Reversal by calcium ions of the growth inhibition of Debaryomyces nicotianae caused by antifungal polyene antibiotics.

Only Debaryomyces nicotianae strain 77, of seven different yeast strains tested, was found to be resistant to heptamycin and other antifungal heptaenes when grown in a rich medium. This strain, however, like the other six, was completely susceptible to these antibiotics in a minimal medium. Addition of yeast extract to the minimal medium abolished the heptamycin effect; calcium ions fully duplicated the effect of yeast extract; Mg(2+) and Mn(2+) were also effective but less so than Ca(2+). Ca(2+) also counteracted the activity of the heptaenes ascosin and trichomycin. Complete reversal of the polyene inhibition by Ca(2+) was obtained if the cation was added simultaneously with the antibiotic; addition of Ca(2+) 2 hr after the polyene was without effect. Addition of Ca(2+) in the absence of the polyene caused a slight, if any, growth stimulation of D. nicotianae 77. Cholesterol also counteracted polyene activity; this was due to the formation of a complex with the antibiotic which prevented the polyene from reaching the site of action-the cytoplasmic membrane. No evidence for complex formation between heptamycin and calcium was found. The importance of Ca(2+) in membrane structure, as evidenced from heptaene studies, is discussed.