Study of Stepwise Acquisition of and Mutations Conferring Bedaquiline Resistance.
Nabila Ismail, Nazir A Ismail, Shaheed V Omar, Remco P H Peters
Author Information
Nabila Ismail: Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, Prinshof, Gauteng, South Africa. ORCID
Nazir A Ismail: Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, Prinshof, Gauteng, South Africa.
Shaheed V Omar: WHO Supranational Tuberculosis Reference Laboratory, National Health Laboratory Service, National Institute for Communicable Diseases, Sandringham, Gauteng, South Africa.
Remco P H Peters: Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, Prinshof, Gauteng, South Africa rph.peters@gmail.com. ORCID
Bedaquiline resistance within may arise through efflux-based () or target-based () pathway mutations. mutant populations from each of five sequential steps in a passaging approach, using a pyrazinamide-resistant ATCC strain, were subjected to MIC determinations and whole-genome sequencing. Exposure to increasing bedaquiline concentrations resulted in increasing phenotypic resistance (up to >2 μg/ml) through MIC determination on solid medium (Middlebrook 7H10). mutations were dynamic, while mutations were fixed, once occurring. We present the following hypothesis for emergence of bedaquiline resistance: mutations may be the first transient step in low-level resistance acquisition, followed by high-level resistance due to fixed mutations.
