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.
Highlights
The conventional approach of antibiotic discovery includes purification from culture supernatants of soil bacteria by monitoring in vitro antimicrobial activity
From an anatomic point of view, B. mori harbors most of the organs and systems present in mammals, leading scientists to use B. mori as an excellent model organism to elucidate various processes in life sciences, which has been facilitated by the availability of its complete genome sequence and the development of technologies for genetic manipulation
We have previously shown that pathogenic bacteria and fungi that cause fatal infections in human beings such as methicillin sensitive and resistant Staphylococcus aureus; Pseudomonas aeruginosa can kill silkworms
Summary
The conventional approach of antibiotic discovery includes purification from culture supernatants of soil bacteria by monitoring in vitro antimicrobial activity. This approach makes it difficult to identify novel antibiotics, due to the frequent isolation of overlapping chemical entities. Only a small fraction of the antibiotics isolated using this approach exert therapeutic activity in animal models, which further limits the discovery of the therapeutically effective antibiotic. The conventional approach of antibiotic screening clearly requires remodeling. To overcome the problems associated with conventional screening methods, we used the silkworm as an animal model to evaluate the therapeutic effects of candidate samples. We discuss the advantages of the silkworm model for antimicrobial drug development
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