Advantages of the Silkworm As an Animal Model for Developing Novel Antimicrobial Agents
Suresh Panthee1, Atmika Paudel1, Hiroshi Hamamoto1
1Institute of Medical Mycology, Teikyo University Tokyo, Japan.
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.
Insights
The silkworm infection model effectively screens for novel antibiotics. This invertebrate model aids in discovering new antimicrobial agents like lysocin E, crucial for combating drug-resistant pathogens.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Growing demand for novel antibiotics due to multi-drug resistant pathogens.
- Silkworms are susceptible to human pathogens and can be treated with clinical antibiotics.
- Silkworm models offer a convenient, low-cost, and ethically sound alternative for antimicrobial research.
Purpose of the Study:
- To evaluate the efficacy of the silkworm infection model for screening novel antibiotics.
- To identify new antimicrobial agents effective against drug-resistant bacteria and fungi.
Main Methods:
- Utilized a silkworm bacterial infection model to screen microbial culture broths.
- Assessed the therapeutic effectiveness of various antimicrobial agents in infected silkworms.
Main Results:
- Successfully identified the novel antibiotic lysocin E with a unique mechanism of action (menaquinone binding, membrane damage).
- Identified other novel antibiotics, including nosokomycin and ASP2397 (VL-2397), using the same screening approach.
- Demonstrated the silkworm model's effectiveness in discovering therapeutically potent antibiotics.
Conclusions:
- The silkworm infection model is a highly effective platform for discovering novel antibiotics.
- This model facilitates the identification of antimicrobial agents with novel mechanisms of action.
- Further utilization of the silkworm model can accelerate the discovery of new treatments for infectious diseases.
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