Fungicidal action of aureobasidin A, a cyclic depsipeptide antifungal antibiotic, against Saccharomyces cerevisiae

Abstract

Aureobasidin A, an antifungal antibiotic inhibiting a wide range of pathogenic fungi, is lethal for growing cells of susceptible fungi. We did cytological studies on the mechanism of its fungicidal action against Saccharomyces cerevisiae. When cultures were treated with 5.0 micrograms of aureobasidin A per ml, the numbers of viable cells started to decrease after 2 to 3 h of incubation, and most cells had lost viability after 5 to 6 h. When cell death in the treated cultures began, amino acids released by the cells could be detected, indicating disruption of the cell membrane. The proportion of cells with a single small bud or two or more buds increased as the population of viable cells decreased. Most such cells had the DNA content of cells in the G2 phase of the cell cycle, suggesting that the drug inhibited some cellular process involved in normal bud growth but did not affect DNA replication. Disruption of actin assembly was found in many cells treated for 2 to 3 h, as was chitin delocalization. The results suggest that aureobasidin A has a previously unknown mechanism of fungicidal action toward S. cerevisiae. It causes aberrant actin assembly, inhibiting the normal budding process and leading to cell death, probably through destruction of membrane integrity.

Antifungal activity and mode of action of silver nano-particles on Candida albicans

“…These data suggest that nano-Ag inhibited some cellular processes which are involved in normal bud growth. Endo et al have reported that the inhibition of bud growth correlates with membrane damage (Endo et al 1997). This report suggests that nano-Ag inhibits the normal budding process, probably through the destruction of membrane integrity.…”

Sphingolipid biosynthesis is required for polar growth in the dimorphic phytopathogen Ustilago maydis

“…However, in A. nidulans and S. cerevisiae treatment with AbA caused cell cycle arrest and inhibition of polar growth. The cell cycle arrest was associated with the accumulation of ceramides produced after the inhibition of the IPC synthase (Cheng et al, 2003;Endo et al, 1997). Then, either AbA treatment of U. maydis cells does not result in ceramide accumulation to sufficient levels to arrest cell cycle or ceramide accumulation does not cause cell cycle arrest in this organism.…”

“…In A. nidulans and S. cerevisiae inhibition of IPC synthase by treatment with AbA results in cell cycle arrest, most likely as a consequence of ceramide accumulation (Cheng et al, 2003;Endo et al, 1997). U. maydis poses a special case since it naturally arrests its cell cycle at G2 during b-dependent filamentation.…”

“…AbA is highly active against many animal pathogenic fungi including C. albicans, C. neoformans, Histoplasma capsulatum and Blastomyces dermatitidis (Takesako et al, 1993), and also some protozoa and plants (Bromley et al, 2003;Denny et al, 2006;Sonda et al, 2005;Suzuki et al, 2008). Several studies using AbA to block sphingolipid synthesis indicated that the absence of sphingolipids affect cell morphogenesis and polarized hyphal growth (Cheng et al, 2001;Endo et al, 1997;Hashida-Okado et al, 1998). It is thought that these effects are mediated by interfering with the formation of SRDs.…”

“…It is thought that these effects are mediated by interfering with the formation of SRDs. However, both in A. nidulans and in S. cerevisiae inhibition of the IPC synthase by treatment with AbA also results in cell cycle arrest at G1 or G2, respectively, most likely as a consequence of ceramide accumulation (Cheng et al, 2001;Endo et al, 1997).…”