Abstract
Successive reculturing of Saccharomyces cerevisiae on media containing increasing concentrations of nystalin led to the segregation of cell populations which are resistant to 30, 100, 200, and 300 U/ml of antibiotic. Since the crucial step in the antifungal action of nystatin is considered to be its binding with the membrane sterol, the sterol content of each resistant isolate was ascertained. Nys-30 isolates (resisstant to 30 U/ml of nystatin) were found to contain principally 5,6-dihydroergosterol, the immediate biogenetic precursor of ergosterol in the sensitive parent culture. The principle sterols of isolates resistant to successively higher concentrations of nystatin represented successively more primitive ergosterol precursors. These observations were interpreted to mean that resistance to nystatin in S. cerevisiae is not developed in a random fashion. Indeed, at the molecular level, the development of resistance involves an orderly selection for naturally occurring strains devoid of the ability to perform some of the enzymatic transformations required for the production of ergosterol.
Published Version
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