常规细胞的休眠变体。现在认为，持久性表型是毒素-抗毒素（TA）模块表达中随机转换的最终结果。TA由一对编码两种成分的基因组成，一种是稳定的毒素，另一种是不稳定的抗毒素。转录分析显示，编码假定的TA系统的三个核心基因称为SmuATR，是变形链球菌CSP调节子的成员。我们假设变形链球菌正在使用其CSP-ComDE系统作为通过激活smuATR基因座形成持久性的确定性机制。我们在这里表明，SmuATR系统构成了一个新型的三方II型TA系统，其中smuA和smuT基因分别编码一种抗毒素和一种毒素，而SmuR是参与操纵子自动调节的转录阻遏物。SmuA – SmuT的异位表达与CSP诱导的持久性表型有关。相反，仅SmuT的过度表达具有杀菌作用，并引起膜通透性。据我们所知，SmuATR是第一个功能性染色体三方TA系统，显示出它是由细菌群体感应系统诱导并参与形成持久性的。