Studies on the Mode of Action of Antifungal Heptaene Antibiotics

Publisher Website
Google Scholar
Abstract
The effect of heptamycin (an antif ungal heptaene antibiotic closely related to the ascosin-candicidin-trichomycin group) on the respiration of Candida albicans was studied. Heptamycin inhibited the oxidation of pyruvate, lactate and trehalose to a considerable degree. The oxidation of glucose, acetate, acetaldehyde and ethanol was only slightly affected by heptamycin. Anaerobic glycolysis was significantly inhibited. No inhibition of cell-free preparations of trehalase (obtained from C. albicans) or pyruvic carboxylase (from C. albicans and Saccharomyces carlsbergensis) was observed; CO2 output by cell-free preparations was not affected either. The uptake of pyruvate and trehalose by C. albicans cells is apparently due to an active and inducible mechanism; heptamycin inhibits oxidation of these substances by blocking their penetration into the yeast cell. The oxidation of trehalose in induced organisms was not inhibited by heptamycin whereas that of pyruvate was. Heptamycin, candicidin B, ascosin, trichomycin and amphotericin B inhibited phosphate uptake by non-proliferating suspensions of C. albicans. The inhibition was observed at fungistatic concentrations (0.5-5 [mu]g./ml.) and without any preincubation with the antibiotic. Phosphate uptake by Debaryomyces nicotianae, Pichia farinosa, Cryptococcus albidus and Saccharomyces cerevisiae was similarly affected by heptamycin. Esterification of inorganic phosphate by cell-free extracts of C. albicans was not affected by heptamycin. It is suggested that the fungistatic effect of heptaene antibiotics upon sensitive yeasts is mainly due to the prevention of phosphate uptake.