Lipid composition and polyene antibiotic resistance of Candida albicans mutants

Four polyene-resistant mutants (C7, E4, C4, D10) of Candida albicans were derived by mutagenesis with N-methyl-N′-nitro-N-nitrosoguanidine followed by isolation on nystatin-containing medium. The mutants were cross resistant to amphotericin B, lucensomycin, and candicidin and showed the same order of increasing resistance to the four polyenes tested, i.e., C7 < E4 < C4 < D10. Free sterols, sterol esters, and phospholipid fatty acids were analyzed in the mutants and sensitive parent strain. The lipids of C7 were the same as those of the sensitive parent strain. Mutant E4 contained lichesterol and other Δ8-sterols indicating a block at the Δ8→ Δ7 isomerase, and most of the sterol ester fraction consisted of 4,14-desmethyl sterols. The most resistant mutants C4 and D10 had reduced growth rates, alterations in phospholipid fatty acids, and the absence of 4,14-desmethyl sterols. Mutants C4 and D10 had similar lipid compositions with 24-methylenelanosterol as the major sterol and lesser amounts of obtusifoliol ...