Please use this identifier to cite or link to this item: https://cris.pasteurorg.ru/handle/123456789/89
Title: Positive epistasis of major low-cost drug resistance mutations rpoB531-TTG and katG315-ACC depends on the phylogenetic background of Mycobacterium tuberculosis strains
Authors: Li, Qin-Jing 
Jiao, Wei-Wei 
Yin, Qing-Qin 
Li, Ying-Jia 
Li, Jie-Qiong 
Xu, Fang 
Sun, Lin 
Xiao, Jing 
Qi, Hui 
Wang, Ting 
Huang, Hai-Rong 
Shen, A-Dong 
Mokrousov, Igor V 
Keywords: Beijing genotype;Clustering;Drug resistance;Epistasis;Mycobacterium tuberculosis;Sublineage
Issue Date: Jun-2017
Publisher: Elsevier
Journal: International Journal of Antimicrobial Agents 
Abstract: Mycobacterium tuberculosis Beijing genotype strains increasingly circulate in different world regions, either as historical endemic, e.g. in East Asia, or recently imported, e.g. in South America, and this family is regarded as the most successful lineage of the global tuberculosis (TB) epidemic. Here we analysed the transmission capacity of these strains in the context of their phylogenetic background and drug resistance mutations. The study collection included all multidrug resistant (MDR) strains of Beijing genotype isolated in Beijing Chest Hospital, the largest tertiary TB facility in North China, in 2011-2013 (n = 278). Strains were subjected to NTF/IS6110 and 24-loci MIRU-VNTR analysis. Drug resistance mutations were detected in rpoB, katG, inhA and oxyR-ahpC. A total of 58 and 220 strains were assigned to the ancient and modern Beijing sublineages, respectively. 24-MIRU-VNTR clustering was higher in modern versus ancient Beijing strains (35.9% vs. 12.1%; P <0.001). After taking into consideration the presence of rpoB and katG mutations, clustering decreased to 15.9% in modern and 0% in ancient strains. The most frequent combination of mutations (rpoB531-TTG and katG315-ACC) was more prevalent in clustered versus non-clustered isolates in the modern sublineage (23/35 vs. 47/185; P <0.0001). To conclude, a combination of the known low-fitness-cost rpoB531-TTG and katG315-ACC mutations likely facilitates the increased transmission ability of MDR strains of the modern but not ancient Beijing sublineage. Accordingly, positive epistasis of major low-cost drug resistance-conferring mutations is influenced by the phylogenetic background of M. tuberculosis strains.
URI: https://cris.pasteurorg.ru/handle/123456789/89
ISSN: 0924-8579
DOI: 10.1016/j.ijantimicag.2017.02.009
Appears in Collections:Cтатьи в журналах/Journal articles

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