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: ジャーナルへの寄稿記事

75 引用 (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.

元の言語英語
ページ(範囲)127-133
ページ数7
ジャーナルNature Chemical Biology
11
発行部数2
DOI
出版物ステータス出版済み - 2 1 2015

Fingerprint

Vitamin K 2
Anti-Bacterial Agents
Membranes
Bombyx
Therapeutic Uses
Invertebrates
Infection
Mammals
lysocin E
Mortality

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

これを引用

Hamamoto, H., Urai, M., Ishii, K., Yasukawa, J., Paudel, A., Murai, M., ... Sekimizu, K. (2015). Lysocin e is a new antibiotic that targets menaquinone in the bacterial membrane. Nature Chemical Biology, 11(2), 127-133. https://doi.org/10.1038/nchembio.1710

Lysocin e is a new antibiotic that targets menaquinone in the bacterial membrane. / Hamamoto, Hiroshi; Urai, Makoto; Ishii, Kenichi; Yasukawa, Jyunichiro; Paudel, Atmika; Murai, Motoki; Kaji, Takuya; Kuranaga, Takefumi; Hamase, Kenji; Katsu, Takashi; Su, Jie; Adachi, Tatsuo; Uchida, Ryuji; Tomoda, Hiroshi; Yamada, Maki; Souma, Manabu; Kurihara, Hiroki; Inoue, Masayuki; Sekimizu, Kazuhisa.

:: Nature Chemical Biology, 巻 11, 番号 2, 01.02.2015, p. 127-133.

研究成果: ジャーナルへの寄稿記事

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 2015, 'Lysocin e is a new antibiotic that targets menaquinone in the bacterial membrane', Nature Chemical Biology, 巻. 11, 番号 2, pp. 127-133. https://doi.org/10.1038/nchembio.1710
Hamamoto H, Urai M, Ishii K, Yasukawa J, Paudel A, Murai M その他. Lysocin e is a new antibiotic that targets menaquinone in the bacterial membrane. Nature Chemical Biology. 2015 2 1;11(2):127-133. https://doi.org/10.1038/nchembio.1710
Hamamoto, Hiroshi ; Urai, Makoto ; Ishii, Kenichi ; Yasukawa, Jyunichiro ; Paudel, Atmika ; Murai, Motoki ; Kaji, Takuya ; Kuranaga, Takefumi ; Hamase, Kenji ; Katsu, Takashi ; Su, Jie ; Adachi, Tatsuo ; Uchida, Ryuji ; Tomoda, Hiroshi ; Yamada, Maki ; Souma, Manabu ; Kurihara, Hiroki ; Inoue, Masayuki ; Sekimizu, Kazuhisa. / Lysocin e is a new antibiotic that targets menaquinone in the bacterial membrane. :: Nature Chemical Biology. 2015 ; 巻 11, 番号 2. pp. 127-133.
@article{0e6ab92ebbc34c2b9e482916277e3888,
title = "Lysocin e is a new antibiotic that targets menaquinone in the bacterial membrane",
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.",
author = "Hiroshi Hamamoto and Makoto Urai and Kenichi Ishii and Jyunichiro Yasukawa and Atmika Paudel and Motoki Murai and Takuya Kaji and Takefumi Kuranaga and Kenji Hamase and Takashi Katsu and Jie Su and Tatsuo Adachi and Ryuji Uchida and Hiroshi Tomoda and Maki Yamada and Manabu Souma and Hiroki Kurihara and Masayuki Inoue and Kazuhisa Sekimizu",
year = "2015",
month = "2",
day = "1",
doi = "10.1038/nchembio.1710",
language = "English",
volume = "11",
pages = "127--133",
journal = "Nature Chemical Biology",
issn = "1552-4450",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Lysocin e is a new antibiotic that targets menaquinone in the bacterial membrane

AU - Hamamoto, Hiroshi

AU - Urai, Makoto

AU - Ishii, Kenichi

AU - Yasukawa, Jyunichiro

AU - Paudel, Atmika

AU - Murai, Motoki

AU - Kaji, Takuya

AU - Kuranaga, Takefumi

AU - Hamase, Kenji

AU - Katsu, Takashi

AU - Su, Jie

AU - Adachi, Tatsuo

AU - Uchida, Ryuji

AU - Tomoda, Hiroshi

AU - Yamada, Maki

AU - Souma, Manabu

AU - Kurihara, Hiroki

AU - Inoue, Masayuki

AU - Sekimizu, Kazuhisa

PY - 2015/2/1

Y1 - 2015/2/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84928046813&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928046813&partnerID=8YFLogxK

U2 - 10.1038/nchembio.1710

DO - 10.1038/nchembio.1710

M3 - Article

C2 - 25485686

AN - SCOPUS:84928046813

VL - 11

SP - 127

EP - 133

JO - Nature Chemical Biology

JF - Nature Chemical Biology

SN - 1552-4450

IS - 2

ER -