Cryptic antifungal compounds active by synergism with polyene antibiotics.
The majority of antifungal compounds reported so far target the cell wall or cell membrane of fungi, suggesting that other types of antibiotics cannot exert their activity because they cannot penetrate into the cells. Therefore, if the permeability of the cell membrane could be enhanced, many antibiotics might be found to have antifungal activity. We here used the polyene antibiotic nystatin, which binds to ergosterol and forms pores at the cell membrane, to enhance the cellular permeability. In the presence of nystatin, many culture extracts from entomopathogenic fungi displayed antifungal activity. Among all the active extracts, two active components were purified and identified as helvolic acid and terramide A. Because the minimum inhibitory concentration of either compound was reduced four-fold in the presence of nystatin, it can be concluded that this screening method is useful for detecting novel antifungal activity.
International Center for Biotechnology, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Hiroshi
H
Kinoshita
International Center for Biotechnology, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Mariko
M
Yoshioka
National Institute of Fruit Tree Science, 2-1 Fujimoto, Tsukuba, Ibaraki 305-8605, Japan.
Fumio
F
Ihara
International Center for Biotechnology, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan; MU-OU Collaborative Research Center for Bioscience and Biotechnology, Faculty of Science, Mahidol University, Rama VI Rd., Bangkok 10400, Thailand. Electronic address: nihira@icb.osaka-u.ac.jp.
Takuya
T
Nihira
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D054659:Diketopiperazines / Q000302:isolation & purification / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004357:Drug Synergism; D004875:Ergosterol / Q000737:chemistry; D005658:Fungi / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D005672:Fusidic Acid / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000494:pharmacology; D007769:Lactams / Q000302:isolation & purification / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009761:Nystatin / Q000737:chemistry / Q000494:pharmacology*; D011090:Polyenes / Q000737:chemistry / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D054659:Diketopiperazines; D007769:Lactams; D011090:Polyenes; C000611077:terramide A; D009761:Nystatin; D005672:Fusidic Acid; C011267:helvolic acid; D004875:Ergosterol
Antifungal compounds; Entomopathogenic fungi; Helvolic acid; Polyene antibiotics; Terramide A