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Antimicrobial Agents and Chemotherapy, August 1999, p. 1993-1999, Vol. 43, No. 8
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Unusual Antimicrotubule Activity of the Antifungal Agent Spongistatin 1

Yulia Y. Ovechkina,1 Robin K. Pettit,2 Zbigniew A. Cichacz,2 George R. Pettit,2 and Berl R. Oakley1,*

Department of Molecular Genetics, The Ohio State University, Columbus, Ohio 43210,1 and Departments of Microbiology and Chemistry, Cancer Research Institute, Arizona State University, Tempe Arizona 852872

Received 22 March 1999/Returned for modification 28 April 1999/Accepted 7 June 1999

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 µg/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.

* Corresponding author. Mailing address: Department of Molecular Genetics, The Ohio State University, 484 W. 12th Ave., Columbus, OH 43210. Phone: (614) 292-3472. Fax: (614) 292-4466. E-mail: Oakley.2{at}OSU.EDU.

Antimicrobial Agents and Chemotherapy, August 1999, p. 1993-1999, Vol. 43, No. 8
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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