Hamamoto Hiroshi, Urai Makoto, Paudel Atmika, Horie Ryo, Murakami Kazuhisa, Sekimizu Kazuhisa
Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Yakugaku Zasshi. 2012;132(1):79-84. doi: 10.1248/yakushi.132.79.
Most antibiotics obtained by in vitro screening with antibacterial activity have inappropriate properties as medicines due to their toxicity and pharmacodynamics in animal bodies. Thus, evaluation of the therapeutic effects of these samples using animal models is essential in the crude stage. Mammals are not suitable for therapeutic evaluation of a large number of samples due to high costs and ethical issues. We propose the use of silkworms (Bombyx mori) as model animals for screening therapeutically effective antibiotics. Silkworms are infected by various pathogenic bacteria and are effectively treated with similar ED(50) values of clinically used antibiotics. Furthermore, the drug metabolism pathways, such as cytochrome P450 and conjugation systems, are similar between silkworms and mammals. Silkworms have many advantages compared with other infection models, such as their 1) low cost, 2) few associated ethical problems, 3) adequate body size for easily handling, and 4) easier separation of organs and hemolymph. These features of the silkworm allow for efficient screening of therapeutically effective antibiotics. In this review, we discuss the advantages of the silkworm model in the early stages of drug development and the screening results of some antibiotics using the silkworm infection model.
大多数通过体外筛选获得的具有抗菌活性的抗生素，由于其在动物体内的毒性和药效学性质，作为药物具有不合适的特性。因此，在粗提阶段使用动物模型评估这些样品的治疗效果至关重要。由于成本高昂和伦理问题，哺乳动物不适合用于大量样品的治疗评估。我们建议使用家蚕（Bombyx mori）作为筛选具有治疗效果抗生素的模型动物。家蚕会受到各种病原菌的感染，并且使用临床使用抗生素的类似半数有效剂量（ED50）值可以有效治疗。此外，家蚕和哺乳动物之间的药物代谢途径，如细胞色素P450和结合系统，是相似的。与其他感染模型相比，家蚕具有许多优势，例如它们：1）成本低，2）相关伦理问题少，3）体型适中便于操作，4）器官和血淋巴易于分离。家蚕的这些特性使得能够高效筛选具有治疗效果的抗生素。在这篇综述中，我们讨论了家蚕模型在药物开发早期阶段的优势以及使用家蚕感染模型对一些抗生素的筛选结果。
