This study examined nystatin-resistant mutants of Candida albicans and C. krusei isolated from patients with candidiasis. The resistant strains completely lacked ergosterol, the fungal membrane sterol that serves as the binding site for nystatin. When these resistant strains were cultured on medium supplemented with ergosterol (10 μg/ml), they gradually became sensitive to nystatin within 5 days, achieving sensitivities identical to wild-type cells. Sterol analysis confirmed that supplemented resistant strains accumulated ergosterol to levels similar to sensitive controls. Importantly, this sensitivity was reversible: when resistant strains were returned to ergosterol-free medium, they recovered nystatin resistance within 5 days. The authors propose that sterol incorporation into fungal membranes requires active growth and occurs at specific membrane sites, distinguishing Candida from organisms lacking natural sterols. This work demonstrates that nystatin resistance in Candida is ergosterol-dependent and can be modulated through environmental sterol availability.

Key findings

• Nystatin-resistant Candida strains lacked ergosterol entirely, while sensitive strains contained 1-7% ergosterol by dry weight
• Culturing resistant strains on ergosterol-supplemented medium for 5 days restored nystatin sensitivity to wild-type levels
• Resistance was reversible, returning when ergosterol-supplemented strains were recultured on unsupplemented medium
• Sterol incorporation into Candida membranes requires active growth, distinguishing it from rapid sterol uptake in organisms lacking natural sterols