Mode of Action of the Antimycotic Agent G2 Isolated from Alfalfa Roots

Itzhack Polacheck*, Mordekhai Levy, Miriam Guizie, Uri Zehavi, Michael Naim, Ruth Evron

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The mode of action of the antimycotic alfalfa root saponin, medicagenic acid 3-0-β-Dglucopyranoside (compound G2), which possesses a pronounced antifungal activity against medically important yeasts and dermatophytes, was studied in Saccharomyces cerevisiae. Compound G2 caused lethal leakage of ions out of the yeast cells. Exposure of S. cerevisiae to compound G2 resulted in a disappearance of the main sterol, ergosterol, from the cell membranes, suggesting that compound G2 was highly specific for ergosterol. Independently, chemical data indicated that compound G2 forms stable complexes with both ergosterol and cholesterol. Addition of cholesterol or ergosterol protected the cells of S. cerevisiae and several pathogenic yeasts from the inhibitory activity of compound G2 by producing a higher ratio of sterols (mainly ergosterol) to phospholipids in the membranes. The fact that an amphotericin B-resistant Candida tropicalis was susceptible to G2 suggested that its mode of action was different from that described for polyene antibiotics. This was also confirmed by the finding that 0.2 M KCl did not protect S. cerevisiae cells against ion leakage with G2, but did so with amphotericin B.

Original languageEnglish
Pages (from-to)504-512
Number of pages9
JournalZentralblatt fur Bakteriologie
Volume275
Issue number4
DOIs
StatePublished - 1991

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