In Vitro Study of Stepwise Acquisition of rv0678 and atpE Mutations Conferring Bedaquiline Resistance.
Antimicrob Agents Chemother
; 63(8)2019 08.
Article
em En
| MEDLINE
| ID: mdl-31138569
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 µg/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 atpE mutations.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
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Farmacorresistência Bacteriana
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Diarilquinolinas
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Mutação
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Mycobacterium tuberculosis
Idioma:
En
Revista:
Antimicrob Agents Chemother
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
África do Sul