Federal Research and Clinical Centre of Physical-Chemical Medicine, Moscow, Russia
Laboratory of Molecular Epidemiology and Evolutionary Genetics, St. Petersburg Pasteur Institute, Saint Petersburg, Russia.
J Clin Microbiol. 2019 Jun 25;57(7). doi: 10.1128/JCM.00215-19. Print 2019 Jul.
The Central Asia outbreak (CAO) clade is a branch of the Beijing genotype that is associated with multidrug resistance, increased transmissibility, and epidemic spread in parts of the former Soviet Union. Furthermore, migration flows bring these strains far beyond their areas of origin. We aimed to find a specific molecular marker of the Beijing CAO clade and develop a simple and affordable method for its detection. Based on the bioinformatics analysis of the large whole-genome sequencing (WGS) data set ( = 1,398), we identified an IS insertion in the intergenic region as a specific molecular marker of the CAO clade. We further designed and optimized a multiplex PCR method to detect this insertion. The method was validated with the recently published WGS data set from Central Asia ( = 277) and experimentally with isolates from European and Asian parts of Russia, the former Soviet Union, and East Asia ( = 319). The developed molecular assay may be recommended for rapid screening of retrospective collections and for prospective surveillance when comprehensive but expensive WGS is not available or practical. The assay may be especially useful in high multidrug-resistant tuberculosis (MDR-TB) burden countries of the former Soviet Union and in countries with respective immigrant communities.
中亚暴发(CAO)分支是与多药耐药性、传染性增加和在前苏联部分地区流行传播相关的北京基因型的一个分支。此外,移民流动将这些菌株带到了远远超出其起源地区的地方。我们旨在寻找北京 CAO 分支的特定分子标记,并开发一种简单且经济实惠的检测方法。基于对大型全基因组测序(WGS)数据集(=1398)的生物信息学分析,我们确定了插入在基因间区的插入序列(IS)是 CAO 分支的特定分子标记。我们进一步设计并优化了一种多重 PCR 方法来检测这种插入。该方法已通过最近公布的中亚 WGS 数据集(=277)进行了验证,并通过来自俄罗斯、前苏联和东亚的欧洲和亚洲部分地区的分离株进行了实验验证(=319)。开发的分子检测方法可用于快速筛选回顾性样本集,以及在无法或不实际进行全面但昂贵的 WGS 时进行前瞻性监测。该检测方法可能特别适用于前苏联高耐多药结核病(MDR-TB)负担国家以及具有相应移民群体的国家。