title: Discovery of a new antifungal agent ASP2397 using a silkworm model of Aspergillus fumigatus infection.
abstract: Natural products are the major source of currently available drugs. However, screening natural product presents several challenges, including the time-consuming and labor-intensive steps required for the isolation of a drug from crude extracts as well as the differences between the activities of compounds in vitro and in vivo. To address these challenges, we used silkworm larvae infected with Aspergillus fumigatus to screen a natural products library for potent drugs to treat invasive aspergillosis. A rationally designed library was constructed using numerous, geographically diverse fungal species and then screened to collect extracts of microorganisms that had detectable anti-Aspergillus activity. We evaluated this library using cultures of A. fumigatus and a silkworm model system of A. fumigatus infection. With this model, we identified the novel antifungal compound ASP2397 that not only cured infected silkworm larvae but also increased the rates of survival of mice infected with A. fumigatus. These findings strongly support the utility of the silkworm screening system for the simple and rapid isolation of antibiotics from natural products libraries.
authors: Drug Discovery Research, Astellas Pharma Inc., Ibaraki, Japan.
authors: Ikuko
authors: I
authors: Nakamura
authors: Drug Discovery Research, Astellas Pharma Inc., Ibaraki, Japan.
authors: Ryuichi
authors: R
authors: Kanasaki
authors: Drug Discovery Research, Astellas Pharma Inc., Ibaraki, Japan.
authors: Koji
authors: K
authors: Yoshikawa
authors: Drug Discovery Research, Astellas Pharma Inc., Ibaraki, Japan.
authors: Shigetada
authors: S
authors: Furukawa
authors: Drug Discovery Research, Astellas Pharma Inc., Ibaraki, Japan.
authors: Akihiko
authors: A
authors: Fujie
authors: Teikyo University Institute of Medical Mycology, Tokyo, Japan.
authors: Hiroshi
authors: H
authors: Hamamoto
authors: Teikyo University Institute of Medical Mycology, Tokyo, Japan.|Genome Pharmaceuticals Institute, Tokyo, Japan.
authors: Kazuhisa
authors: K
authors: Sekimizu
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects*; D012831:Bombyx; D056831:Coordination Complexes / Q000494:pharmacology*; D004195:Disease Models, Animal; D055808:Drug Discovery / Q000379:methods; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D010456:Peptides, Cyclic / Q000494:pharmacology*; D015996:Survival Rate
chemical_list: D000935:Antifungal Agents; D056831:Coordination Complexes; D010456:Peptides, Cyclic; C000611448:VL-2397