Laboratory of Gene Technology, Department of Biosystems, KU Leuven, 3001 Leuven, Belgium; Department of Bacteriology and Immunology, Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland; Department of Microbiology, Faculty of Agriculture and Forestry, University of Helsinki, 00790 Helsinki, Finland.
Laboratory of Gene Technology, Department of Biosystems, KU Leuven, 3001 Leuven, Belgium.
Curr Opin Biotechnol. 2021 Apr;68:1-7. doi: 10.1016/j.copbio.2020.08.015. Epub 2020 Sep 29.
The deeply intertwined evolutionary history between bacteriophages and bacteria has endowed phages with highly specific mechanisms to hijack bacterial cell metabolism for their propagation. Here, we present a comprehensive, phage-driven strategy to reveal novel antibacterial targets by the exploitation of phage-bacteria interactions. This strategy will enable the design of small molecules, which mimic the inhibitory phage proteins, and allow the subsequent hit-to-lead development of these antimicrobial compounds. This proposed small molecule approach is distinct from phage therapy and phage enzyme-based antimicrobials and may produce a more sustainable generation of new antibiotics that exploit novel bacterial targets and act in a pathogen-specific manner.
噬菌体与细菌之间复杂的进化史赋予了噬菌体高度特异的机制，使其能够劫持细菌的细胞代谢来进行自我繁殖。在这里，我们提出了一种全面的、由噬菌体驱动的策略，通过利用噬菌体-细菌的相互作用来揭示新的抗菌靶标。该策略将能够设计模仿抑制噬菌体蛋白的小分子，从而促进这些抗菌化合物的先导化合物优化。与噬菌体治疗和基于噬菌体酶的抗菌药物不同，这种小分子方法可能会产生更可持续的新一代抗生素，利用新的细菌靶标并以病原体特异性的方式发挥作用。
