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.
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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 -