Targeted yeast vacuole disruption by polyene antibiotics with a macrocyclic lactone ring

In this study, the polyene macrolide antibiotics amphotericin B (AmB), nystatin and filipin III were evaluated for their fungicidal activity and their ability to produce vacuole disruption as well as enhancement of these activities by allicin using Saccharomyces cerevisiae. Nystatin has a macrocyclic lactone ring analogous to AmB and their fungicidal activities were both increased by allicin, an allyl-sulfur compound, whereas filipin III, a pentaene macrolide, did not show an increase in fungicidal activity in the presence of allicin. Vacuole staining with the fluorescent probe FM4-64 showed that both AmB and nystatin induced vacuole membrane disintegration at their lethal concentrations; in addition, the vacuole disruptive effect was also enhanced by allicin. In contrast, filipin III did not affect vacuole morphology and addition of allicin had no effect despite filipin III localising to the cell cytoplasm. Isolated S. cerevisiae vacuoles were disrupted following treatment both with nystatin and AmB, though this activity was not potentiated in the presence of allicin. In contrast, filipin III had little effect on the vacuole architecture. This study reveals differential effects of polyene antibiotics on vacuoles in S. cerevisiae, which may be due to differences in the structure of the macrocyclic ring.