Studies on the mechanism of synergistic action with synergisidin and imidazole antimycotics.

Abstract

The investigation of mechanism of synergistic action with SYN and ECZ was performed using C. albicans SC5314 so that SYN was confirmed to show strong synergistic effects against Candida sp. in particular with addition of extremely small quantities under the MICs of imidazole antimycotics such as ECZ, MCZ and CTZ. The synergistic effect of antifungal activity against C. albicans SC5314 with a combination of SYN and ECZ (SYN + ECZ) showed fungistatic action. Effect of SYN + ECZ on osmotic resistance was not recognized and protoplast was not observed under a microscope. Accordingly, SYN + ECZ was considered not to take part in cell wall synthesis directly. For effect of SYN + ECZ on release of intracellular components, slow release of 260 nm-absorbing substances was occurred, so that SYN + ECZ was seemed not to affect cytoplasmic membrane damage directly. Also, it was suggested clearly that SYN + ECZ affected lipid metabolism and glycolysis including TCA cycle from the investigation on antagonism by growth recovery of C. albicans SC5314 by 106 kinds of substances such as fatty acids, isoprenoids, phospholipids, vitamins, amino acids, nucleic acid-related substances and TCA cycle-related substances. From the above results, it was suggested that the mechanism of synergistic action with SYN and ECZ against C. albicans SC5314 was due to affect the different reactions in lipid metabolism and the similar reactions in glycolysis including TCA cycle, respectively, in consideration of respective mechanism of actions of SYN alone and ECZ alone. A part of this work was presented at the Annual Meeting of the Agricultural Chemical Society of Japan, 1981 (Kyoto).