Nyhamar Ellisiv, Webber Paige, Liong Olivia, Yilmaz Özgenur, Pajunen Maria, Skurnik Mikael, Wan Xing
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.
Antibiotics (Basel). 2023 Jul 21;12(7):1213. doi: 10.3390/antibiotics12071213.
In the escalating battle against antimicrobial resistance, there is an urgent need to discover and investigate new antibiotic strategies. Bacteriophages are untapped reservoirs of such potential antimicrobials. This study focused on Hypothetical Proteins of Unknown Function (HPUFs) from a phage Stab21. We examined its HPUFs for bactericidal activity against using a Next Generation Sequencing (NGS)-based approach. Among the 96 HPUFs examined, 5 demonstrated cross-species toxicity towards , suggesting the presence of shared molecular targets between and . One toxic antibacterial HPUF (toxHPUF) was found to share homology with a homing endonuclease. The implications of these findings are profound, particularly given the potential broad applicability of these bactericidal agents. This study confirms the efficacy of NGS in streamlining the screening process of toxHPUFs, contributes significantly to the ongoing exploration of phage biology, and offers promises in the search for potent antimicrobial agents.
在对抗抗菌素耐药性的这场不断升级的战斗中，迫切需要发现和研究新的抗生素策略。噬菌体是这类潜在抗菌剂尚未开发的宝库。本研究聚焦于来自噬菌体Stab21的未知功能假设蛋白（HPUFs）。我们使用基于下一代测序（NGS）的方法检测了其HPUFs对[具体细菌]的杀菌活性。在所检测的96种HPUFs中，有5种对[具体细菌]表现出跨物种毒性，这表明[具体细菌]和[另一具体细菌]之间存在共同的分子靶点。发现一种有毒的抗菌HPUF（toxHPUF）与一种归巢内切酶具有同源性。这些发现的意义深远，特别是考虑到这些杀菌剂可能具有广泛的适用性。本研究证实了NGS在简化toxHPUFs筛选过程中的有效性，为正在进行的噬菌体生物学探索做出了重大贡献，并为寻找强效抗菌剂带来了希望。
