Development of antibiotics using silkworm bacteria and fungi infection model

Abstract

The emergence of antimicrobial resistant (AMR) bacteria has become a serious threat to public health. It is important that we ˆnd a mechanistically novel antibiotic to combat AMR. However, ˆnding compounds which are both therapeutically eŠective and safe is difficult in the development of antibiotics. To solve these problems, we have focused on the silkworm model, which is economical and poses fewer ethical issues, as a means to evaluate the therapeutic eŠec-tiveness of test compounds in early stages of antibiotic development. Actually, the silkworm has pharmacokinetic parameters similar to mammals, and we revealed that antibiotics showed ED50 s consistent with mammalian models. Thus, we screened therapeutically eŠective samples from natural products using the silkworm model, and found 23 candidates out of 15000 samples. We ultimately identiˆed a novel antibiotic, lysocin E, and found that it demonstrates a potent therapeutic eŠect in the mouse systemic infection model. Furthermore, since the target of lysocin E is menaquinone on the bacterial membrane, it belongs to a novel class of antibiotics. In addition, we found a novel antibacterial agent named nosokomycin, GPI0363, and an antifungal agent, VL-2397 (ASP2397), using the silkworm model. In this report, we introduce the usefulness of the silkworm model in the development of antibiotics.