Department of Infectious Diseases, Japan.
Department of Infectious Diseases, Japan; Pathogenic Microbe Laboratory, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
Clin Microbiol Infect. 2015 Mar;21(3):248.e1-8. doi: 10.1016/j.cmi.2014.09.013. Epub 2014 Oct 13.
Sequences of the full genomes of 259 clinical isolates of Mycobacterium tuberculosis, obtained from foreign-born and Japan-born patients in Tokyo, Japan, were determined, and a phylogenetic tree constructed by concatenated single-nucleotide polymorphism (SNP) sequences. The 259 isolates were clustered into four clades: Lineage 2 (East Asian or "Beijing" genotype; n = 182, 70.3%), Lineage 4 (Euro-American, n = 46, 17.8%), Lineage 1 (Indo-Oceanic, n = 23, 8.9%), and Lineage 3 (East African-Indian, n = 8, 3.1%). Of the 259, 36 (13.9%) were resistant to at least one drug. There was no multi-drug-resistant isolate. Drug resistance was greater for the strains in Lineage 2 than the non-Lineage 2. The proportion of Lineage 2 isolates was significantly smaller in foreign-born (n = 43/91, 47.3%) than in Japan-born (n = 139/168, 82.7%) patients, whereas the proportion of Lineage 1 isolates was significantly larger in foreign-born (n = 19/91, 20.9%) than in Japan-born (n = 4/168, 2.4%) patients. We also found eight SNPs specific to the typical Beijing sub-genotype in Lineage 2, including 4 non-synonymous SNPs. Of the 259 isolates, 244 had strain-specific SNP(s) and small (1-30-bp) insertions and deletions (indels). The numbers of strain-specific SNPs and indels per isolate were significantly larger from foreign-born (median 89, range 0-520) than from Japan-born (median 23, range 0-415) (p 3.66E-15) patients. These results suggested that M. tuberculosis isolates from foreign-born patients had more genetic diversity than those from Japan-born patients.
对 259 株来自日本东京的外国出生和日本出生的肺结核患者的结核分枝杆菌全基因组序列进行了测定，并通过串联单核苷酸多态性 (SNP) 序列构建了系统发育树。259 株分离株分为 4 个分支：谱系 2（东亚或“北京”基因型；n = 182，70.3%）、谱系 4（欧美，n = 46，17.8%）、谱系 1（印度-太平洋，n = 23，8.9%）和谱系 3（东非-印度，n = 8，3.1%）。259 株中，有 36 株（13.9%）至少对一种药物耐药。没有耐多药分离株。谱系 2 菌株的耐药性高于非谱系 2 菌株。外国出生患者（n = 43/91，47.3%）的谱系 2 分离株比例明显小于日本出生患者（n = 139/168，82.7%），而外国出生患者（n = 19/91，20.9%）的谱系 1 分离株比例明显大于日本出生患者（n = 4/168，2.4%）。我们还发现了 8 个与谱系 2 中典型北京亚基因型特异性相关的 SNP，包括 4 个非同义 SNP。259 株中，244 株有菌株特异性 SNP(s)和小（1-30bp）插入和缺失（indels）。外国出生患者（中位数 89，范围 0-520）的菌株特异性 SNP 和 indel 数量明显多于日本出生患者（中位数 23，范围 0-415）（p 3.66E-15）。这些结果表明，来自外国出生患者的结核分枝杆菌分离株比来自日本出生患者的分离株具有更多的遗传多样性。
