Whole-genome sequencing reveals genetic signature of bedaquiline resistance in a clinical isolate of Mycobacterium tuberculosis

Objectives: The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis strains has opened up new challenges for tuberculosis (TB) control in India. This study examined molecular markers of resistance to bedaquiline, a new antituberculous drug with the potential to dramatically improve MDR-TB treatment outcomes and to reduce mortality. Methods: A clinical M. tuberculosis isolate with a MDR-TB profile was subjected to whole-genome sequencing using an Illumina NextSeq500 platform, followed by genome-wide sequence analysis. Results: A mutation in the Rv0678 coding region associated with in vitro bedaquiline resistance was identified. The strain represented the Delhi/CAS lineage. Conclusions: This first report of a potentially bedaquiline-resistant M. tuberculosis strain in India highlights the role of genome-wide sequence analysis of isolates from TB cases with a history of treatment in countries with a high burden of MDR-TB and XDR-TB.