Two regulatory RNA elements affect TisB-dependent depolarization and persister formation
Two regulatory RNA elements affect TisB-dependent depolarization and persister formation
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DOI：
10.1111/mmi.13607
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发表时间：
2017-03-01
影响因子：
3.6
通讯作者：
Wagner, E. Gerhart H.
中科院分区：
文献类型：
--
作者：
Berghoff, Bork A.;Hoekzema, Mirthe;Wagner, E. Gerhart H.
细菌的生存策略涉及表型多样性，这种多样性是由调节因子和效应蛋白的噪声表达产生的。细菌如何利用调控RNA在表型之间做出决定的问题是对这些通用调控因子的一般理解的核心。我们研究了大肠杆菌的TISB/ISTR-1毒素-抗毒素系统，以了解RNA抗毒素ISTR-1在TISB依赖的内膜去极化和周围体形成中的作用。持久菌是一种表型变种，通过抑制生长而暂时对药物产生耐受性。RNA抗毒素ISTR-1为DNA损伤条件下依赖TISB的去极化设定了一个阈值，导致了两个亚群：极化和去极化的细胞。此外，我们的数据表明，在DNA损伤较低的情况下，TISB mRNA中的抑制性5 UTR结构作为一个调节RNA元件，延迟TISB的翻译，以避免不适当的去极化。对持久亚群的研究进一步表明，这两个调控RNA元件都影响持久水平和持久时间。这项工作为细菌如何利用调控RNA来控制表型异质性提供了一个有趣的例子。
Bacterial survival strategies involve phenotypic diversity which is generated by regulatory factors and noisy expression of effector proteins. The question of how bacteria exploit regulatory RNAs to make decisions between phenotypes is central to a general understanding of these universal regulators. We investigated the TisB/IstR-1 toxin-antitoxin system of Escherichia coli to appreciate the role of the RNA antitoxin IstR-1 in TisB-dependent depolarization of the inner membrane and persister formation. Persisters are phenotypic variants that have become transiently drug-tolerant by arresting growth. The RNA antitoxin IstR-1 sets a threshold for TisB-dependent depolarization under DNA-damaging conditions, resulting in two sub-populations: polarized and depolarized cells. Furthermore, our data indicate that an inhibitory 5 UTR structure in the tisB mRNA serves as a regulatory RNA element that delays TisB translation to avoid inappropriate depolarization when DNA damage is low. Investigation of the persister sub-population further revealed that both regulatory RNA elements affect persister levels as well as persistence time. This work provides an intriguing example of how bacteria exploit regulatory RNAs to control phenotypic heterogeneity.