DNA adenine methylation is involved in persister formation in E. coli
DNA adenine methylation is involved in persister formation in E. coli
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DNA 腺嘌呤甲基化参与大肠杆菌中持续细胞的形成
DOI：
10.1016/j.micres.2021.126709
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发表时间：
2021
影响因子：
6.7
通讯作者：
Zhang Wenhong
中科院分区：
文献类型：
--
作者：
Xu Yuanyuan;Liu Shuang;Zhang Ying;Zhang Wenhong
尿路致病性大肠杆菌（UPEC）是引起尿路感染的主要病原体。UPEC耐药菌在临床治疗失败和复发中起着至关重要的作用。虽然已知DNA甲基化可调节基因表达，但其在持续性形成中的作用尚未研究。在此，我们发现来自UPEC菌株UTI89的Δdam（腺嘌呤甲基化酶）突变体在持久酶形成方面存在显著缺陷，并且Δ dam突变体的互补恢复了这一缺陷。利用PacBio的甲基化组测序和Δdam的RNA测序，我们首次定义了Dam在持续性形成中的作用。我们发现Δdammutation对基因组的去甲基化具有压倒性的影响，并且去甲基化位点影响参与广泛转录和代谢过程的基因的表达。使用甲基化组和转录组的比较COG分析，我们表明，大坝介导的持续形成通过转录控制，细胞运动，DNA修复和代谢物运输过程。这些发现提供了DNA甲基化介导的耐药菌形成的第一个证据和分子基础，并暗示Dam DNA甲基化是耐药菌的潜在药物靶点。
UropathogenicEscherichia coli(UPEC) is a major cause of urinary tract infections (UTI). UPEC persister bacteria play crucial roles in clinical treatment failure and relapse. Although DNA methylation is known to regulate gene expression, its role in persister formation has not been investigated. Here, we show that Δdam(adenine methylase) mutant from UPEC strain UTI89 had significant defect in persister formation and complementation of the Δdammutant restored this defect. Using PacBio sequencing of methylome and RNA sequencing of Δdam, we defined, for the first time, the role of Dam in persister formation. We found that Δdammutation had an overwhelming effect on demethylation of the genome and the demethylation sites affected expression of genes involved in broad transcriptional and metabolic processes. Using comparative COG analysis of methylome and transcriptome, we demonstrate that Dam mediates persister formation through transcriptional control, cell motility, DNA repair and metabolite transport processes. These findings provide the first evidence and molecular basis for DNA methylation mediated persister formation and implicate Dam DNA methylation as a potential drug target for persister bacteria.