Strain and lineage-level methylome heterogeneity in the multi-drug resistant pathogenic Escherichia coli ST101 clone
Strain and lineage-level methylome heterogeneity in the multi-drug resistant pathogenic Escherichia coli ST101 clone
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多重耐药致病性大肠杆菌 ST101 克隆的菌株和谱系水平甲基化组异质性
DOI：
10.1101/2020.06.07.138552
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Ashcroft M
中科院分区：
文献类型：
--
作者：
Ashcroft M
大肠杆菌序列型（ST）101是一种新兴的多重耐药谱系，与碳青霉烯耐药相关。我们最近完成了一项关于移动的遗传元件（MGE）及其在ST 101谱系内blaNDM-1传播中的作用的全面基因组学研究。DNA甲基转移酶（MTases）也经常与MGE相关，DNA甲基化指导许多生物过程，包括针对外源DNA的基因组防御和基因表达的调节。Pacific Biosciences单分子真实的时间测序数据的可用性使我们能够在全基因组范围内研究DNA甲基化的作用（甲基化组）。我们定义了两个完整的（MS 6192和MS 6193）和五个草案（MS 6194，MS 6201，MS 6203，MS 6204，MS 6207）ST 101基因组的甲基化组。我们的分析确定了14个推定的MTases和8个N6-甲基腺嘌呤DNA识别位点，其中一个位点以前没有描述过。此外，我们鉴定了在转座子7样转座子内编码的I型MTase，并显示其获得导致两个几乎相同的分离株之间的甲基化组的差异。与13个先前发表的ST 101草案基因组的基因组比较确定了MTase分布的变化，与基因组之间的MGE差异一致，突出了单个E菌株内活性MTase的多样性。共线MGE可以促进E的进化，这是公认的。大肠杆菌由于其毒力和抗性基因库。这项研究强调了移动的遗传元件的潜力，也使高度相似的细菌菌株通过改变甲基化组快速获得全基因组功能差异。coliST 101菌株携带许多移动的遗传元件，其编码毒力决定簇、抗微生物剂抗性和DNA甲基转移酶（MTases）。在这项研究中，我们提供了第一个全面的分析全基因组的DNA甲基化（甲基化组）在七个E。coliST 101基因组。我们鉴定了携带I型限制性修饰系统的转座子，该系统可能导致两个几乎相同的基因组之间的功能差异，并显示了单个基因组区域的小重组事件如何导致整个谱系的全局甲基化组变化。我们还表明，MTase在整个ST 101谱系中的分布与编码它们的移动的遗传元件的存在或不存在一致。本研究显示了单一细菌谱系内MTases的多样性，并显示了菌株和谱系特异性甲基化组如何驱动宿主适应。数据摘要包括读取、组装和基序摘要的序列数据先前已提交给国家生物技术信息中心（https：www.ncbi.nlm.nih.gov），其BioProject Accessions：PRJNA 580334、PRJNA 580336、PRJNA 580337、PRJNA 580338、PRJNA 580339、PRJNA 580341和PRJNA 580340分别用于MS 6192、MS 6193、MS 6194、MS 6201、MS 6203、MS 6204和MS 6207。所有支持性数据、代码、加入和方案已在文章中或通过补充数据文件提供。
Escherichia coliSequence Type (ST)101 is an emerging, multi-drug resistant lineage associated with carbapenem resistance. We recently completed a comprehensive genomics study on mobile genetic elements (MGEs) and their role inblaNDM-1dissemination within the ST101 lineage. DNA methyltransferases (MTases) are also frequently associated with MGEs, with DNA methylation guiding numerous biological processes including genomic defence against foreign DNA and regulation of gene expression. The availability of Pacific Biosciences Single Molecule Real Time Sequencing data for seven ST101 strains enabled us to investigate the role of DNA methylation on a genome-wide scale (methylome). We defined the methylome of two complete (MS6192 and MS6193) and five draft (MS6194, MS6201, MS6203, MS6204, MS6207) ST101 genomes. Our analysis identified 14 putative MTases and eight N6-methyladenine DNA recognition sites, with one site that has not been described previously. Furthermore, we identified a Type I MTase encoded within a Transposon 7-like Transposon and show its acquisition leads to differences in the methylome between two almost identical isolates. Genomic comparisons with 13 previously published ST101 draft genomes identified variations in MTase distribution, consistent with MGE differences between genomes, highlighting the diversity of active MTases within strains of a singleE. colilineage. It is well established that MGEs can contribute to the evolution ofE. colidue to their virulence and resistance gene repertoires. This study emphasises the potential for mobile genetic elements to also enable highly similar bacterial strains to rapidly acquire genome-wide functional differences via changes to the methylome.Impact StatementEscherichia coliST101 is an emerging human pathogen frequently associated with carbapenem resistance.E. coliST101 strains carry numerous mobile genetic elements that encode virulence determinants, antimicrobial resistance, and DNA methyltransferases (MTases). In this study we provide the first comprehensive analysis of the genome-wide complement of DNA methylation (methylome) in sevenE. coliST101 genomes. We identified a Transposon carrying a Type I restriction modification system that may lead to functional differences between two almost identical genomes and showed how small recombination events at a single genomic region can lead to global methylome changes across the lineage. We also showed that the distribution of MTases throughout the ST101 lineage was consistent with the presence or absence of mobile genetic elements on which they are encoded. This study shows the diversity of MTases within a single bacterial lineage and shows how strain and lineage-specific methylomes may drive host adaptation.Data SummarySequence data including reads, assemblies and motif summaries have previously been submitted to the National Center for Biotechnology Information (https://www.ncbi.nlm.nih.gov) under the BioProject Accessions: PRJNA580334, PRJNA580336, PRJNA580337, PRJNA580338, PRJNA580339, PRJNA580341 and PRJNA580340 for MS6192, MS6193, MS6194, MS6201, MS6203, MS6204 and MS6207 respectively. All supporting data, code, accessions, and protocols have been provided within the article or through supplementary data files.
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