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

Abstract

By gathering 680 publicly available Sequence Read Archives from isolates of Mycobacterium tuberculosis complex (MTBC) including 190 belonging to the lineage 2 Beijing, and using an in-house bioinformatical pipeline, the TB-Annotator, that analyses more than 50 000 characters, we describe herein a new L2 sublineage from 20 isolates found in the Tochigi province, (Japan), that we designate as asia ancestral 5 (AAnc5). These isolates harbour a number of specific criteria (42 SNPs) and their intra-cluster pairwise distance suggests historical and not epidemiological transmission. These isolates harbour a mutation in rpoC, and do not fulfil, any of the modern Beijing lineage criteria, nor any of the other ancestral Beijing lineages described so far. Asia ancestral 5 isolates do not possess mutT2 58 and ogt 12 characteristics of modern Beijing, but possess ancestral Beijing SNPs characteristics. By looking into the literature, we found a reference isolate ID381, described in Kobe and Osaka belonging to the ‘G3’ group, sharing 36 out of the 42 specific SNPs found in AAnc5. We also assessed the intermediate position of the asia ancestral 4 (AAnc4) sublineage recently described in Thailand and propose an improved classification of the L2 that now includes AAnc4 and AAnc5. By increasing the recruitment into TB-Annotator to around 3000 genomes (including 642 belonging to L2), we confirmed our results and discovered additional historical ancestral L2 branches that remain to be investigated in more detail. We also present, in addition, some anthropological and historical data from Chinese and Japan history of tuberculosis, as well as from Korea, that could support our results on L2 evolution. This study shows that the reconstruction of the early history of tuberculosis in Asia is likely to reveal complex patterns since its emergence.

TB-annotator: a scalable web application that allowsin-depthanalysis of very large sets of publicly availableMycobacterium tuberculosiscomplex genomes

“…3.2.1 Connection between two historical tuberculosis outbreak sites in Japan, Honshu, by a new ancestral Mycobacterium tuberculosis L2 sublineage [62] In this study, we describe a historically endemic ancestral sublineage of L2, known as AAnc5, based on samples collected in the Tochigi Prefecture in central Japan. This sublineage is closely related to the Japanese G3 group identified in 2012 and is presumed to be named L2.2.A in a recent review.…”

An updated evolutionary history and taxonomy ofMycobacterium tuberculosislineage 5, also calledM. africanum

“…Figure 1 shows the general algorithm that was used to process the Short Read Archives (SRA) produced in house or recovered in public repositories. A brief description of the pipeline can be found in (Guyeux et al, 2022)…”

“…Because of complexity issues, this is done only for clusters of size (< 200 isolates). The unrooted tree was built using a similar approach as the one published in (Guyeux et al, 2022). Briefly, we used RAxML on a multi fasta-file produced using TB-Annotator; our files initially 10 10 contained 15901 SRAs at start, the bincat model was used instead of the GTR model and no outgroup was chosen ( S t a m a t a k i s , 2 0 1 4 ) .…”

“…Figure 1 shows the general algorithm that was used to process the Short Read Archives (SRA) produced in house or recovered in public repositories. A brief description of the pipeline can be found in (Guyeux et al, 2022). At the time of writing, the V1 database contained 15909 SRA; results were also checked in part using the expanded V2 version (Senelle et al in preparation).…”

Investigating the Diversity of Tuberculosis Spoligotypes with Dimensionality Reduction and Graph Theory

“…Analysis of presence of each of these spacers was called “spoligotyping” [ 3 ], and this popular technique has help to the understanding of the MTC diversity [ 4 , 5 ]. The more recent appearance of whole genome sequencing has revealed the existence of six major lineages comprising numerous sub-lineages [ 6 , 7 , 8 , 9 , 10 ], which have frequently been found to be in phase with previously discovered spoligotype patterns, despite the presence of convergent or imprecise events that occasionally confound the information carried by the latter.…”