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

Abstract

Contrarily to other lineages such as L2 and L4, there are still scarce whole-genome-sequence data on L5-L6 MTBC clinical isolates in public genomes repositories. Recent results suggest a high complexity of L5 history in Africa. It is of importance for an adequate assessment of TB infection in Africa, that is still related to the presence of L5-L6 MTBC strains. This study reports a significant improvement of our knowledge of L5 diversity, phylogeographical history, and global population structure of Mycobacterium africanum L5. To achieve this aim, we sequenced new clinical isolates from Northern Nigeria and from proprietary collections, and used a new powerful bioinformatical pipeline, TB-Annotator that explores not only the shared SNPs but also shared missing genes, identical IS6110 insertion sites and shared regions of deletion. This study using both newly sequenced genomes and available public genomes allows to describe new L5 sublineages. We report that the MTBC L5 tree is made-up of at least 12 sublineages from which 6 are new descriptions. We confront our new classification to the most recent published one and suggest new naming for the discovered sublineages. Finally, we discuss the phylogeographical specificity of sublineages 5.1 and sublineage 5.2 and suggest a new hypothesis of L5-L6 emergence in Africa.

Mycobacterium tuberculosis complex drug-resistance, phylogenetics, and evolution in Nigeria: Comparison with Ghana and Cameroon

“…As such, the newly sequenced isolates described in this paper, and submitted to the NCBI, allow to deepen our understanding of the genomic diversity of Lineage5, especially concerning the discovery of rarer sublineages of L5. The names of the lineages in this description follow the thorough nomenclature of [ 13 ], with a link to [ 1 ]. We do not find L5.3, which is not surprising, considering the rarity of this lineage.…”

“…We had hoped to be able to sequence more L5-L6 isolates, but because of a trend towards the disappearance of these lineages in this region of the world and the difficulties in growing, we were only able for the time-being to sequence about twenty five L5-L6 from DNA archives and from this cohort, and fourteen L4 isolates. The new L5 isolates sequenced, belong to rare sublineages, and are described in detail elsewhere [ 13 ]. Concerning L4.6.2.2, this study confirms their specific drug-resistance status and the interest to study them further apart at a larger scale to look for epidemiological clusters in defined settings, because they are a serious concern for public health in Nigeria.…”

“…Sublineage information from the Coscolla et al . scheme [ 1 ] has been applied to isolates of Lineages 5 and 6, and it has been compared to the new proposal for L5 taxonomy published in [ 13 ]. DNA alignments of SNPs have been extracted for the following datasets:…”

“…Lineage attribution has been done by using the robust SNP barcode for typing Mycobacterium tuberculosis complex isolates of Coll et al [4], as developed in the TB-Annotator platform. Sublineage information from the Coscolla et al scheme [1] has been applied to isolates of Lineages 5 and 6, and it has been compared to the new proposal for L5 taxonomy published in [13]. DNA alignments of SNPs have been extracted for the following datasets:…”

“…Using a new cohort of 325 patients representing the diversity of the north of the country (as collected in the Kano region, with available simultaneous DNA availability and clinical information on half, i.e. 165 patients), the specific sequencing by Illumina of 24 isolates of this region (mainly, L5 and L6, among which fifteen L5 sequences were submitted to the NCBI [ 13 ], this article will seek to provide some answers to the following questions: do we observe the same distribution of L4 or L5 sublineages in Nigeria as in two neighboring countries, Ghana and Cameroun and can we infer some results on L4.6.2 origin? To which specific sublineages of L4 or L5 is the emergence and transmission of antimicrobial resistance associated and what do newly sequenced isolates tell us about these lineages, regardless of the country where they were obtained.…”