Bacterial dormancy is a valuable strategy to endure unfavourable conditions. The term ‘persister’ has been coined for cells that tolerate antibiotic treatments due to reduced cellular activity. The type I toxin–antitoxin system tisB/istR‐1 is linked to persistence in Escherichia coli, because toxin TisB depolarizes the inner membrane and causes ATP depletion. Transcription of tisB is induced upon activation of the SOS response by DNA‐damaging drugs. However, translation is repressed both by a 5′ structure within the tisB mRNA and by RNA antitoxin IstR‐1. This tight regulation limits TisB production to SOS conditions. Deletion of both regulatory RNA elements produced a ‘high persistence’ mutant, which was previously assumed to depend on stochastic SOS induction and concomitant TisB production. Here, we demonstrate that the mutant generates a subpopulation of growth‐retarded cells during late stationary phase, likely due to SOS‐independent TisB accumulation. Cell sorting experiments revealed that the stationary phase–derived subpopulation contains most of the persister cells. Collectively our data show that deletion of the regulatory RNA elements uncouples the persister formation process from the intended stress situation and enables the formation of TisB‐dependent persisters in an SOS‐independent manner.

中文翻译：

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tisB/istR-1 毒素-抗毒素系统的转录后失调促进大肠杆菌中不依赖 SOS 的持久性形成

细菌休眠是忍受不利条件的宝贵策略。“持久性”一词是指由于细胞活性降低而耐受抗生素治疗的细胞。I 型毒素-抗毒素系统tisB/istR-1与大肠杆菌中的持久性有关，因为毒素 TisB 使内膜去极化并导致 ATP 耗竭。tisB的转录是在 DNA 损伤药物激活 SOS 反应时诱导的。然而，翻译被tisB内的 5' 结构所抑制mRNA 和 RNA 抗毒素 IstR-1。这种严格的规定将 TisB 的生产限制在 SOS 条件下。两个调控 RNA 元件的缺失产生了一个“高持久性”突变体，以前认为它依赖于随机 SOS 诱导和伴随的 TisB 产生。在这里，我们证明了该突变体在稳定期后期产生了一个生长迟缓的细胞亚群，这可能是由于不依赖于 SOS 的 TisB 积累。细胞分选实验表明，稳定期衍生的亚群包含大部分持久细胞。总的来说，我们的数据表明，调控 RNA 元件的缺失使持久性形成过程与预期的压力情况脱钩，并能够以独立于 SOS 的方式形成依赖于 TisB 的持久性。