Codeine dysregulates ribosome biogenesis in Escherichia coli with DNA double-strand breaks to chart path to new classes of antibiotics.
Future Drug Discov
; 5(3): FDD84, 2023 Sep.
Article
en En
| MEDLINE
| ID: mdl-38464684
ABSTRACT
Aim:
A bacterial genetics-guided approach was utilized for the discovery of new compounds affecting bacterial genome stability. Materials &methods:
Fungal extracts and fractions were tested for genome instability-mediated antibacterial activity. Interaction assays and RT-qPCR were used to identify compounds that boost the activity of sub-minimum inhibitory concentration streptomycin and obtain insights on the molecular mechanisms of the primary hit compound, respectively.Results:
Several extracts and fractions caused bacterial genome instability. Codeine, in synergy with streptomycin, regulates double-strand break (DSB) repair and causes bacterial ribosome dysfunction in the absence of DSBs, and dysregulation of ribosome biogenesis in a DSB-dependent manner.Conclusion:
This study demonstrates a potential viable strategy that we are exploring for the discovery of new chemical entities with activities against Escherichia coli and other bacterial pathogens.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Future Drug Discov
Año:
2023
Tipo del documento:
Article
País de afiliación:
Ghana
Pais de publicación:
Reino Unido