Lysocin E is a New Antibiotic That Targets Menaquinone in the Bacterial Membrane

Overview

Journal Nat Chem Biol

Specialties Biochemistry
Biology
Chemistry

Date 2014 Dec 9

PMID 25485686

Citations 87

Authors

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

Affiliations

Soon will be listed here.

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.

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