Mutations in <i>fbiD</i> ( <i>Rv2983</i> ) as a Novel Determinant of Resistance to Pretomanid and Delamanid in Mycobacterium tuberculosis
Dalin Rifat, Si-Yang Li, Thomas R. Ioerger, Keshav V. Shah, Jean‐Philippe Lanoix, Jin Lee, Ghader Bashiri, James C. Sacchettini, Eric L. Nuermberger
Abstract
The nitroimidazole prodrugs delamanid and pretomanid comprise one of only two new antimicrobial classes approved to treat tuberculosis (TB) in 50 years. Prior in vitro studies suggest a relatively low barrier to nitroimidazole resistance in Mycobacterium tuberculosis , but clinical evidence is limited to date. We selected pretomanid-resistant M. tuberculosis mutants in two mouse models of TB using a range of pretomanid doses. The frequency of spontaneous resistance was approximately 10 −5 CFU.
Topics & Concepts
Mycobacterium tuberculosisTuberculosisMicrobiologyGeneticsMutationBiologyVirologyMedicineGenePathologyTuberculosis Research and EpidemiologyMycobacterium research and diagnosisDiagnosis and treatment of tuberculosis