摘要

乌克兰位居全球前20位耐多药（MDR）和广泛耐药（XDR）结核分枝杆菌（MTB）病例数最高的国家之列。然而，关于遗传多样性的知之甚少，即来自该地区的临床分离株的抗性标记。我们分析了来自地理上多样的乌克兰州及其南部克里米亚半岛的临床分离株（N = 75）中7种最流行的MDR / XDR抗生素抗性赋予基因。基因组分析显示6例（8％）敏感，3例（4％）对至少一种抗生素耐药，40例（53％）为耐多药，26例（35％）为XDR。大部分分离株（81％）都属于北京的血统。这是第一个使用来自乌克兰的临床分离株的NGS来鉴定赋予MTB耐药性的基因突变的研究。几个分离株具有在其他高负担结核病国家尚未观察到的耐药特征。最值得注意的是，inhA基因启动子突变的缺失，rpoB决定区的多样性突变类型以及异源性的检测提供了来自世界这个地区的MDR / XDR的更广泛的理解。

The Ukraine ranks among the top twenty countries with the highest number of multi-drug resistant (MDR), and extensively drugresistant (XDR) Mycobacterium tuberculosis (MTB) cases in the world. However, little is known of the genetic diversity, i.e.,resistance signatures in clinical isolates from this region. We analyzed seven of most prevalent MDR/XDR antibiotic resistanceconferring genes from clinical isolates (N = 75) collected from geographically diverse Ukrainian oblasts and its southern Crimean peninsula. Genomic analysis revealed 6 (8 %) were sensitive, 3 (4 %) were resistant to at least one antibiotic, 40 (53 %) were MDR, and 26 (35 %) were XDR. The majority of isolates (81 %) were of the Beijing-like lineage. This is the first study to use NGS of clinical isolates from the Ukraine to characterize mutations in genes conferring MTB drug resistance. Several isolates harbored drug resistance signatures that have not been observed in other high burden TB countries. Most notably, the absence of inhA gene promoter mutations, a diversity of mutation types in the rpoB determining region, and detection of heteroresistance provide a broader understanding of MDR/XDR from this area of the world.

https://www.ncbi.nlm.nih.gov/pubmed/29563202