A robust SNP barcode for typing Mycobacterium tuberculosis complex strains

Abstract

Strain-specific genomic diversity in the Mycobacterium tuberculosis complex (MTBC) is an important factor in pathogenesis that may affect virulence, transmissibility, host response and emergence of drug resistance. Several systems have been proposed to classify MTBC strains into distinct lineages and families. Here, we investigate single-nucleotide polymorphisms (SNPs) as robust (stable) markers of genetic variation for phylogenetic analysis. We identify ~92 k SNP across a global collection of 1,601 genomes. The SNP-based phylogeny is consistent with the gold-standard regions of difference (RD) classification system. Of the ~7 k strain-specific SNPs identified, 62 markers are proposed to discriminate known circulating strains. This SNP-based barcode is the first to cover all main lineages, and classifies a greater number of sublineages than current alternatives. It may be used to classify clinical isolates to evaluate tools to control the disease, including therapeutics and vaccines whose effectiveness may vary by strain type.

Figure 1. Global phylogeny of 1,601 MTBC isolates.

A total of 91,648 SNPs spanning the whole genome were used to reconstruct the phylogeny of 1,601 MTBC isolates. All seven main MTBC lineages are indicated at the inner area of the tree. The main sublineages are annotated at the outer arc along with lineage-specific RDs. Identified clades are colour coded.