BASIS OF CERULENIN RESISTANCE OF 2 STRAINS OF CANDIDA-ALBICANS

The basis of cerulenin resistance of Candida albicans strains 4918-2 a nd 4918-10 has been investigated. Parasexual genetic analyses establis hed that cerulenin resistance to concentrations of at least 5 mu g ml( -1) is dominant in both strains. The results also showed that strain 4 918-2 is heterozygous for resistance, while the change from resistance to sensitivity of strain 4918-10 is reversible. Experiments to define the mechanism(s) responsible for resistance focused on cerulenin upta ke and fatty-acid synthase activity. Cerulenin uptake by strains 4918- 2 and 4918-10 was 24% of that of the wild-type (strain 4918). Uptake w as restored in UV-induced cerulenin-sensitive segregants of strains 49 18-2 and 4918-10, and varied from 63% to 200% of parental values. Fatt y-acid synthase from strains 4918-2 and 4918-10 was resistant to cerul enin as judged by differences in the inactivation of the enzyme by the agent. However, inactivation kinetics of fatty-acid synthase of cerul enin-sensitive segregants did not revert to the parental inactivation profile. Further investigation showed that nine out of ten segregants were resistant to cerulenin at concentrations between 1 and 4 mu g ml( -1) while strain 4918 was sensitive to cerulenin at all concentrations tested. Thus, the results suggest that alteration of fatty-acid synth ase and changes in permeability contribute to total cerulenin resistan ce of each strain.