Comparative genomics and DNA methylation analysis of Pseudomonas aeruginosa clinical isolate PA3 by single-molecule real-time sequencing reveals new targets for antimicrobials.
Comparative genomics and DNA methylation analysis of Pseudomonas aeruginosa clinical isolate PA3 by single-molecule real-time sequencing reveals new targets for antimicrobials.
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DOI：
10.3389/fcimb.2023.1180194
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发表时间：
2023
影响因子：
5.7
通讯作者：
Yang, Zichen
中科院分区：
文献类型：
--
作者：
Li, Zijiao;Zhou, Xiang;Liao, Danxi;Liu, Ruolan;Zhao, Xia;Wang, Jing;Zhong, Qiu;Zeng, Zhuo;Peng, Yizhi;Tan, Yinling;Yang, Zichen
关键词：
铜绿假单胞菌是一种重要的条件致病菌，具有广泛的环境适应性和复杂的耐药性。单分子实时（SMRT）测序技术具有更长的读取长度序列，更准确，并能够识别表观遗传DNA改变。本研究应用SMRT技术对临床分离的铜绿假单胞菌PA 3进行测序，获得其基因组序列和甲基化修饰信息。对PA 3进行了基因组、比较、泛基因组和表观遗传学分析。发现了PA 3的一般基因组注释，以及关于毒力因子、调节蛋白（RP）、分泌蛋白、II型毒素-抗毒素（TA）对和基因组岛的信息。全基因组比较显示，PA 3在同一性方面与其他铜绿假单胞菌菌株相当，但在水平基因转移（HGT）方面有所不同。系统发育分析表明，PA 3与铜绿假单胞菌60503和铜绿假单胞菌8380的亲缘关系较近。铜绿假单胞菌的泛基因组由大约4，300个基因的核心基因组和至少5，500个基因的辅助基因组组成。表观遗传学分析的结果确定了一个主要的甲基化位点，N6-甲基腺苷（m6 A）和1个基序（CATNNNNNNTCCT/AGGANNNNNATG）。挑选出16个有意义的甲基化位点。其中，purH、phaZ和莱克萨A基因在PA 3的耐药性和生物环境适应性中起重要作用，对这些基因的靶向研究将有助于进一步的抗菌研究。本研究提供了铜绿假单胞菌PA 3基因组的详细可视化和DNA甲基化信息，为后续研究DNA甲基转移酶控制铜绿假单胞菌致病性的分子机制奠定了基础。
Pseudomonas aeruginosa (P.aeruginosa) is an important opportunistic pathogen with broad environmental adaptability and complex drug resistance. Single-molecule real-time (SMRT) sequencing technique has longer read-length sequences, more accuracy, and the ability to identify epigenetic DNA alterations. This study applied SMRT technology to sequence a clinical strain P. aeruginosa PA3 to obtain its genome sequence and methylation modification information. Genomic, comparative, pan-genomic, and epigenetic analyses of PA3 were conducted. General genome annotations of PA3 were discovered, as well as information about virulence factors, regulatory proteins (RPs), secreted proteins, type II toxin-antitoxin (TA) pairs, and genomic islands. A genome-wide comparison revealed that PA3 was comparable to other P. aeruginosa strains in terms of identity, but varied in areas of horizontal gene transfer (HGT). Phylogenetic analysis showed that PA3 was closely related to P. aeruginosa 60503 and P. aeruginosa 8380. P. aeruginosa's pan-genome consists of a core genome of roughly 4,300 genes and an accessory genome of at least 5,500 genes. The results of the epigenetic analysis identified one main methylation sites, N6-methyladenosine (m6A) and 1 motif (CATNNNNNNNTCCT/AGGANNNNNNNATG). 16 meaningful methylated sites were picked. Among these, purH, phaZ, and lexA are of great significance playing an important role in the drug resistance and biological environment adaptability of PA3, and the targeting of these genes may benefit further antibacterial studies. This study provided a detailed visualization and DNA methylation information of the PA3 genome and set a foundation for subsequent research into the molecular mechanism of DNA methyltransferase-controlled P. aeruginosa pathogenicity.
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影响因子：
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作者：
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Zhang, Liqing
DOI：
10.1146/annurev-pathmechdis-012418-012751
发表时间：
2019-01-24
期刊：
Annual review of pathology
影响因子：
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作者：
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通讯作者：
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作者：
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