The lipid composition and permeability to azole of an azole- and polyene-resistant mutant of Candida albicans

Abstract

Candida albicans 6.4, which is resistant to both polyene and azole groups of antifungal antibiotics, has a larger lipid content and lower polar lipid to neutral lipid ratio compared with other strains that are sensitive or resistant only to azoles. C. albicans 6.4 contains a relatively greater proportion of triacylglycerol in its neutral lipid in the exponential phase of batch culture compared with other strains, but, unlike them, does not accumulate triacylglycerols or any other stored lipid in the stationary phase. Like other strains, in C. albicans 6.4 the major phospholipids are phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol, but sphingomyelin is absent; the major fatty acids are palmitic, palmitoleic, oleic and linoleic acids. In common with other C. albicans strains, strain 6.4 contains non-specific (lyso)phospholipase activity. The main distinctive feature of the lipid composition of C. albicans 6.4 is the absence of ergosterol, which is replaced by methylated sterol; mainly lanosterol, 24-methylene-24,25-dihydrolanosterol and 4-methylergostadiene-3-ol. It is suggested that the altered membrane sterol pattern provides a common basis for the double resistance by preventing polyene binding and reducing azole permeability.