Tadesse Michaël Dagne, Ali Nala, White Martha, Song Lijiang, Alberti Fabrizio, Sagona Antonia P
School of Life Sciences, University of Warwick, Coventry CV4 7AL, U.K.
Department of Chemistry, University of Warwick, Coventry CV4 7AL, U.K.
ACS Omega. 2025 Mar 18;10(12):12026-12036. doi: 10.1021/acsomega.4c09831. eCollection 2025 Apr 1.
The surge in antibiotic-resistant infections has been deemed a major public health concern. There is an urgent need for novel antimicrobial therapies, chemical and nonantibiotic. The basidiomycota-derived, secondary metabolite pleurotin has been shown to be effective against Gram-positive bacteria, while bacteriophages could be the ultimate nonantibiotic alternative. In this study, the combination of pleurotin and phage K targeting was examined. Pleurotin was isolated from the basidiomycota fungus . The cytotoxicity of pleurotin was assessed in two human cell lines in comparison to pleuromutilin, vancomycin, and phage K. The antibiotics were then tested independently or in combination with phage K against two strains. Cytotoxicity of pleurotin in human cells was comparable to vancomycin and pleuromutilin. Results suggest that adding phage K has a synergistic effect and can lower the MIC for pleurotin, pleuromutilin, and vancomycin. This demonstrates that pleurotin could be a viable antistaphylococcal drug.
抗生素耐药性感染的激增已被视为一个重大的公共卫生问题。迫切需要新型抗菌疗法，包括化学和非抗生素类疗法。已证明担子菌衍生的次级代谢产物侧耳素对革兰氏阳性菌有效，而噬菌体可能是最终的非抗生素替代物。在本研究中，检测了侧耳素与靶向噬菌体K的组合。侧耳素是从担子菌真菌中分离出来的。与截短侧耳素、万古霉素和噬菌体K相比，在两种人类细胞系中评估了侧耳素的细胞毒性。然后分别测试了这些抗生素或与噬菌体K联合针对两种菌株的效果。侧耳素在人类细胞中的细胞毒性与万古霉素和截短侧耳素相当。结果表明，添加噬菌体K具有协同作用，可降低侧耳素、截短侧耳素和万古霉素的最低抑菌浓度。这表明侧耳素可能是一种可行的抗葡萄球菌药物。
