Genetic diversity of Mycobacterium tuberculosis isolates from foreign-born and Japan-born residents in Tokyo

Abstract

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.

Whole-genome sequencing-based epidemiological analysis of anti-tuberculosis drug resistance genes in Japan in 2007: Application of the Genome Research for Asian Tuberculosis (GReAT) database

“…Kobayashi et al . reported that in Tokyo, the proportion of lineage 1 isolates was significantly higher in foreign-born patients than in Japanese patients 26 . Therefore, a greater prevalence of lineage 1 isolates would be expected from foreign-born patients.…”

A novel Ancestral Beijing sublineage of Mycobacterium tuberculosis suggests the transition site to Modern Beijing sublineages

“…This hypothesis, together with the high prevalence of L2.1 in Guangxi, conforms to the hypothesis that the origin of the Lineage 2, L2.1 and probably L2.2 or the Beijing strains was in Southern China 7 , where L2.2.2 or the RD181-positive Beijing strains were also highly prevalent 12 . The early L2.2 or Ancestral Beijing strains spread widely from Tibet 13 to Japan 14,15 . In south Eastern Asia they may have diversified by co-evolving with various genetically diverse non-Han Chinese ethnic tribes in the segregated mountainous areas.…”

“…To understand their spreading potential, the geographical origin of L2 or the Beijing strains are sought and debated. A number of studies suggested that they started in Southern China 7,12 and subsequently spread throughout Eastern Asia, from Tibet 13 to Japan 14,15 . The Modern Beijing strains appeared to successfully co-expand with Han Chinese in Northern China 7 .…”

“…It is unclear however whether the Modern Beijing strains originated there or in Southern China, moved with people and subsequently expanded in Northern China 7 . An alternate hypothesis is that the Beijing strains originated in Northern China 16,17 as the Ancestral strains are common in Japan 14,15 and Korea 18 as well as in Jilin province in Northern China 12 .…”

Genetic diversity of Mycobacterium tuberculosis isolates from Tochigi prefecture, a local region of Japan

“…TB isolates from foreign-born patients may increase TB genetic diversity in Tochigi Prefecture. Although no direct evidence has shown that these isolates from foreign-born patients in Tochigi are a risk factor for TB transmission, similar findings were reported for TB isolates from foreign-born and Japan-born TB patients in Tokyo [3]. Of the 13 isolates belonging to Lineage 1, nine were from patients born in other Asian countries, including seven from Southeast Asian countries/regions, where Lineage 1 is predominant [6, 24].…”