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

•Propensity for rapid transmission of the L4.1.2.1 sublineage in northern Tunisia.•The L4.1.2.1 sublineage is the primary cause of multidrug-resistant tuberculosis outbreaks in northern Tunisia.•A single L4.1.2.1 ancestor clone fuels the overall multidrug-resistant tuberculosis epidemic. We sought t...

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Veröffentlicht in:International journal of infectious diseases 2024-07, Vol.144, p.107077-107077, Article 107077
Hauptverfasser: Dekhil, Naira, Mardassi, Helmi
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Sprache:eng
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Zusammenfassung:•Propensity for rapid transmission of the L4.1.2.1 sublineage in northern Tunisia.•The L4.1.2.1 sublineage is the primary cause of multidrug-resistant tuberculosis outbreaks in northern Tunisia.•A single L4.1.2.1 ancestor clone fuels the overall multidrug-resistant tuberculosis epidemic. We sought to capture the evolutionary itinerary of the Mycobacterium tuberculosis L4.1.2.1/Haarlem sublineage in northern Tunisia, where it caused a major multidrug-resistant (MDR) tuberculosis 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 (six 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 tuberculosis epidemic to a single ancestor. These findings bring out the important role of the bacillus’ genetic background in the emergence of successful MDR M. tuberculosis clones.
ISSN:1201-9712
1878-3511
DOI:10.1016/j.ijid.2024.107077