Advantages of the Silkworm As an Animal Model for Developing Novel Antimicrobial Agents

Abstract

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.

Polysaccharides of a fermented food, natto, suppress sucrose-induced hyperglycemia in an <i>in vivo</i> evaluation system and inhibit glucose uptake by human intestinal cells

“…Experiments using the silkworm evaluation system revealed that the viscous component of natto has a suppressive effect against sucrose-and glucose-induced hyperglycemia. Silkworms are useful for large-scale in vivo evaluation because they are inexpensive and can be reared in large groups (21)(22)(23)(24)(25)(26)(27). We reported the discovery of several active substances that suppress postprandial hyperglycemia using the silkworm evaluation system (4,11,28).…”

Antimicrobial peptides fromBombyx mori: a splendid immune defense response in silkworms

“…91 The literature revealed that AMPs are a key component for immune defense against bacterial infection in silkworm. 7,87,[92][93][94][95][96] These observations stipulate that production of AMPs in silkworm through the Toll and IMD pathway is absolutely critical and remains unresolved. Hence, there is a need for detailed studies to understand such mechanisms, which will aid in providing more powerful tools against pathogenic multi-drugresistant microbes.…”

GPI0363 inhibits the interaction of RNA polymerase with DNA inStaphylococcus aureus

“…1a), identied by screening in a silkworm infection model. 8,9 It inhibited transcription in Staphylococcus aureus by binding to the primary sigma factor, SigA, and a single point mutation (D201N) in SigA was responsible for resistance to GPI0363. 8 However, the mechanism of how it inhibits transcription was not fully understood.…”