Inhibition of indole production increases the activity of quinolone antibiotics against E. coli persisters.
Inhibition of indole production increases the activity of quinolone antibiotics against E. coli persisters.
复制标题
抑制吲哚的产生会增加喹诺酮类抗生素对大肠杆菌持续存在的活性。
DOI：
10.1038/s41598-020-68693-w
复制
发表时间：
2020
影响因子：
4.6
通讯作者：
Zarkan A
中科院分区：
文献类型：
--
作者：
Zarkan A
持久性细菌是一种基因敏感的细菌，它们通过进入休眠状态而在抗生素治疗中存活下来。停用抗生素后，从休眠状态出现的顽固分子导致复发性感染。吲哚是一种具有多种信号作用的芳香分子，包括在持久性形成中的作用。在这里，我们证明吲哚刺激形成大肠杆菌对抗喹诺酮类抗生素，靶向DNA回转酶的GyrA亚基。然而，吲哚对e的形成没有影响。对抗氨基香豆素，新生物素，靶向DNA旋切酶的GyrB亚基。吲哚信号传导的两种模式已被描述：持续和脉冲。后者是指在固定相进入时细胞内吲哚短暂而强烈的升高。我们表明，喹诺酮类药物的刺激是由于吲哚脉冲，而不是持久的信号。吲哚在DNA gyrase上的硅对接预测了吲哚与GyrB亚基的ATP结合位点的完美对接。我们认为，抑制吲哚的产生为增强喹诺酮类药物抗ste的活性提供了一条潜在的途径。colipersisters。
Persisters are a sub-population of genetically sensitive bacteria that survive antibiotic treatment by entering a dormant state. The emergence of persisters from dormancy after antibiotic withdrawal leads to recurrent infection. Indole is an aromatic molecule with diverse signalling roles, including a role in persister formation. Here we demonstrate that indole stimulates the formation ofEscherichia colipersisters against quinolone antibiotics which target the GyrA subunit of DNA gyrase. However, indole has no effect on the formation ofE. colipersisters against an aminocoumarin, novobiocin, which targets the GyrB subunit of DNA gyrase. Two modes of indole signalling have been described: persistent and pulse. The latter refers to the brief but intense elevation of intracellular indole during stationary phase entry. We show that the stimulation of quinolone persisters is due to indole pulse, rather than persistent, signalling. In silico docking of indole on DNA gyrase predicts that indole docks perfectly to the ATP binding site of the GyrB subunit. We propose that the inhibition of indole production offers a potential route to enhance the activity of quinolones againstE. colipersisters.