title: Unusual antimicrotubule activity of the antifungal agent spongistatin 1.
abstract: Spongistatin 1, a macrocyclic lactone from the marine sponge Hyrtios erecta, has broad-spectrum antifungal activity. Since this compound is a potent antimicrotubule agent in mammalian cells, we examined its effects on the filamentous fungus Aspergillus nidulans to determine if its antifungal effects are due to antimicrotubule activity. At 25 microg/ml (twice the MIC), spongistatin 1 caused a greater-than-twofold elevation of the chromosome and spindle mitotic indices. Immunofluorescence microscopy revealed that mitotic spindles were smaller and shorter than in control germlings. However, late-anaphase and telophase nuclei were seen occasionally, and this suggests that the spindles are capable of segregating chromosomes. Spongistatin 1 had more dramatic effects on cytoplasmic microtubules. At 30 min after initiation of treatment, 83% of germlings contained fragmented microtubules and after 2 h of treatment, microtubules had disappeared completely from 82% of germlings. In contrast, microtubules disappeared rapidly and completely from germlings treated with benomyl. We conclude that spongistatin 1 has antimicrotubule activity in A. nidulans and that its mechanism of action may involve a novel microtubule-severing activity.
authors.affiliation: Department of Molecular Genetics, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Ovechkina
authors.forename: R K
authors.initials: RK
authors.lastname: Pettit
authors.forename: Z A
authors.initials: ZA
authors.lastname: Cichacz
authors.forename: G R
authors.initials: GR
authors.lastname: Pettit
authors.forename: B R
authors.initials: BR
authors.lastname: Oakley
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001233:Aspergillus nidulans / Q000187:drug effects; D001542:Benomyl / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005659:Fungicides, Industrial / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology*; D018942:Macrolides; D008826:Microbial Sensitivity Tests; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000187:drug effects*; D008940:Mitotic Index / Q000187:drug effects; D000095702:Polyether Toxins
chemical_list: D000935:Antifungal Agents; D001542:Benomyl; D004988:Ethers, Cyclic; D005659:Fungicides, Industrial; D007783:Lactones; D018942:Macrolides; C083856:spongistatin 1; D000095702:Polyether Toxins