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In Vitro Study of Stepwise Acquisition of rv0678 and atpE Mutations Conferring Bedaquiline Resistance
- Source :
- Antimicrobial Agents and Chemotherapy, 63(8):ARTN e00292-19, 1-6. American Society for Microbiology
- Publication Year :
- 2019
- Publisher :
- American Society for Microbiology, 2019.
-
Abstract
- Bedaquiline resistance within Mycobacterium tuberculosis may arise through efflux-based (rv0678) or target-based (atpE) pathway mutations. M. tuberculosis 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 mu g/ml) through MIC determination on solid medium (Middlebrook 7H10). rv0678 mutations were dynamic, while atpE mutations were fixed, once occurring. We present the following hypothesis for in vitro emergence of bedaquiline resistance: rv0678 mutations may be the first transient step in low-level resistance acquisition, followed by high-level resistance due to fixed otpE mutations.
- Subjects :
- rv0678
Tuberculosis
Mutant
VARIANTS
Clofazimine
Mycobacterium tuberculosis
03 medical and health sciences
chemistry.chemical_compound
Mechanisms of Resistance
medicine
SYNTHASE
Pharmacology (medical)
bedaquiline
CLOFAZIMINE
030304 developmental biology
Pharmacology
0303 health sciences
biology
Strain (chemistry)
030306 microbiology
Chemistry
stepwise acquisition
biology.organism_classification
medicine.disease
Molecular biology
atpE
In vitro
Infectious Diseases
in vitro model
MYCOBACTERIUM-TUBERCULOSIS
Efflux
Bedaquiline
medicine.drug
Subjects
Details
- ISSN :
- 10986596 and 00664804
- Volume :
- 63
- Database :
- OpenAIRE
- Journal :
- Antimicrobial Agents and Chemotherapy
- Accession number :
- edsair.doi.dedup.....185fd3e94e0e8c991c0370e1b435c711