Abstract
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.
Highlights
With 9.9 million new cases in 2019, and 500,000 multi-drug resistant cases, tuberculosis (TB) is far from being eradicated [1]
We described the genetic characterization of a new L2 sublineage from Japan, named asia ancestral 5 (AAnc5), that appears to be exclusive from Japan for the time-being
Regarding the set-up of the platform, the processes are the following: SRAs of interest are selected and kept only provided a certain number of conditions that together reinforce the reliability of the data: they must have read length>75bp, clean reads file must be at least 100 Mo, and CRISPR could be reconstructed using CRISPRbuilder-TB [54]
Summary
With 9.9 million new cases in 2019, and 500,000 multi-drug resistant cases, tuberculosis (TB) is far from being eradicated [1]. Among 9 acknowledged lineages (L1 to L9) described in Mycobacterium tuberculosis complex, the lineage L2 is of great interest [26]. Very large outbreaks in L2 were shown to have independently emerged worldwide [7]. L2 origin is suspected to be in China and L2 is predominant in east Asia, its exact place and time of emergence are still highly debated [8,9,10]. L2 clinical isolates have developed specific virulence and drug-resistance features that contribute to their epidemic This was achieved progressively and through the combination of polymorphic markers analysis such as IS6110RFLP1, MIRU-VNTR2, Regions of Difference (RD), hypervariable VNTR loci, and lastly whole-genome sequencing (WGS) [21,22,23,24,25,26,27]
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