2014
DOI: 10.1038/nchembio.1710
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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 … Show more

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Cited by 212 publications
(235 citation statements)
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“…RH2180-5, using a silkworm model of infection (3). Injection of yeast β-glucans and bacterial peptidoglycans into the silkworm Bombyx mori induces maturation of the insect cytokine paralytic peptide, which results in muscle contraction of the larvae (4,5).…”
Section: Introductionmentioning
confidence: 99%
“…RH2180-5, using a silkworm model of infection (3). Injection of yeast β-glucans and bacterial peptidoglycans into the silkworm Bombyx mori induces maturation of the insect cytokine paralytic peptide, which results in muscle contraction of the larvae (4,5).…”
Section: Introductionmentioning
confidence: 99%
“…Furthermore, the vinylsulfonamide 86, which was designed as mimic of O-succinylbenzoate-CoA ester was reported to efficiently inhibit MenE at low nanomolar concentrations (Lu et al 2012). Recently, the novel natural cyclodepsipeptide lysocin E 87 (Scheme 28) was reported to target the redox metabolism in bacteria by directly binding to menaquinone (Hamamoto et al 2014). Since the biosynthesis of menaquinone is a multi-enzymatic pathway as described above and the role of menaquinone is crucial for viability of bacteria, menaquinone seems to be a much smarter choice for an antibacterial target than the individual enzymes of the biosynthesis, even more when considering that an alternative biosynthetic pathway for menaquinones starting from futalosine exists in several Gram-positive bacteria.…”
Section: Menaquinone As a Small Molecule Antibacterial Targetmentioning
confidence: 99%
“…In this assay, candidate compounds or test samples are injected into pathogenic microorganism-infected silkworm larvae and the survival rate over a few days is then evaluated. In a silkworm infection model with methicillin-resistant Staphylococcus aureus (MRSA), nosokomycins (2)(3)(4), and lysocins in bacterial culture broths were identified as effective in vivo anti-MRSA antibiotics (1).…”
Section: Introductionmentioning
confidence: 99%
“…To overcome these issues, an in vivo-mimic infection assay using the silkworm has been introduced to screening at the early stage and is expected to be a relevant strategy for the discovery of therapeutically effective candidates (1). In this assay, candidate compounds or test samples are injected into pathogenic microorganism-infected silkworm larvae and the survival rate over a few days is then evaluated.…”
Section: Introductionmentioning
confidence: 99%