Lysocin e is a new antibiotic that targets menaquinone in the bacterial membrane

Hiroshi Hamamoto, Makoto Urai, Kenichi Ishii, Jyunichiro Yasukawa, Atmika Paudel, Motoki Murai, Takuya Kaji, Takefumi Kuranaga, Kenji Hamase, Takashi Katsu, Jie Su, Tatsuo Adachi, Ryuji Uchida, Hiroshi Tomoda, Maki Yamada, Manabu Souma, Hiroki Kurihara, Masayuki Inoue, Kazuhisa Sekimizu

研究成果: Contribution to journalArticle査読

96 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)127-133
ページ数7
ジャーナルNature Chemical Biology
11
2
DOI
出版ステータス出版済み - 2 1 2015

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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