The global phylogeography of rapidly expanding multidrug resistant Ural lineage 4.2 Mycobacterium tuberculosis

Multidrug resistant tuberculosis (MDR-TB) is a leading global health challenge. Recent studies identified a reproductively fit Ural lineage 4.2 MDR M. tuberculosis ( Mtb ) variant circulating within the Republic of Moldova. We searched a large publicly available dataset of ∼200,000 Mtb whole genome sequences and identified a clade of 1604 drug-resistant Mtb sequences harboring conserved resistance-conferring mutations that are closely related to the MDR Mtb variant circulating in Moldova. We identified the Russian Federation as the most likely country of origin for this clade, and we inferred several independent migration events from Russia and Moldova to other former Soviet Republics and several European countries. Using local branching index, we found that this clade is expanding more rapidly than comparable clades of lineage 4.2. This evolutionarily successful strain’s presence beyond Moldova poses a threat to MDR-TB control, and enhanced surveillance is necessary to reduce the risk of MDR-TB epidemics in the region. Funding The authors report funding from the National Institutes of Health (R01AI180209, P01AI159402)