Revised nomenclature and SNP barcode for Mycobacterium tuberculosis 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.