Precision Methylome and In Vivo Methylation Kinetics Characterization of Klebsiella pneumoniae.
Precision Methylome and In Vivo Methylation Kinetics Characterization of Klebsiella pneumoniae.
复制标题
肺炎克雷伯菌的精密甲基化和体内甲基化动力学表征
DOI：
10.1016/j.gpb.2021.04.002
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发表时间：
2022-04
影响因子：
9.5
通讯作者：
Zhou, Dongsheng
中科院分区：
文献类型：
--
作者：
Fu, Jing;Zhang, Ju;Yang, Li;Ding, Nan;Yue, Liya;Zhang, Xiangli;Lu, Dandan;Jia, Xinmiao;Li, Cuidan;Guo, Chongye;Yin, Zhe;Jiang, Xiaoyuan;Zhao, Yongliang;Chen, Fei;Zhou, Dongsheng
肺炎克雷伯菌（克雷伯菌）是一种重要的病原体，可引起严重的医院和社区获得性感染。为了系统地研究其甲基化特征，我们测定了14株肺炎克雷伯菌的全基因组序列，包括不同的血清型、多位点序列类型、克隆群、粘度/毒力和耐药性。利用Pacific Biosciences的单分子实时和亚硫酸盐技术进一步表征了它们的甲基组。我们鉴定了15个甲基化基序[13个n6 -甲基腺嘌呤（6mA）和2个5-甲基胞嘧啶（5mC）基序]，其中8个是新的基序。它们对应的DNA甲基转移酶也得到了验证。此外，我们分析了所有菌株共有的GATC和CCWGG甲基化基序的基因组分布，并确定了一些半甲基化/非甲基化的GATC基序的差异分布模式，这些基序往往位于基因间区（IGRs）。具体来说，我们通过模拟复制介导的被动去甲基化和mase催化的再甲基化的动态过程，在全基因组范围内以单碱基分辨率表征了体内甲基化动力学。复制起始区（oriC）和IGRs中GATC基序的缓慢甲基化暗示了复制起始和转录的表观遗传调控。我们的研究结果阐明了首个单碱基分辨率肺炎克雷伯菌的综合动态甲基组图谱，并为更好地理解肺炎克雷伯菌和其他细菌物种的表观遗传调控提供了有用的参考。
Klebsiella pneumoniae (K. pneumoniae) is an important pathogen that can cause severe hospital- and community-acquired infections. To systematically investigate its methylation features, we determined the whole-genome sequences of 14 K. pneumoniae strains covering varying serotypes, multilocus sequence types, clonal groups, viscosity/virulence, and drug resistance. Their methylomes were further characterized using Pacific Biosciences single-molecule real-time and bisulfite technologies. We identified 15 methylation motifs [13 N6-methyladenine (6mA) and two 5-methylcytosine (5mC) motifs], among which eight were novel. Their corresponding DNA methyltransferases were also validated. Additionally, we analyzed the genomic distribution of GATC and CCWGG methylation motifs shared by all strains, and identified differential distribution patterns of some hemi-/un-methylated GATC motifs, which tend to be located within intergenic regions (IGRs). Specifically, we characterized the in vivo methylation kinetics at single-base resolution on a genome-wide scale by simulating the dynamic processes of replication-mediated passive demethylation and MTase-catalyzed re-methylation. The slow methylation of the GATC motifs in the replication origin (oriC) regions and IGRs implicates the epigenetic regulation of replication initiation and transcription. Our findings illustrate the first comprehensive dynamic methylome map of K. pneumoniae at single-base resolution, and provide a useful reference to better understand epigenetic regulation in this and other bacterial species.
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影响因子：
16.8
作者：
Højfeldt JW;Laugesen A;Willumsen BM;Damhofer H;Hedehus L;Tvardovskiy A;Mohammad F;Jensen ON;Helin K
通讯作者：
Helin K
影响因子：
4.4
作者：
de Jong A;Pietersma H;Cordes M;Kuipers OP;Kok J
通讯作者：
Kok J
影响因子：
3.3
作者：
Barel, Itay;Naughton, Brigitte;Brown, Frank L. H.
通讯作者：
Brown, Frank L. H.
影响因子：
4.8
作者：
Coffin, Stephanie R.;Reich, Norbert O.
通讯作者：
Reich, Norbert O.
影响因子：
4.4
作者：
Hargreaves, Katherine R.;Thanki, Anisha M.;Clokie, Martha R. J.
通讯作者：
Clokie, Martha R. J.