Comparative genomics and DNA methylation analysis of Pseudomonas aeruginosa clinical isolate PA3 by single-molecule real-time sequencing reveals new targets for antimicrobials

Frontiers in Cellular and Infection Microbiology

Cellular and Infection Microbiology

Qiu Zhong¹  Yinling Tan¹  Xia Zhao¹  Jing Wang¹  Danxi Liao²  Ruolan Liu²  Xiang Zhou³  Zijiao Li³  Zichen Yang⁴  Yizhi Peng⁵  Zhuo Zeng⁵ 

[1] Department of Microbiology, Army Medical University, The Third Military Medical University, Chongqing, China;Department of Plastic and Cosmetic Surgery, Xinqiao Hospital, The Second Affiliated Hospital, Army Medical University, The Third Military Medical University, Chongqing, China;Department of Plastic and Cosmetic Surgery, Xinqiao Hospital, The Second Affiliated Hospital, Army Medical University, The Third Military Medical University, Chongqing, China;Cadet Brigade 4, College of Basic Medicine, Army Medical University, The Third Military Medical University, Chongqing, China;Department of Plastic and Cosmetic Surgery, Xinqiao Hospital, The Second Affiliated Hospital, Army Medical University, The Third Military Medical University, Chongqing, China;Department of Microbiology, Army Medical University, The Third Military Medical University, Chongqing, China;Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, The First Affiliated Hospital, Army Medical University, The Third Military Medical University, Chongqing, China;Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, The First Affiliated Hospital, Army Medical University, The Third Military Medical University, Chongqing, China;

关键词: Pseudomonas aeruginosa;    SMRT;    comparative genome analysis;    DNA methylation analysis;    epigenetics;    antibacterial;   

DOI  :  10.3389/fcimb.2023.1180194

 received in 2023-03-05, accepted in 2023-07-31,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionPseudomonas 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.MethodsThis 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.ResultsGeneral 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.DisucssionThis 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.

【 授权许可】

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Copyright © 2023 Li, Zhou, Liao, Liu, Zhao, Wang, Zhong, Zeng, Peng, Tan and Yang