Dataset Information

Transcontinental spread and evolution of Mycobacterium tuberculosis W148 European/Russian clade toward extensively drug resistant tuberculosis.

ABSTRACT: Transmission-driven multi-/extensively drug resistant (M/XDR) tuberculosis (TB) is the largest single contributor to human mortality due to antimicrobial resistance. A few major clades of the Mycobacterium tuberculosis complex belonging to lineage 2, responsible for high prevalence of MDR-TB in Eurasia, show outstanding transnational distributions. Here, we determined factors underlying the emergence and epidemic spread of the W148 clade by genome sequencing and Bayesian demogenetic analyses of 720 isolates from 23 countries. We dated a common ancestor around 1963 and identified two successive epidemic expansions in the late 1980s and late 1990s, coinciding with major socio-economic changes in the post-Soviet Era. These population expansions favored accumulation of resistance mutations to up to 11 anti-TB drugs, with MDR evolving toward additional resistances to fluoroquinolones and second-line injectable drugs within 20 years on average. Timescaled haplotypic density analysis revealed that widespread acquisition of compensatory mutations was associated with transmission success of XDR strains. Virtually all W148 strains harbored a hypervirulence-associated ppe38 gene locus, and incipient recurrent emergence of prpR mutation-mediated drug tolerance was detected. The outstanding genetic arsenal of this geographically widespread M/XDR strain clade represents a "perfect storm" that jeopardizes the successful introduction of new anti-M/XDR-TB antibiotic regimens.

SUBMITTER: Merker M

PROVIDER: S-EPMC9426364 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Transcontinental spread and evolution of Mycobacterium tuberculosis W148 European/Russian clade toward extensively drug resistant tuberculosis.

Merker Matthias M Rasigade Jean-Philippe JP Barbier Maxime M Cox Helen H Feuerriegel Silke S Kohl Thomas A TA Shitikov Egor E Klaos Kadri K Gaudin Cyril C Antoine Rudy R Diel Roland R Borrell Sonia S Gagneux Sebastien S Nikolayevskyy Vladyslav V Andres Sönke S Crudu Valeriu V Supply Philip P Niemann Stefan S Wirth Thierry T

Nature communications 20220830 1

Transmission-driven multi-/extensively drug resistant (M/XDR) tuberculosis (TB) is the largest single contributor to human mortality due to antimicrobial resistance. A few major clades of the Mycobacterium tuberculosis complex belonging to lineage 2, responsible for high prevalence of MDR-TB in Eurasia, show outstanding transnational distributions. Here, we determined factors underlying the emergence and epidemic spread of the W148 clade by genome sequencing and Bayesian demogenetic analyses of ...[more]

PMID: 36042200

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Project description:Livestock production is a fundamental pillar of the Moroccan economy. Infectious diseases of cattle and other species represent a significant threat to the livestock industry, animal health, and food safety. Bovine tuberculosis (bTB), mainly caused by Mycobacterium bovis, generates considerable direct and indirect economic losses, and an underestimated human health burden caused by zoonotic transmission. Previous studies have suggested likely M. bovis transmission links between Morocco and Southern Europe, however, limitations inherent with the methods used prevented definitive conclusions. In this study, we employed whole genome sequencing analysis to determine the genetic diversity of the first 55 M. bovis whole-genomes in Morocco and to better define the phylogenetic links between strains from Morocco and a large dataset from related and neighboring countries. With a total of 780 M. bovis sequences extracted from cattle, wildlife or humans and representing 36 countries, we discovered two new M bovis spoligotypes in Morocco and that the Moroccan clonal complexes are classified as belonging to Europe or Unknown, supporting previous studies that the Sahara Desert might be playing a key role in preventing M. bovis transmission between North Africa and Sub-Saharan Africa. Furthermore, our analysis showed a close M. bovis genetic relationship between cattle from Morocco and cattle from Spain, France, Portugal and Germany, and from cattle in Morocco and humans in Italy, Germany, and the UK. These results suggest that animal trade and human migration between Morocco and these countries might be playing a role in disease transmission. Our study benefits from a large sample size and a rich dataset that includes sequences from cattle, wildlife and humans from Morocco and neighboring countries, enabling the delineation of M. bovis genetic links across countries and host-species. Our study calls for further investigation of animal and zoonotic TB spread in Morocco and in other countries, which is important to inform future TB control measures at the animal-human interface.

Dataset Information

Transcontinental spread and evolution of Mycobacterium tuberculosis W148 European/Russian clade toward extensively drug resistant tuberculosis.

Publications

Transcontinental spread and evolution of Mycobacterium tuberculosis W148 European/Russian clade toward extensively drug resistant tuberculosis.

Similar Datasets

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