Basis of cerulenin resistance of two strains of Candida albicans

• Published in: Microbiology (Society for General Microbiology) Vol. 141; no. 7; pp. 1553 - 1558
• Main Authors: McElhaney-Feser, Gail, Cihlar, Ronald L
• Format: Journal Article
• Language: English
• Published: Reading Soc General Microbiol 01.07.1995; Society for General Microbiology
• Subjects: Biological and medical sciences; Candida albicans; Candida albicans - drug effects; Candida albicans - genetics; Candida albicans - metabolism; Candida albicans - radiation effects; Cell Membrane Permeability; Cerulenin - metabolism; Cerulenin - pharmacology; Drug Resistance, Microbial; Fatty Acid Synthases - antagonists & inhibitors; Fatty Acid Synthases - genetics; Fatty Acid Synthases - metabolism; Fundamental and applied biological sciences. Psychology; Growth, nutrition, metabolism, transports, enzymes. Molecular biology; Heterozygote; Kinetics; Microbial Sensitivity Tests; Microbiology; Mycology; Recombination, Genetic; Time Factors; Ultraviolet Rays; Candida albicans; Acyltransferases; Yeast; Enzyme; Transferases; Uptake; Fatty-acid synthase; Mechanism; Fungi; Antibiotic; Antifungal agent; Sensitivity resistance; Membrane transport; Fungi Imperfecti; Thallophyta
• ISSN: 1350-0872; 1465-2080
• DOI: 10.1099/13500872-141-7-1553

Department of Microbiology and Immunology, Georgetown University, Washington, DC 20007, USA ABSTRACT Summary: 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 µg 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 µg 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. 1 Author for correspondence: Ronald Cihlar. Tel: +1 202 687 1136. Fax: +1 202 687 1800. Keywords: Candida albicans , cerulenin, resistance, fatty-acid synthase, uptake