Toxins Hha and CspD and small RNA regulator Hfq are involved in persister cell formation through MqsR in Escherichia coli.

Toxins Hha and CspD and small RNA regulator Hfq are involved in persister cell formation through MqsR in Escherichia coli.
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DOI:
10.1016/j.bbrc.2009.11.033
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发表时间:
2010-01-01
影响因子:
3.1
通讯作者:
Wood, Thomas K.
Wood, Thomas K.
中科院分区:
生物学4区
文献类型:
--
作者:
Kim, Younghoon;Wood, Thomas K.

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永久性细胞是逃避抗生素等压力的细胞,其特征是新陈代谢减少,缺乏实现这种状态所需的遗传改变。我们先前表明,大肠杆菌的MqsR和MqsA是影响细胞生理学的毒素-抗毒素对(例如,生物膜形成和运动性)。在这里,我们表明,删除mqsRA基因座减少持续性细胞的形成,并与此结果相一致,MqsR的过表达增加持续性细胞的形成。此外,毒素Hha、CspD和HokA增加持续细胞形成。此外,通过在一系列同基因突变体中过量生产MqsR,我们表明Hha和CspD是通过MqsR过表达形成持续细胞所必需的。令人惊讶的是,Hfq,一种小RNA伴侣,降低了持久性。全转录组研究表明,Hfq诱导转运相关基因(opp基因和dppA),外膜蛋白相关基因(ybfM和ybfN),毒素(hha)和蛋白酶(clpX,clpP和lon)。两者合计,这些结果表明,毒素CspD,Hha,和HokA的影响,通过MqsR的持续性细胞的形成和Hfq发挥了重要作用,通过调节运输或外膜蛋白OppA和YbfM的持续性细胞的形成的调节。
Persisters are cells which evade stresses like antibiotics and which are characterized by reduced metabolism and a lack of genetic alterations required to achieve this state. We showed previously that MqsR and MqsA of Escherichia coli are a toxin-antitoxin pair that influence cell physiology (e.g., biofilm formation and motility) via RNase activity as well as through regulation of toxin CspD. Here, we show that deletion of the mqsRA locus decreases persister cell formation and, consistent with this result, overexpression of MqsR increases persister cell formation. Furthermore, toxins Hha, CspD, and HokA increase persister cell formation. In addition, by overproducing MqsR in a series of isogenic mutants, we show that Hha and CspD are necessary for persister cell formation via MqsR overexpression. Surprisingly, Hfq, a small RNA chaperone, decreases persistence. A whole-transcriptome study shows that Hfq induces transport-related genes (opp genes and dppA), outer membrane protein-related genes (ybfM and ybfN), toxins (hha), and proteases (clpX, clpP, and lon). Taken together, these results indicate that toxins CspD, Hha, and HokA influence persister cell formation via MqsR and that Hfq plays an important role in the regulation of persister cell formation via regulation of transport or outer membrane proteins OppA and YbfM.
蛋白质翻译和细胞死亡:稀有TRNA在生物膜形成和激活休眠噬菌体杀手基因中的作用。
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