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Silkworm model of bacterial infection facilitates the identification of lysocin E, a potent, ultra-rapid bactericidal antibiotic

The Journal of Antibiotics (2024)Cite this article

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Abstract

The development of novel antimicrobial agents is required to solve the problem of antimicrobial resistance. We established a quantitative method for evaluating the therapeutic efficacy of antimicrobial agents in a silkworm bacterial infection model. Pharmacokinetic factors are present in the silkworm as well as in mice, and evaluating the therapeutic efficacy of antimicrobial agents is possible in a silkworm infection model, comparable to that in a mammalian model. This silkworm model was used to screen for novel antimicrobial agents with therapeutic efficacy as an indicator. As a result, a new antibiotic, lysocin E, was discovered. Lysocin E has a completely different mechanism of action from existing antimicrobial agents, and its potent bactericidal activity leads to remarkable therapeutic efficacy in a mouse model. In this review, I describe the features of the silkworm model that have contributed to the discovery of lysocin E and its mechanisms of action.

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Acknowledgements

I extend my heartfelt gratitude to Professor Emeritus Hiroshi Tomoda of Kitasato University for receiving the Sumiki-Umezawa Memorial Award in 2023 from the Japan Antibiotics Research Association. I also want to express my sincere appreciation to my mentor, Professor Emeritus Kazuhisa Sekimizu of the University of Tokyo. Furthermore, I am thankful to numerous researchers and students who contributed significantly to this research. Special acknowledgment goes to Professor Emeritus Hideo Yamaguchi of Teikyo University for his invaluable suggestions for the development of drugs for infectious diseases.

Funding

This work was supported partly by the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO), Japan Science and Technology Agency (JST) A-STEP (High-Risk Challenging Type), Drug Discovery Support Promotion Project from AMED: Japan Agency for Medical Research and Development, JSPS KAKENHI (Grant No. 24689008, 26102714, 15H05783, 19K07140, 23H02719) the Mochida Memorial Foundation for Medical and Pharmaceutical Research, the Takeda Science Foundation, the Institute for Fermentation, Osaka.

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  1. Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan

    Hiroshi Hamamoto

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Correspondence to Hiroshi Hamamoto.

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Hiroshi Hamamoto was awarded the Sumiki-Umezawa Memorial Award from the Japan Antibiotics Research Association in 2022. This review article is partly based on his award-winning research.

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Hamamoto, H. Silkworm model of bacterial infection facilitates the identification of lysocin E, a potent, ultra-rapid bactericidal antibiotic. J Antibiot (2024). https://doi.org/10.1038/s41429-024-00739-x

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