Lysocin E is a new antibiotic that targets menaquinone in the bacterial membrane
| Autor: | Takefumi Kuranaga, Kenji Hamase, Kenichi Ishii, Tatsuo Adachi, Masayuki Inoue, Manabu Souma, Jyunichiro Yasukawa, Atmika Paudel, Makoto Urai, Motoki Murai, Hiroshi Tomoda, Hiroki Kurihara, Jie Su, Hiroshi Hamamoto, Takashi Katsu, Ryuji Uchida, Maki K. Yamada, Takuya Kaji, Kazuhisa Sekimizu |
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| Rok vydání: | 2014 |
| Předmět: |
Staphylococcus aureus
medicine.drug_class Gram-positive bacteria Phenotypic screening Antibiotics Microbial Sensitivity Tests Gram-Positive Bacteria medicine.disease_cause Peptides Cyclic Membrane Potentials Microbiology Mice Bacteriolysis Bacterial Proteins In vivo Drug Discovery medicine Animals Molecular Biology Mice Inbred ICR Molecular Structure biology Cell Membrane Vitamin K 2 Cell Biology Staphylococcal Infections Bombyx biology.organism_classification Antimicrobial In vitro Anti-Bacterial Agents Disease Models Animal Lysobacter Bacteria |
| Zdroj: | Nature Chemical Biology. 11:127-133 |
| ISSN: | 1552-4469 1552-4450 |
| DOI: | 10.1038/nchembio.1710 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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