Clonality and micro-diversity of a nationwide spreading genotype of Mycobacterium tuberculosis in Japan

Takayuki Wada; Tomotada Iwamoto; Aki Tamaru; Junji Seto; Tadayuki Ahiko; Kaori Yamamoto; Atushi Hase; Shinji Maeda; Taro Yamamoto

doi:10.1371/journal.pone.0118495

Clonality and micro-diversity of a nationwide spreading genotype of Mycobacterium tuberculosis in Japan

PLoS One. 2015 Mar 3;10(3):e0118495. doi: 10.1371/journal.pone.0118495. eCollection 2015.

Authors

Takayuki Wada¹, Tomotada Iwamoto², Aki Tamaru³, Junji Seto⁴, Tadayuki Ahiko⁴, Kaori Yamamoto⁵, Atushi Hase⁵, Shinji Maeda⁶, Taro Yamamoto¹

Affiliations

¹ Department of International Health, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
² Department of Microbiology, Kobe Institute of Health, Kobe, Japan.
³ Department of Microbiology, Osaka Prefectural Institute of Public Health, Osaka, Japan.
⁴ Department of Microbiology, Yamagata Prefectural Institute of Public Health, Yamagata, Japan.
⁵ Department of Microbiology, Osaka City Institute of Public Health and Environmental Sciences, Osaka, Japan.
⁶ Department of Mycobacterium Reference and Research, the Research Institute of Tuberculosis, Tokyo, Japan.

Abstract

Mycobacterium tuberculosis transmission routes can be estimated from genotypic analysis of clinical isolates from patients. In Japan, still a middle-incidence country of TB, a unique genotype strain designated as 'M-strain' has been isolated nationwide recently. To ascertain the history of the wide spread of the strain, 10 clinical isolates from different areas were subjected to genome-wide analysis based on deep sequencers. Results show that all isolates possessed common mutations to those of referential strains. The greatest number of accumulated single nucleotide variants (SNVs) from the oldest coalescence was 13 nucleotides, indicating high clonality of these isolates. When an SNV common to the isolates was used as a surrogate marker of the clone, authentic clonal isolates with variation in a reliable subset of variable number of tandem repeat (VNTR) genotyping method can be selected successfully from clinical isolates populations of M. tuberculosis. When the authentic clones can also be assigned to sub-clonal groups by SNVs derived from the genomic comparison, they are classifiable into three sub-clonal groups with a bias of geographical origins. Feedback from genomic analysis of clinical isolates of M. tuberculosis to genotypic markers will be an efficient strategy for the big data in various settings for public health actions against TB.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Clone Cells
Epidemiological Monitoring
Genotype
High-Throughput Nucleotide Sequencing
Humans
Incidence
Japan / epidemiology
Minisatellite Repeats
Molecular Epidemiology
Mutation
Mycobacterium tuberculosis / classification
Mycobacterium tuberculosis / genetics*
Mycobacterium tuberculosis / isolation & purification
Phylogeny
Phylogeography
Polymorphism, Single Nucleotide*
Tuberculosis, Pulmonary / epidemiology*
Tuberculosis, Pulmonary / microbiology

Grants and funding

This work was supported by a grant from the Ministry of Health, Labour and Welfare (Research on Emerging and Re-emerging Infectious Diseases, Health Sciences Research Grants). This work was also supported in part by Grant-in-Aid for Young Scientists (A) (24689034) and (B) (22790585) from JSPS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.