Spongistatin 1, a macrocyclic lactone from the marine sponge Hyrtios erecta
, has broad-spectrum antifungal activity. Since this compound is a potent a
ntimicrotubule agent in mammalian cells, we examined its effects on the fil
amentous fungus Aspergillus nidulans to determine if its antifungal effects
are due to antimicrotubule activity, At 25 mu g/ml (twice the MIC), spongi
statin 1 caused a greater-than-twofold elevation of the chromosome and spin
dle mitotic indices. Immunofluorescence microscopy revealed that mitotic sp
indles were smaller and shorter than in control germlings, However, late-an
aphase and telophase nuclei were seen occasionally, and this suggests that
the spindles are capable of segregating chromosomes. Spongistatin 1 had mor
e 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 germl
ings. In contrast, microtubules disappeared rapidly and completely from ger
mlings treated with benomyl, We conclude that spongistatin 1 has antimicrot
ubule activity in A. nidulans and that its mechanism of action may involve
a novel microtubule-severing activity.