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      Unusual Antimicrotubule Activity of the Antifungal Agent Spongistatin 1

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      Antimicrobial Agents and Chemotherapy

      American Society for Microbiology

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          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 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.

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          Author and article information

          Journal
          Antimicrobial Agents and Chemotherapy
          Antimicrob. Agents Chemother.
          American Society for Microbiology
          0066-4804
          1098-6596
          August 01 1999
          August 01 1999
          August 01 1999
          August 01 1999
          : 43
          : 8
          : 1993-1999
          Article
          10.1128/AAC.43.8.1993
          © 1999
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