Department of Mycobacteriology, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, 3-1-24 Matsuyama, Kiyose, Tokyo, 204-8533, Japan.
Pathogen Genomics Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan.
Sci Rep. 2019 Sep 6;9(1):12823. doi: 10.1038/s41598-019-49219-5.
We investigated the lineages of Mycobacterium tuberculosis (Mtb) isolates from the RYOKEN study in Japan in 2007 and the usefulness of genotypic drug susceptibility testing (DST) using the Genome Research for Asian Tuberculosis (GReAT) database. In total, 667 isolates were classified into lineage 1 (4.6%), lineage 2 (0.8%), lineage 2/Beijing (72.1%), lineage 3 (0.5%), and lineage 4 (22.0%). The nationality, gender, and age groups associated with the isolates assigned to lineage 1 were significantly different from those associated with other lineages. In particular, isolates of lineage 1.2.1 (EAI2) formed sub-clusters and included a 2,316-bp deletion in the genome. The proportion of the isolates resistant to at least one anti-tuberculosis (TB) drug was 10.8%, as determined by either the genotypic or phenotypic method of DST. However, the sensitivities to isoniazid, streptomycin, and ethambutol determined by the genotypic method were low. Thus, unidentified mutations in the genome responsible for drug resistance were explored, revealing previously unreported mutations in the katG, gid, and embB genes. This is the first nationwide report of whole-genome analysis of TB in Japan.
我们调查了 2007 年日本 RYOKEN 研究中结核分枝杆菌（Mtb）分离株的谱系，并评估了利用亚洲结核病基因组研究（GReAT）数据库进行基因耐药性测试（DST）的有效性。总共对 667 株分离株进行了分类，其中谱系 1（4.6%）、谱系 2（0.8%）、谱系 2/北京（72.1%）、谱系 3（0.5%）和谱系 4（22.0%）。与其他谱系相比，与谱系 1 相关的分离株的国籍、性别和年龄组差异显著。特别是，谱系 1.2.1（EAI2）的分离株形成了亚群，并在基因组中包含 2316bp 的缺失。通过基因型或表型 DST 方法确定，至少有 10.8%的分离株对一种以上抗结核（TB）药物具有耐药性。然而，基因型方法确定的异烟肼、链霉素和乙胺丁醇的敏感性较低。因此，探索了导致耐药性的基因组中未识别的突变，发现了 katG、gid 和 embB 基因中以前未报道的突变。这是日本首次对全国范围内的结核病进行全基因组分析。
