Amarh Vincent, Abbey Benaiah Annertey, Acheampong Samuel Akwasi, Debrah Michael Acheampong, Amarquaye Gwendolyn Nita, Arthur Patrick Kobina
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. 2023 Sep;5(3):FDD84. doi: 10.4155/fdd-2023-0005. Epub 2023 Oct 11.
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.
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.
This study demonstrates a potential viable strategy that we are exploring for the discovery of new chemical entities with activities against and other bacterial pathogens.
采用细菌遗传学指导的方法来发现影响细菌基因组稳定性的新化合物。
测试真菌提取物和馏分的基因组不稳定性介导的抗菌活性。分别使用相互作用测定和RT-qPCR来鉴定增强亚最小抑菌浓度链霉素活性的化合物，并深入了解主要命中化合物的分子机制。
几种提取物和馏分导致细菌基因组不稳定。可待因与链霉素协同作用，调节双链断裂（DSB）修复，并在不存在DSB的情况下导致细菌核糖体功能障碍，以及以DSB依赖的方式导致核糖体生物合成失调。
本研究展示了一种潜在可行的策略，我们正在探索用该策略发现对[未提及的细菌病原体]和其他细菌病原体具有活性的新化学实体。
