Journal
NATURE CHEMICAL BIOLOGY
Volume 11, Issue 2, Pages 127-U68Publisher
NATURE PORTFOLIO
DOI: 10.1038/NCHEMBIO.1710
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Funding
- Genome Pharmaceuticals Institute Co., Ltd.
- Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO)
- Japan Society for the Promotion of Science (JSPS) [24689008, 25460036]
- MEXT [24102510, 26102714]
- JSPS [24-11042]
- Japan Science and Technology Agency (JST)
- Grants-in-Aid for Scientific Research [13F03093, 12J11042, 26253003, 24102510, 25460036, 26102714, 24689008] Funding Source: KAKEN
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To obtain therapeutically effective new antibiotics, we first searched for bacterial culture supernatants with antimicrobial activity in vitro and then performed a secondary screening using the silkworm infection model. Through further purification of the in vivo activity, we obtained a compound with a previously uncharacterized structure and named it 'lysocin E'. Lysocin E interacted with menaquinone in the bacterial membrane to achieve its potent bactericidal activity, a mode of action distinct from that of any other known antibiotic, indicating that lysocin E comprises a new class of antibiotic. This is to our knowledge the first report of a direct interaction between a small chemical compound and menaquinone that leads to bacterial killing. Furthermore, lysocin E decreased the mortality of infected mice. To our knowledge, lysocin E is the first compound identified and purified by quantitative measurement of therapeutic effects in an invertebrate infection model that exhibits robust in vivo effects in mammals.
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