RRC ID 33150
著者 Hamamoto H, Urai M, Ishii K, Yasukawa J, Paudel A, Murai M, Kaji T, Kuranaga T, Hamase K, Katsu T, Su J, Adachi T, Uchida R, Tomoda H, Yamada M, Souma M, Kurihara H, Inoue M, Sekimizu K.
タイトル Lysocin E is a new antibiotic that targets menaquinone in the bacterial membrane.
ジャーナル Nat Chem Biol
Abstract 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.
巻・号 11(2)
ページ 127-33
公開日 2015-2-1
DOI 10.1038/nchembio.1710
PII nchembio.1710
PMID 25485686
MeSH Animals Anti-Bacterial Agents / isolation & purification Anti-Bacterial Agents / pharmacology* Anti-Bacterial Agents / therapeutic use Bacterial Proteins / genetics Bacterial Proteins / metabolism Bacteriolysis / drug effects Bombyx / microbiology Cell Membrane / drug effects* Cell Membrane / metabolism Disease Models, Animal Drug Discovery / methods* Gram-Positive Bacteria / drug effects* Gram-Positive Bacteria / genetics Gram-Positive Bacteria / metabolism Lysobacter / metabolism Membrane Potentials / drug effects Mice Mice, Inbred ICR Microbial Sensitivity Tests Molecular Structure Peptides, Cyclic / isolation & purification Peptides, Cyclic / pharmacology* Peptides, Cyclic / therapeutic use Staphylococcal Infections / drug therapy Staphylococcus aureus / drug effects Staphylococcus aureus / genetics Staphylococcus aureus / metabolism Vitamin K 2 / antagonists & inhibitors* Vitamin K 2 / metabolism
IF 12.587
引用数 88
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
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