脓肿分枝杆菌复合体(MABC)的成员是耐多药的非结核分枝杆菌,并且越来越多地引起机会性肺部感染。然而,在中国,MABC分离株的遗传分型仍不清楚。对2014年至2016年上海市肺科医院下呼吸道感染患者的69株MABC临床分离株进行基因组分析。收集了69个临床菌株的基因组草案,总长度为4.5至5.6Mb,%GC含量(GC%)范围从63.9%到68.1%,和4,492至5,404个基因每个基因组。药敏试验表明,大多数分离株对许多抗菌药物具有耐药性,包括克拉霉素,但对替加环素敏感.分析显示存在赋予抗生素抗性的基因,包括大环内酯类,氨基糖苷类,利福平,还有四环素.此外,每个基因组鉴定出80至114个毒力基因,包括那些与巨噬细胞入侵有关的,铁掺入,避免免疫清除。移动遗传元件,包括插入序列,转座子,和基因组岛,是在基因组中发现的。所有MABC分离株的系统发育分析与另外41个完整的MABC基因组确定了三个进化枝;46个分离株聚集在进化枝I中,对应于M.脓肿亚科。脓肿,25株属于现有的克隆复合物。总的来说,这是我国首次对MABC临床分离株进行比较基因组分析.这些结果显示了编码抗微生物药物抗性的遗传决定子的显著种内变异,毒力,以及使用当前标记基因组合的移动元素和有争议的亚种分类。这些信息将有助于理解进化,抗菌素耐药性,和MABC菌株的发病机理,并促进未来的疫苗开发和药物设计。重要性在过去的十年里,脓肿分枝杆菌复合体(MABC)分离株感染的报道越来越多。MABC菌株通常在囊性纤维化(CF)患者中显示出高发病率,而在亚洲,这些菌株通常从具有显著基因组多样性的非CF患者中回收.目前的工作涉及抗生素耐药性的分析,毒力,通过全基因组测序,对上海肺科医院非CF肺部患者的69株MABC分离株进行了系统发育分析;它代表了中国首次在基因组水平上对MABC菌株的全面调查。这些发现突出了该组非结核分枝杆菌的多样性,并提供了对进化和发病机理的机制理解。这对于在中国开发针对致命MABC感染的新型有效抗菌疗法具有重要意义。
Members of the Mycobacterium abscessus complex (MABC) are multidrug-resistant nontuberculous mycobacteria and increasingly cause opportunistic pulmonary infections. However, the genetic typing of MABC isolates remains largely unclear in
China. Genomic analyses were conducted for 69 MABC clinical isolates obtained from patients with lower respiratory tract infections in Shanghai Pulmonary Hospital between 2014 and 2016. The draft genomes of the 69 clinical strains were assembled, with a total length of 4.5 to 5.6 Mb, a percent GC content (GC%) ranging from 63.9 to 68.1%, and 4,492 to 5,404 genes per genome. Susceptibility test shows that most isolates are resistant to many antimicrobials, including clarithromycin, but susceptible to tigecycline. Analyses revealed the presence of genes conferring resistance to antibiotics, including macrolides, aminoglycosides, rifampicin, and tetracyclines. Furthermore, 80 to 114 virulence genes were identified per genome, including those related to the invasion of macrophages, iron incorporation, and avoidance of immune clearance. Mobile genetic elements, including insertion sequences, transposons, and genomic islands, were discovered in the genomes. Phylogenetic analyses of all MABC isolates with another 41 complete MABC genomes identified three clades; 46 isolates were clustered in clade I, corresponding to M. abscessus subsp. abscessus, and 25 strains belonged to existing clonal complexes. Overall, this is the first comparative genomic analysis of MABC clinical isolates in
China. These results show significant intraspecies variations in genetic determinants encoding antimicrobial resistance, virulence, and mobile elements and controversial subspecies classification using current marker gene combinations. This information will be useful in understanding the evolution, antimicrobial resistance, and pathogenesis of MABC strains and facilitating future vaccine development and drug design. IMPORTANCE Over the past decade, infections by Mycobacterium abscessus complex (MABC) isolates have been increasingly reported worldwide. MABC strains often show a high incidence in cystic fibrosis (CF) patients, whereas in Asia, these strains are frequently recovered from non-CF patients with significant genomic diversity. The present work involves analyses of the antimicrobial resistance, virulence, and phylogeny of 69 selected MABC isolates from non-CF pulmonary patients in Shanghai Pulmonary Hospital by whole-genome sequencing; it represents the first comprehensive investigation of MABC strains in
China at the genomic level. These findings highlight the diversity of this group of nontuberculous mycobacteria and provide a mechanistic understanding of evolution and pathogenesis, which is valuable for the development of novel and effective antimicrobial therapies for deadly MABC infections in
China.