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Exploring the adaptative landscape and factors impacting the epidemic success of Mycobacterium tuberculosis lineage 2 using simulations and genomic analyses

N Gharbi(1,2) T Wirth(1,2)

1:EPHE, PSL University, Paris, France; 2:Institut de Systématique, Evolution, Biodiversité, ISYEB, Muséum national d’Histoire naturelle, CNRS, Sorbonne Université, EPHE, Université des Antilles, Paris, France

Mycobacterium tuberculosis (M.tb) lineage 2, known as the Beijing lineage, stands  out for its concerning contribution to the global  burden of tuberculosis (TB).  Compared to other lineages, it exhibits heightened virulence, drug resistance. To understand the factors propelling the epidemic success of M.tb lineage 2, this study employs a multifaceted approach that combines  forward-time genetic simulation, genomic, and epidemiological analyses. Initially, we sought to detect signals of possible mutation rate acceleration between lineage 2 and lineage 4 strains, based on the mutational parameters described by Ford et al. (2015). Using predictive simulations with SLIM and replicating demographic parameters close to recent outbreaks in both lineages, we assessed the ability of Bayesian phylogenomic methods, in particular using the BEAST algorithm, to discern potential rate accelerations during outbreaks, while accounting for demographic influences. By comparing lineages using Bayesian analyses of genomic data from recent epidemics, we demonstrated that the Beijing lineage has significantly higher mutation rates than the L4 lineage. Our subsequent objective was to disentangle the interaction of genetic background and socio-economic factors on the epidemic success of Mycobacterium tuberculosis complex (MTBC) strains, using the time-scaled haplotypic density (THD) index. This index was calculated on a comprehensive collection of 12,289 whole Mycobacterium tuberculosis genomes from various  geographical regions and was compared on a global scale, as well as for lineage 2 only.

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