Abstract
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.
Highlights
Tuberculosis (TB) has been difficult to eradicate, and according to the World Health Organization (WHO) global TB report, there were an estimated 10.4 million new TB infections and 1.3 million deaths worldwide in 2016
Technological developments, such as whole-genome sequencing (WGS) and next-generation sequencing, have enabled the elucidation of the lineages and mutations of drug resistance (DR) genes based on the detection of insertions and deletions in the genome of Mycobacterium tuberculosis (Mtb)[7]
The characteristics of Mtb isolates included in the RYOKEN 2007 nationwide anti-TB drug susceptibility study in Japan and the Genome Research for Asian Tuberculosis (GReAT) database were investigated
Summary
Tuberculosis (TB) has been difficult to eradicate, and according to the World Health Organization (WHO) global TB report, there were an estimated 10.4 million new TB infections and 1.3 million deaths worldwide in 2016 (http://www.who.int/tb/publications/global_report/en/). The number of patients with dual infections of TB and human immunodeficiency virus is high, and multidrug-resistant and extensively drug-resistant forms of TB are emerging in Asian countries[2,3,4,5,6]. Technological developments, such as whole-genome sequencing (WGS) and next-generation sequencing, have enabled the elucidation of the lineages and mutations of drug resistance (DR) genes based on the detection of insertions and deletions in the genome of Mycobacterium tuberculosis (Mtb)[7]. The characteristics of Mtb isolates included in the RYOKEN 2007 nationwide anti-TB drug susceptibility study in Japan and the GReAT database were investigated
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