The Lipid Composition of Azole-sensitive and Azole-resistant Strains of Candida albicans

Abstract

The lipid compositions of two azole-sensitive (A and B2630) and two azole-resistant (AD and KB) strains of the opportunistic fungal pathogen Candida albicans were studied by using several lipid extraction procedures: no differences were observed between the lipid content or total phospholipid/neutral lipid ratios of the four strains. All contained phosphatidylethanolamine, phosp hatidylc holine, phosphatid ylinosi to1 and p hosp hat id ylserine as major phospholipids, with smaller amounts of phosphatidylglycerol and diphosphatidylglycerol ; the relative proportions of these lipids differed between all four strains. The fatty acid composition of each major phospholipid within each strain differed, and there were also interstrain differences. A marked effect of culture growth phase in batch culture on lipid composition was observed. The major neutral lipids in each strain were triacylglycerol, non-esterified sterol and non-esterified fatty acid. The fatty acid compositions of the three fatty-acid-containing neutral lipids were distinct from each other and the phospholipids, and there were also interstrain differences. All strains possessed (1yso)phospholipase activity, which was nonspecific. The proportions of triacylglycerol and non-esterified fatty acid did not vary between strains, but the azole-resistant strains AD and KB contained more non-esterified sterol, giving them a phospholipid/sterol ratio approximately half that of azole-sensitive strains. There appeared to be a relationship between the phospholipid/sterol ratio of exponentially growing sensitive strains and their ability to take up azole; this did not extend to the resistant strains, which either did not take up azole (AD and KB) or took it up at a faster rate (Darlington) than sensitive strains. INTRODUCTIONCandida albicans is a widespread and troublesome opportunistic pathogen that causes a variety of superficial and deep-seated mycoses (Odds, 1979). Of the relatively few antifungal antibiotics available, those most commonly used to treat candidosis are the polyenes and the more recently introduced imidazoles (Speller, 1980). Polyenes work by complexing with membrane sterols (Hamilton-Miller, 1973). The primary action of imidazoles is probably inhibition of ergosterol synthesis that leads to an accumulation of 14a-methyl sterols which disrupt membrane structure and function (Van den Bossche et ul., 1982, 1983). However, imidazole actions are complex: they also inhibit a number of other yeast (and mammalian) membrane-bound enzymes (Uno et al., Mason et al., 1985), and at higher concentrations some of them affect yeast membranes by direct interaction with lipids (Cope, 1980; Brasseur et al., 1983).Clinical isolates of C. albicans vary considerably in their sensitivities to imidazoles (e.g. see Ryley et al., 1984), and azole-resistant strains have been isolated (Holt & Azmi, 1978 ;Horsburgh & Kirkpatrick, 1983; Warnock et al., 1983). The failure of two of these resistant strains (AD and , 1984). This might be due to an altered membrane lipid compos...

Drug Susceptibilities of Yeast Cells Are Affected by Membrane Lipid Composition

“…It has been shown that some of the azole-resistant C. albicans isolates exhibit altered membrane phospholipid and sterol compositions (15,23,30). Such lipid changes are observed both in clinical and in in vitro-adapted azole-resistant isolates of C. albicans (16,17,23,30). We as well as others have observed that Cdr1p and Pdr5p are sensitive to fluctuations in the lipid environment, where functions mediated by these drug extrusion pumps are selectively affected (19,47).…”

Lipidomics of Candida albicans biofilms reveals phase-dependent production of phospholipid molecular classes and role for lipid rafts in biofilm formation

“…Since altered lipid composition (e.g. alteration in sterol levels) is known to be a mechanism of resistance in planktonic Candida cells (Hitchcock et al, 1986;Mago & Khuller, 1989) as well as in Candida biofilms (Mukherjee et al, 2003), it is possible that the increase in unsaturated index in Candida biofilms (of early phase) may contribute to alterations in membrane fluidity, biofilm maturation and resistance against antifungal agents. Our studies also revealed that the PC : PE ratio increased during biofilm maturation, along with a decrease in acyl unsaturation, which may indicate a reduction in the propensity of the membrane to undergo a transition to hexagonal phase (non-bilayer), a feature that may relate to the attachment of the biofilms.…”

Chitinase Activity from Candida albicans and its Inhibition by Allosamidin

“…C. albicans (serotype A; NCPF 3153) was maintained on Sabouraud's dextrose agar (Oxoid) and grown in Sabouraud's dextrose broth (Oxoid) essentially as described by Hitchcock et al (1986). Under these conditions the organisms grew exclusively in the yeast phase.…”