Revised nomenclature and SNP barcode for Mycobacterium tuberculosis lineage 2

Abstract

Mycobacterium tuberculosis (Mtb) lineage 2 (L2) strains are present globally, contributing to a widespread tuberculosis (TB) burden, particularly in Asia where both prevalence of TB and numbers of drug resistant TB are highest. The increasing availability of whole-genome sequencing (WGS) data worldwide provides an opportunity to improve our understanding of the global genetic diversity of Mtb L2 and its association with the disease epidemiology and pathogenesis. However, existing L2 sublineage classification schemes leave >20 % of the Modern Beijing isolates unclassified. Here, we present a revised SNP-based classification scheme of L2 in a genomic framework based on phylogenetic analysis of >4000 L2 isolates from 34 countries in Asia, Eastern Europe, Oceania and Africa. Our scheme consists of over 30 genotypes, many of which have not been described before. In particular, we propose six main genotypes of Modern Beijing strains, denoted L2.2.M1–L2.2.M6. We also provide SNP markers for genotyping L2 strains from WGS data. This fine-scale genotyping scheme, which can classify >98 % of the studied isolates, serves as a basis for more effective monitoring and reporting of transmission and outbreaks, as well as improving genotype-phenotype associations such as disease severity and drug resistance. This article contains data hosted by Microreact.

Whole-genome single nucleotide variant phylogenetic analysis of Mycobacterium tuberculosis Lineage 1 in endemic regions of Asia and Africa

“…This has implications for the utility of genetic tests for diagnosis of drug-resistant TB. Finally, genetic clusters in L1 are rare and small in size, suggesting a more limited transmission potential of L1, especially in comparison with L2 21 .…”

Connection between two historical tuberculosis outbreak sites in Japan, Honshu, by a new ancestral Mycobacterium tuberculosis L2 sublineage

“…3 ) . Among those, are the ‘K’ strain (part of AAnc1), the ‘L2.2.1.2’, the L2.2.E [ 30 , 31 , 80 ], and the AAnc5 recently designated as L2.2.A [ 31 ].…”

“…We describe in this paper a historical endemic ancestral sublineage of L2 based on samples collected in central Japan, Tochigi Prefecture, former Shimotsuke province, that we named AAnc5. This sublineage is highly related to the Japanese G3 group defined in 2012 [ 39 ] and assumed to be named L2.2.A in a recent review [ 31 ]. Our results strengthens the phylogenetical relevance of this sublineage into the global L2 evolutionary history and shows that it was transmitted historically in several Japanese cities.…”

“…According to the most recent review on L2 population structure based on more than 5000 genomes, AAnc5 or L2.2.A ‘is the most basal clade of L2.2.1 and comprises isolates almost entirely from Japan. The deep- branching structure of L2.2.A is suggestive of a previously unrecognized endemic strain ’ [ 31 ]. Since Japan is an island, and a country with a very low current tuberculosis prevalence rate (13 per 100 000 in 2017), it is an excellent setting to identify the historical events linked to past tuberculosis outbreaks [ 68 ].…”

“…Since Japan is an island, and a country with a very low current tuberculosis prevalence rate (13 per 100 000 in 2017), it is an excellent setting to identify the historical events linked to past tuberculosis outbreaks [ 68 ]. The increasing number of available genomes allows more and more L2 sublineages to be discovered, however their intimate historical and epidemiological relationships remains to be studied in more detail [ 30 , 31 ].…”