Basis of cerulenin resistance of two strains of Candida albicans.
The basis of cerulenin resistance of Candida albicans strains 4918-2 and 4918-10 has been investigated. Parasexual genetic analyses established that cerulenin resistance to concentrations of at least 5 micrograms ml-1 is dominant in both strains. The results also showed that strain 4918-2 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 uptake 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 was restored in UV-induced cerulenin-sensitive segregants of strains 4918-2 and 4918-10, and varied from 63% to 200% of parental values. Fatty-acid synthase from strains 4918-2 and 4918-10 was resistant to cerulenin as judged by differences in the inactivation of the enzyme by the agent. However, inactivation kinetics of fatty-acid synthase of cerulenin-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 micrograms ml-1 while strain 4918 was sensitive to cerulenin at all concentrations tested. Thus, the results suggest that alteration of fatty-acid synthase and changes in permeability contribute to total cerulenin resistance of each strain.
McElhaney-Feser
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Department of Microbiology and Immunology, Georgetown University, Washington, DC 20007, USA.
Cihlar
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RL
D002176:Candida albicans / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects; D002463:Cell Membrane Permeability; D002569:Cerulenin / Q000378:metabolism* / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006579:Heterozygote; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D011995:Recombination, Genetic; D013997:Time Factors; D014466:Ultraviolet Rays
D002569:Cerulenin; D064429:Fatty Acid Synthases