Panthee Suresh, Paudel Atmika, Hamamoto Hiroshi, Sekimizu Kazuhisa
Institute of Medical Mycology, Teikyo University Tokyo, Japan.
Front Microbiol. 2017 Mar 7;8:373. doi: 10.3389/fmicb.2017.00373. eCollection 2017.
The demand for novel antibiotics to combat the global spread of multi drug-resistant pathogens continues to grow. Pathogenic bacteria and fungi that cause fatal human infections can also kill silkworms and the infected silkworms can be cured by the same antibiotics used to treat infections in the clinic. As an invertebrate model, silkworm model is characterized by its convenience, low cost, no ethical issues. The presence of conserved immune response and similar pharmacokinetics compared to mammals make silkworm infection model suitable to examine the therapeutic effectiveness of antimicrobial agents. Based on this, we utilized silkworm bacterial infection model to screen the therapeutic effectiveness of various microbial culture broths and successfully identified a therapeutically effective novel antibiotic, lysocin E, which has a novel mode of action of binding to menaquinone, thus leading to membrane damage and bactericidal activity. The similar approach to screen potential antibiotics resulted in the identification of other therapeutically effective novel antibiotics, such as nosokomycin and ASP2397 (VL-2397). In this regard, we propose that the silkworm antibiotic screening model is very effective for identifying novel antibiotics. In this review, we summarize the advantages of the silkworm model and propose that the utilization of silkworm infection model will facilitate the discovery of novel therapeutically effective antimicrobial agents.
对抗多药耐药病原体全球传播的新型抗生素需求持续增长。导致人类致命感染的致病细菌和真菌也会杀死家蚕,而感染的家蚕可用临床治疗感染所用的相同抗生素治愈。作为一种无脊椎动物模型,家蚕模型具有方便、成本低、无伦理问题的特点。与哺乳动物相比,家蚕具有保守的免疫反应和相似的药代动力学,这使得家蚕感染模型适合用于检验抗菌剂的治疗效果。基于此,我们利用家蚕细菌感染模型筛选各种微生物培养液的治疗效果,并成功鉴定出一种具有治疗效果的新型抗生素——溶菌素E,它具有与甲萘醌结合的新型作用模式,从而导致膜损伤和杀菌活性。采用类似方法筛选潜在抗生素,还鉴定出了其他具有治疗效果的新型抗生素,如诺索霉素和ASP2397(VL - 2397)。在这方面,我们认为家蚕抗生素筛选模型在鉴定新型抗生素方面非常有效。在本综述中,我们总结了家蚕模型的优势,并提出利用家蚕感染模型将有助于发现新型治疗有效的抗菌剂。