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基于全基因组比较分析的泰国鸟分枝杆菌复合群临床分离株的多样性和抗菌药物耐药谱

Diversity and antimicrobial resistance profiles of Mycobacterium avium complex clinical isolates in Thailand based on whole genome comparative analysis.

作者信息

Sawaswong Vorthon, Wongjarit Kanphai, Petsong Suthidee, Yuliani Yonita, Somsukpiroh Ubonwan, Faksri Kiatichai, Forde Taya, Payungporn Sunchai, Rotcheewaphan Suwatchareeporn

机构信息

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.

Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

出版信息

Sci Rep. 2025 Jan 4;15(1):772. doi: 10.1038/s41598-024-84511-z.

Abstract

The Mycobacterium avium complex (MAC) is a group of closely related nontuberculous mycobacteria that can cause various diseases in humans. In this study, genome sequencing, comprehensive genomic analysis, and antimicrobial susceptibility testing of 66 MAC clinical isolates from King Chulalongkorn Memorial Hospital, Bangkok, Thailand were carried out. Whole-genome average nucleotide identity (ANI) revealed the MAC species distribution, comprising 54 (81.8%) M. intracellulare, 6 (9.1%) M. avium, 5 (7.6%) M. colombiense, and 1 (1.5%) M. timonense. Phylogenetic analysis revealed a high diversity of M. intracellulare isolates and their evolutionary relationships which could be divided into 2 subspecies: M. intracellulare subsp. intracellulare and M. intracellulare subsp. chimaera. In addition, M. intracellulare subsp. chimaera mostly clustered in the distinct clades separated from M. intracellulare strains originating from other countries. Most MAC isolates were resistant to linezolid and moxifloxacin based on phenotypic antimicrobial susceptibility testing. Mutations within rrl gene associated with clarithromycin resistance were detected in M. intracellulare and M. colombiense. The pan-genome analysis presented clade-specific proteins for M. intracellulare, such as PE and PPE protein families. This study provides valuable insights into the genomic diversity and antimicrobial resistance profiles of MAC isolates circulating in Thailand, which are useful for clinical management, guiding the development of targeted diagnostic, and treatment strategies for MAC infections.

摘要

鸟分枝杆菌复合体(MAC)是一组密切相关的非结核分枝杆菌,可导致人类多种疾病。在本研究中,对来自泰国曼谷朱拉隆功国王纪念医院的66株MAC临床分离株进行了全基因组测序、综合基因组分析和药敏试验。全基因组平均核苷酸同一性(ANI)揭示了MAC菌种分布,包括54株(81.8%)细胞内分枝杆菌、6株(9.1%)鸟分枝杆菌、5株(7.6%)哥伦比亚分枝杆菌和1株(1.5%)蒂莫内分枝杆菌。系统发育分析揭示了细胞内分枝杆菌分离株的高度多样性及其进化关系,可分为2个亚种:细胞内分枝杆菌亚种细胞内分枝杆菌和细胞内分枝杆菌亚种嵌合体分枝杆菌。此外,嵌合体分枝杆菌亚种大多聚集在与源自其他国家的细胞内分枝杆菌菌株分离的不同进化枝中。根据表型药敏试验,大多数MAC分离株对利奈唑胺和莫西沙星耐药。在细胞内分枝杆菌和哥伦比亚分枝杆菌中检测到与克拉霉素耐药相关的rrl基因突变。泛基因组分析展示了细胞内分枝杆菌的进化枝特异性蛋白,如PE和PPE蛋白家族。本研究为泰国流行的MAC分离株的基因组多样性和耐药谱提供了有价值的见解,有助于临床管理,指导针对MAC感染的靶向诊断和治疗策略的制定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf1b/11700178/54002a4884dc/41598_2024_84511_Fig1_HTML.jpg

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