Multi-clonal evolution of multi-drug-resistant/extensively drug-resistant Mycobacterium tuberculosis in a high-prevalence setting of Papua New Guinea for over three decades
Multi-clonal evolution of multi-drug-resistant/extensively drug-resistant Mycobacterium tuberculosis in a high-prevalence setting of Papua New Guinea for over three decades
复制标题
DOI：
10.1099/mgen.0.000147
复制
发表时间：
2018-02-01
影响因子：
3.9
通讯作者：
Coin, Lachlan
中科院分区：
文献类型：
--
作者：
Bainomugisa, Arnold;Lavu, Evelyn;Coin, Lachlan
据报告，巴布亚新几内亚达鲁岛暴发了耐多药结核病疫情。尚未描述导致此次暴发的结核分枝杆菌菌株和耐药突变的时间累积。2012-2015年期间，从达鲁综合医院转介至布里斯班超国家参考实验室的165株临床分离株中的100株全基因组测序显示，95株属于单一的现代北京亚系菌株。分子年代测定表明，在20世纪60年代获得了链霉素和异烟肼耐药性，并通过mycP 1突变介导了潜在的增强毒力。北京亚系菌株表现出异烟肼和乙硫异烟胺之间的高度共耐药（80/95; 84.2%），归因于inhA启动子突变与inhA和ndh编码突变的组合。在78/95个样本中观察到的多药耐药性是在20世纪80年代随着典型的rpoB突变以及补偿性rpoC突变的获得而出现的。从2009年开始，有氟喹诺酮类和氨基糖苷类耐药的独立获得，以及广泛耐药（XDR）菌株的局部传播证据。这些发现强调了全基因组测序在为有效应对MDR/XDR结核病提供信息方面的重要性。
An outbreak of multi-drug resistant (MDR) tuberculosis (TB) has been reported on Daru Island, Papua New Guinea. Mycobacterium tuberculosis strains driving this outbreak and the temporal accrual of drug resistance mutations have not been described. Whole genome sequencing of 100 of 165 clinical isolates referred from Daru General Hospital to the Supranational reference laboratory, Brisbane, during 2012-2015 revealed that 95 belonged to a single modern Beijing sublineage strain. Molecular dating suggested acquisition of streptomycin and isoniazid resistance in the 1960s, with potentially enhanced virulence mediated by an mycP1 mutation. The Beijing sub-lineage strain demonstrated a high degree of co-resistance between isoniazid and ethionamide (80/95; 84.2 %) attributed to an inhA promoter mutation combined with inhA and ndh coding mutations. Multi-drug resistance, observed in 78/95 samples, emerged with the acquisition of a typical rpoB mutation together with a compensatory rpoC mutation in the 1980s. There was independent acquisition of fluoroquinolone and aminoglycoside resistance, and evidence of local transmission of extensively drug resistant (XDR) strains from 2009. These findings underline the importance of whole genome sequencing in informing an effective public health response to MDR/XDR TB.