Global diversity of M. Tuberculosis

Figure 1: Global diversity of Mycobacterium tuberculosis (Mtb). Main lineages of Mtb are associated with different parts of the world (adapted from Gagneux et al. PNAS 2006).

Genetic Differences

We have previously shown that Mtb consists of six phylogenetically distinct lineages which are associated with different regions of the world (Figure 1). Currently, we are using large-scale comparative DNA sequencing to study the nature of the genetic differences between these lineages and the evolutionary forces which shape this diversity.

Global Phylogeny

Recently, we published the first whole-genome based global phylogeny of Mtb (Figure 2). This phylogeny demonstrates that Mtb is more genetically diverse than previously believed, and supports the notion that human TB originated in Africa. Our ongoing work on the global strain diversity of Mtb is now focusing on geographic areas and human populations where no or only limited data are available. A particular emphasis will be on sub-Saharan Africa and Asia where we hope to discover novel Mtb lineages.

Highly Conserved T Cell Antigens

Population genomic analyses of our whole genome data also revealed that, in contrast to most other human pathogens which evade host immune responses by accumulating antigenic variation, T cell antigens in Mtb are highly conserved. These findings have important implications for the development of new TB diagnostics and vaccines. Following on this observation, we are now screening for variable regions of the Mtb genome which might represent as yet unrecognised human antigens.

Novel Genotyping Approaches

We have used DNA sequencing to evaluate the phylogenetic performance of the current genotyping tools used for Mtb (i.e. spoligotyping and MIRU-VNTR). We found that while these tools are valuable for standard molecular epidemiological applications, they are inadequate for phylogenetic and population genetic analyses of Mtb. Hence we are now developing novel single nucleotide polymorphism based genotyping approaches for Mtb, which we will implement in collaboration with partners in areas where TB is highly endemic.

Figure 2: Whole genome-based phylogeny of M. tuberculosis (adapted from Comas et al. Nature Genetics 2010).

Asare P et al. Genomic epidemiological analysis identifies high relapse among individuals with recurring tuberculosis and provides evidence of household recent TB transmission in Ghana. Int J Infect Dis. 2021(in press). DOI: 10.1016/j.ijid.2021.02.110

Coscolla M et al. Phylogenomics of Mycobacterium africanum reveals a new lineage and a complex evolutionary history. Microb Genom. 2021(in press). DOI: 10.1099/mgen.0.000477

Guimarães A.E.D.S et al. Evaluation of drug susceptibility profile of Mycobacterium tuberculosis Lineage 1 from Brazil based on whole genome sequencing and phenotypic methods. Mem Inst Oswaldo Cruz. 2021;115:e200520. DOI: 10.1590/0074-02760200520

Hiza H et al. Case-control, diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood. BMJ. 2021(in press). DOI: 10.1101/2021.03.10.21253246

Ley S.D et al. Melting the eis: non-detection of kanamycin resistance markers by routine diagnostic tests and identification of new eis-promoter variants. Antimicrob Agents Chemother. 2021(in press). DOI: 10.1128/AAC.02502-20