On the mechanism of action of the myxobacterial fungicide ambruticin

The myxobacterial fungicide, ambruticin, kills the yeast, Hansenula anomala, with high efficacy (MIC 0.05 mug/ml), but only when the cells are growing. The earliest effect, observed almost immediately after the addition of the antibiotic, is a transient but substantial increase of intracellular glycerol, followed by an accumulation of triacylglycerols and free fatty acids. At about the time when free fatty acids accumulate, the cells become leaky to low molecular weight compounds. We assume that this leakage kills the cells. The mechanism of action of ambruticin thus appears to be the same as that of the phenylpyrroles, e.g., pyrrolnitrin, viz., interference with osmoregulation.