Spongistatin 1, a macrocyclic lactone polyether from the marine sponge Hyrtios erecta, was fungicidal for a variety of opportunistic yeasts and filamentous fungi, including strains resistant to amphotericin B, ketoconazole and flucytosine. In broth macrodilution assays, MICs ranged from 0.195 to 12.5 μg/ml, and minimum fungicidal concentrations ranged from 3.12 to 25 μg/ml. Initial disk diffusion screens with six related macrocyclic lactone polyethers from H. erecta and Spirastrella spinispirulifera, revealed that these polyethers were also antifungal. The fungicidal activity of spongistatin 1 was confirmed in killing kinetics studies, where killing of Candida albicans and Cryptococcus neoformans occurred within 6 and 12 h, respectively. During the killing kinetics experiments, non-treated C. albicans maintained the yeast morphology. However, elongated forms resembling germ tubes were the predominant morphologic form in spongistatin 1-treated C. albicans cultures. The spongistatins show promise as potential antifungal agents and as probes to study fungal morphogenesis and nuclear division.
Bibliographical noteFunding Information:
With appreciation we acknowledge the financial assistance provided by a Western Oregon State College Foundation grant, Outstanding Investigator Grant CA44344-01-09 awarded by the Division of Cancer Treatment, the US National Cancer Institute, DHHS, The Arizona Disease Control Research Commission and the Fannie E. Rippel Foundation. We thank Melanie Filiatrault for performing the disk diffusion assays.
- Antifungal susceptibility
- Opportunistic fungi