Isolation of mutants of Candida glabrata resistant to miconazole.

Elucidation of the mode of action of azole antifungals would be aided by studying resistant mutants. It is difficult to obtain mutants of Candida albicans in the laboratory, and there have only been a few studies on clinical isolates which seem to be resistant because of impaired drug uptake. C. glabrata, unlike C. albicans, is haploid and more likely to give rise to resistant variants. Over 30 mutants have been isolated by selection with miconazole on solid medium and have MICs of miconazole about ten times that of the parental strain. One such mutant has a reduced growth rate and final cell yield. In intact cells, ergosterol biosynthesis is tenfold less sensitive to miconazole than in the parent. However, uptake of [3H]miconazole by cells is identical in both strains. The significance of these observations is discussed.