Abstract
Multidrug resistant tuberculosis (MDR-TB) epidemics are sustained by transmission of reproductively fit MDR M. tuberculosis (Mtb) strains. We search a large publicly available dataset of ~200,000 Mtb whole genome sequences to identify strains related to a highly successful MDR clade circulating in Moldova belonging to lineage 4.2.1/Ural. We characterize a clade of 1604 drug-resistant Mtb sequences harboring conserved resistance-conferring mutations. We identify the Russian Federation as the most likely country of origin for this clade and infer several independent migration events from Russia and Moldova to other European and Asian countries. We estimate that this clade is expanding more rapidly than comparable clades of lineage 4.2.1/Ural. The broad dispersal of this highly successful clade is an urgent global health threat. Genomic surveillance is essential to track the evolution and spread of this and other strains of concern.
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Data availability
All data were accessed from the European Nucleotide Archive. Run accession numbers, country of origin, and inferred sample dates are available in Supplementary Data 1.
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Acknowledgements
The authors report funding from the National Institutes of Health (R01AI180209: M.H.C., B.P., T.C., B.S., and P01AI159402: M.H.C., T.C., and B.S.), and the Medical Research Council (UKRI1414: B.S.).
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C.C. and B.S. conceived the study. IR and YTC assembled the data. M.H.C., Y.S., and B.S. analyzed the data. M.H.C., Y.S., B.I.P., and B.S. visualized results. T.C. secured funding. M.H.C., I.R., Y.S., B.I.P., Y.T.C., N.C., V.C., C.C., T.C., and B.S. reviewed results, contributed to manuscript drafting, and revised the manuscript.
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Chitwood, M.H., Rancu, I., Song, Y. et al. The global phylogeography of rapidly expanding multidrug resistant Ural lineage 4.2 Mycobacterium tuberculosis. Nat Commun (2026). https://doi.org/10.1038/s41467-026-71193-6
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DOI: https://doi.org/10.1038/s41467-026-71193-6
