A nutrient-limited screen unmasks rifabutin hyperactivity for extensively drug-resistant Acinetobacter baumannii.
Nat Microbiol
; 5(9): 1134-1143, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-32514072
ABSTRACT
Industry screens of large chemical libraries have traditionally relied on rich media to ensure rapid bacterial growth in high-throughput testing. We used eukaryotic, nutrient-limited growth media in a compound screen that unmasked a previously unknown hyperactivity of the old antibiotic, rifabutin (RBT), against highly resistant Acinetobacter baumannii. In nutrient-limited, but not rich, media, RBT was 200-fold more potent than rifampin. RBT was also substantially more effective in vivo. The mechanism of enhanced efficacy was a Trojan horse-like import of RBT, but not rifampin, through fhuE, only in nutrient-limited conditions. These results are of fundamental importance to efforts to discover antibacterial agents.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nutrientes
/
Rifabutina
/
Farmacorresistência Bacteriana Múltipla
/
Acinetobacter baumannii
/
Antibacterianos
Limite:
Animals
Idioma:
En
Revista:
Nat Microbiol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos