7th joint conference "Joint Microbiology & Infection Conference 2024" of the DGHM and VAAM

Abstract: M. tuberculosis lineage 2 is one of the most widely dispersed lineages in the world, and is particularly associated with the spread of multi-resistant strains in Eurasia. However, the reasons for the success of Lineage 2 are only partially understood. My presentation will develop and underline the importance of an integrative approach to answer this question. Firstly, using Bayesian phylogenomics and demogenetics analyses, based on hundreds or thousands of complete genomes, I will illustrate the strength, spread and timing of major L2 epidemics, which highlight and confirm the dominance of this lineage both in terms of antibiotic resistance and epidemiological success.  In addition, we will also see how major socio-economic events reinforce ongoing epidemics. In the second part, which focuses on the underlying mechanisms, I will summarize how predictive simulations, epidemicity indices, genome-wide association studies and, finally, laboratory fluctuation assays have enabled us to make progress on this subject.  
For example, we were able to show that the collapse of the Soviet Union and, later, the Russian economic crisis were the main drivers of epidemics rebounds. L2 strains showed a significant (P < 0.01) pattern of accelerating mutation rate along the tree branches, and this on a scale of only 30 years. Furthermore, fluctuation assays showed that modern Central Asian lineage 2 strains acquire rifampicin resistance about twice as fast as ancestral L2 or Lineage 4 strains. The same applies to bedaquiline, for which basal Beijing strains outperform L4 strains. The fact that L2-derived strains have significantly higher mutation rates than other lineages is likely to enhance their adaptive landscape, as well as their propensity to acquire resistance/compensatory mutations.  


Evolutionary history and adaptive landscape of the M. tuberculosis Beijing lineage

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