Characterization of Genomic Variants Associated with Resistance to Bedaquiline and Delamanid in Naive Mycobacterium tuberculosis Clinical Strains
Simone Battaglia, Andrea Spitaleri, Andrea Maurizio Cabibbe, Conor J. Meehan, Christian Utpatel, Nazir Ismail, Sabira Tahseen, Alena Skrahina, Natavan Alikhanova, S. M. Mostofa Kamal, A. I. Barbova, Stefan Niemann, Ramona Groenheit, Anna Dean, Matteo Zignol, Leen Rigouts, Daniela María Cirillo
Abstract
The role of mutations in genes associated with phenotypic resistance to bedaquiline (BDQ) and delamanid (DLM) in Mycobacterium tuberculosis complex (MTBc) strains is poorly characterized. A clear understanding of the genetic variants’ role is crucial to guide the development of molecular-based drug susceptibility testing (DST). In this work, we analyzed all mutations in candidate genomic regions associated with BDQ- and DLM-resistant phenotypes using a whole-genome sequencing (WGS) data set from a collection of 4,795 MTBc clinical isolates from six countries with a high burden of tuberculosis (TB).