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Codeine dysregulates ribosome biogenesis in Escherichia coli with DNA double-strand breaks to chart path to new classes of antibiotics.
Amarh, Vincent; Abbey, Benaiah Annertey; Acheampong, Samuel Akwasi; Debrah, Michael Acheampong; Amarquaye, Gwendolyn Nita; Arthur, Patrick Kobina.
Afiliación
  • Amarh V; Department of Biochemistry, Cell & Molecular Biology, West African Center for Cell Biology of Infectious Pathogens, University of Ghana, PO Box LG54, Legon, Accra, Ghana.
  • Abbey BA; Department of Biochemistry, Cell & Molecular Biology, West African Center for Cell Biology of Infectious Pathogens, University of Ghana, PO Box LG54, Legon, Accra, Ghana.
  • Acheampong SA; Department of Biochemistry, Cell & Molecular Biology, West African Center for Cell Biology of Infectious Pathogens, University of Ghana, PO Box LG54, Legon, Accra, Ghana.
  • Debrah MA; Department of Biochemistry, Cell & Molecular Biology, West African Center for Cell Biology of Infectious Pathogens, University of Ghana, PO Box LG54, Legon, Accra, Ghana.
  • Amarquaye GN; Department of Biochemistry, Cell & Molecular Biology, West African Center for Cell Biology of Infectious Pathogens, University of Ghana, PO Box LG54, Legon, Accra, Ghana.
  • Arthur PK; Department of Biochemistry, Cell & Molecular Biology, West African Center for Cell Biology of Infectious Pathogens, University of Ghana, PO Box LG54, Legon, Accra, Ghana.
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.
Palabras clave

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

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