Delineating the evolutionary pathway to multidrug-resistant outbreaks of a Mycobacterium tuberculosis L4.1.2.1/Haarlem sublineage.

We sought to capture the evolutionary itinerary of the Mycobacterium tuberculosis L4.1.2.1/Haarlem sublineage, northern Tunisia, where it caused a major multidrug-resistant (MDR-TB) outbreak, in a context strictly negative for HIV infection. We combined whole genome sequencing and Bayesian approaches using a representative collection of drug-susceptible and drug-resistant L4.1.2.1/Haarlem clinical strains (n =121) recovered from the outbreak region over 16 years. In the absence of drug resistance, the L4.1.2.1/Haarlem sublineage showed a propensity for rapid transmission as witnessed by the high clustering (44.6%) and recent transmission rates (25%), as well as the reduced mean distance between genome pairs. The entire pool of L4.1.2.1/Haarlem MDR strains was found to be linked to either the aforementioned major outbreak (68 individuals, 2001-2016) or to a minor, newly uncovered outbreak (6 cases, 2001-2011). Strikingly, the two outbreaks descended independently from a common ancestor that can be dated back to 1886. Our data point to the intrinsic propensity for rapid transmission of the M. tuberculosis L4.1.2.1/Haarlem sublineage in northern Tunisia, linking the overall MDR-TB epidemic to a single ancestor. These findings bring out the important role of the bacillus's genetic background in the emergence of successful MDR M. tuberculosis clones.

Informations de copyright

Copyright © 2024. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.