We sought to explore the evolutionary history ofMycobacterium tuberculosis Latin American & Mediterranean (L4.3/LAM) sublineage in Tunisia where it predominates.
We carried out high-resolution genotyping of 252 L4.3/LAM clinical strains and whole-genome sequenced 31 representative isolates.
Genotyping data coupled with Bayesian analyses split the Tunisian L4.3/LAM strain collection into two divergent entities (65.07% vs 34.92%), a major subpopulation, chiefly dominated by a single clonal complex (CC), TUN4.3_CC1 (94.51%), and a minor subpopulation, mainly represented by TUN4.3_CC2 (42.04%). TUN4.3_CC1 is thus remarkably thriving in Tunisia, accounting for 61.5% of the L4.3/LAM sublineage. TUN4.3_CC1 displayed a higher mean allelic richness compared to TUN4.3_CC2, and predominated throughout the whole region, indicating a long-established history. The very low proportion of drug resistance among TUN4.3_CC1 isolates argues towards its intrinsic ability to spread successfully in the host population. Genomic analyses further confirmed the clear genetic separation between the two main CCs (pairwise fixation index,F, of 0.56), and suggested the relatively ancient origin of TUN4.3_CC1. Consistent with its successful expansion, TUN4.3_CC1 showed reduced mean pairwise genetic distance among genomes.
Our findings link the successful expansion of L4.3/LAM in Tunisia to a single, most likely long-established clone.

Copyright © 2020. Published by Elsevier Ltd.