Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
J Antibiot (Tokyo). 2024 Aug;77(8):477-485. doi: 10.1038/s41429-024-00739-x. Epub 2024 May 21.
The development of novel antimicrobial agents is required to solve the problem of antimicrobial resistance. We established a quantitative method for evaluating the therapeutic efficacy of antimicrobial agents in a silkworm bacterial infection model. Pharmacokinetic factors are present in the silkworm as well as in mice, and evaluating the therapeutic efficacy of antimicrobial agents is possible in a silkworm infection model, comparable to that in a mammalian model. This silkworm model was used to screen for novel antimicrobial agents with therapeutic efficacy as an indicator. As a result, a new antibiotic, lysocin E, was discovered. Lysocin E has a completely different mechanism of action from existing antimicrobial agents, and its potent bactericidal activity leads to remarkable therapeutic efficacy in a mouse model. In this review, I describe the features of the silkworm model that have contributed to the discovery of lysocin E and its mechanisms of action.
需要开发新型抗菌药物来解决抗菌药物耐药性问题。我们建立了一种定量方法,用于评估抗菌药物在蚕细菌感染模型中的治疗效果。蚕和小鼠中都存在药代动力学因素,因此可以在蚕感染模型中评估抗菌药物的治疗效果,与哺乳动物模型相当。该蚕模型可用于以治疗效果为指标筛选具有疗效的新型抗菌药物。结果发现了一种新型抗生素,溶菌素 E。溶菌素 E 的作用机制与现有的抗菌药物完全不同,其强大的杀菌活性使其在小鼠模型中具有显著的治疗效果。在这篇综述中,我描述了对溶菌素 E 的发现有贡献的蚕模型的特点及其作用机制。