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Nigeria has an emerging problem with multidrug-resistant tuberculosis. Here, we describe the use of whole-genome sequencing to understand the epidemiology of tuberculosis and genetics of multi-drug resistance among patients from two tertiary referral centers in South West Nigeria. We found that most isolates of Mycobacterium tuberculosis from this setting belonged to the Cameroon clade within the Euro-American lineage. Phylogenetic analysis shows this clade is undergoing clonal expansion in this region, where it has been involved in inter-patient transmission of sensitive and multidrug-resistant tuberculosis. In some patients, genomic changes occurred in bacterial isolates during the course of treatment that resulted in decreased drug susceptibility. We conclude that inter-patient transmission of resistant isolates, principally from the Cameroon clade, contributes to the spread of MDR-TB in this setting, underscoring the urgent need to curb the spread of multi-drug resistance in this region. |