Yu Zelin, Wang Ruibai
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, National Institute for Communicable Disease Control and Prevention, Chinese Centre for Disease Control and Prevention, Beijing, Beijing, China.
J Clin Microbiol. 2025 Aug 13;63(8):e0069725. doi: 10.1128/jcm.00697-25. Epub 2025 Jul 24.
(Mab) is a clinically significant non-tuberculous mycobacterium. It comprises three distinct subspecies being considered to have different macrolide susceptibilities, transmission patterns, and treatment outcomes. In this study, systematic analysis was conducted on 2,006 Mab genomes deposited in the National Center for Biotechnology Information genome database, and the taxonomic classification of their subspecies was revised accordingly. The findings revealed that: (i) in terms of three distinct subspecies classification, the analysis based on core genes and average nucleotide identity (ANI) values was completely consistent; (ii) ANI was a reliable criterion for Mab species and subspecies classification, with defined thresholds of 95% ANI for species-level and 98% ANI for subspecies-level differentiations; and (iii) the integrity of the (41) gene or the similarity of the gene was an unreliable characteristic for Mab subspecies, and the assertions that subspecies lack inducible resistance to macrolides also cannot be sustained. Moreover, through a subspecies re-classification of genomes and pangenome analysis, Mab subspecies-specific genes were successfully identified, and a novel single-gene test with enhanced clinical applicability was developed. Additionally, the impact of reference genome selection on taxonomic classification highlighted the importance of adopting a standardized set of reference genomes in species/subspecies identification to significantly enhance the comparability across different studies.IMPORTANCE (Mab) is a clinically challenging non-tuberculous mycobacteria species. The accurate identification of subspecies is of utmost importance for clinical diagnosis and treatment, as well as for research on pathogenicity, drug resistance, and other related aspects. This study provided a clear average nucleotide identity threshold for Mab subspecies classification, as well as revised options of the three Mab subspecies, new and accurate Mab subspecies-special biomarker, and a detection technique with practical clinical application.
脓肿分枝杆菌（Mab）是一种具有临床意义的非结核分枝杆菌。它由三个不同的亚种组成，被认为具有不同的大环内酯敏感性、传播模式和治疗结果。在本研究中，对美国国立生物技术信息中心基因组数据库中存储的2006个脓肿分枝杆菌基因组进行了系统分析，并据此对其亚种的分类进行了修订。研究结果显示：（i）在三个不同亚种的分类方面，基于核心基因和平均核苷酸同一性（ANI）值的分析完全一致；（ii）ANI是脓肿分枝杆菌种和亚种分类的可靠标准，物种水平分类的定义阈值为ANI 95%，亚种水平区分的定义阈值为ANI 98%；（iii）（41）基因的完整性或该基因的相似性对于脓肿分枝杆菌亚种来说是不可靠的特征，关于亚种缺乏对大环内酯类药物的诱导抗性这一说法也无法成立。此外，通过对基因组进行亚种重新分类和泛基因组分析，成功鉴定出脓肿分枝杆菌亚种特异性基因，并开发了一种临床适用性更强的新型单基因检测方法。此外，参考基因组选择对分类学分类的影响突出了在物种/亚种鉴定中采用一套标准化参考基因组的重要性，以显著提高不同研究之间的可比性。重要性 脓肿分枝杆菌（Mab）是一种在临床上具有挑战性的非结核分枝杆菌物种。亚种的准确鉴定对于临床诊断和治疗以及致病性、耐药性和其他相关方面的研究至关重要。本研究为脓肿分枝杆菌亚种分类提供了明确的平均核苷酸同一性阈值，以及对三个脓肿分枝杆菌亚种的修订选项、新的和准确的脓肿分枝杆菌亚种特异性生物标志物，以及一种具有实际临床应用价值的检测技术。
