Discovery of a new antifungal agent ASP2397 using a silkworm model of Aspergillus fumigatus infection
| Autor: | Kazuhisa Sekimizu, Hiroshi Hamamoto, Ryuichi Kanasaki, Koji Yoshikawa, Shigetada Furukawa, Ikuko Nakamura, Akihiko Fujie |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Drug Antifungal Agents medicine.drug_class Antiparasitic media_common.quotation_subject 030106 microbiology Antibiotics Aspergillosis Peptides Cyclic Aspergillus fumigatus Microbiology 03 medical and health sciences chemistry.chemical_compound Mice In vivo Coordination Complexes Drug Discovery medicine Animals media_common Pharmacology Mice Inbred ICR Natural product biology fungi medicine.disease biology.organism_classification Bombyx Glycopeptide Survival Rate Disease Models Animal chemistry Female |
| Zdroj: | The Journal of antibiotics. 70(1) |
| ISSN: | 1881-1469 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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