Ministry of Education Key Laboratory of Major Diseases in Children, National Key Discipline of Pediatrics (Capital Medical University), National Clinical Research Center for Respiratory Diseases, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
Laboratory of Molecular Epidemiology and Evolutionary Genetics (former Laboratory of Molecular Microbiology), St Petersburg Pasteur Institute, St Petersburg, Russia.
Int J Antimicrob Agents. 2017 Jun;49(6):757-762. doi: 10.1016/j.ijantimicag.2017.02.009. Epub 2017 Apr 26.
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.
结核分枝杆菌北京基因型菌株在不同的世界区域不断传播，无论是作为历史地方性流行的菌株，如在东亚，还是最近输入的菌株，如在南美洲，该家族被认为是全球结核病（TB）流行中最成功的谱系。在这里，我们根据其系统发育背景和药物耐药性突变分析了这些菌株的传播能力。研究集包括 2011 年至 2013 年在北京胸部医院（华北最大的三级结核病医院）分离的所有北京基因型耐多药（MDR）菌株（n=278）。菌株进行了 NTF/IS6110 和 24 位基因 MIRU-VNTR 分析。在 rpoB、katG、inhA 和 oxyR-ahpC 中检测到药物耐药性突变。总共将 58 株和 220 株菌株分配到古代和现代北京亚谱系。现代北京株比古代北京株的 24 位基因 MIRU-VNTR 聚类更高（35.9%比 12.1%；P<0.001）。在考虑到 rpoB 和 katG 突变的存在后，现代菌株的聚类下降到 15.9%，而古代菌株的聚类则下降到 0%。最常见的突变组合（rpoB531-TTG 和 katG315-ACC）在现代亚谱系的聚类与非聚类分离株中更为常见（23/35 比 47/185；P<0.0001）。总之，已知低适应成本 rpoB531-TTG 和 katG315-ACC 突变的组合可能促进了现代北京亚谱系而不是古代北京亚谱系的 MDR 菌株的传播能力增加。因此，主要低费用耐药性赋予突变的正遗传相互作用受结核分枝杆菌菌株的系统发育背景影响。
