Phospholipase A and lysophospholipase activities were measured in the culture fluid and in the blastospores of Candida albicans. When phospholipase activity was measured in six yeasts (four strains of C. albicans and a single strain each of Candida parapsilosis and Saccharomyces cereuisiae) a correlation was found between this activity and two potential parameters of pathogenicity. The C. albicans isolates which adhered most strongly to buccal epithelial cells and were most pathogenic in mice had the highest phospholipase activities. Non-pathogenic yeasts, including C. albicans isolates which did not adhere and did not kill mice, had lower p hosp holi pase activities.

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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...

(6S)-6-Fluoroshikimic acid inhibited the growth of Escherichia coli B on minimal medium (MIC, 0.25 micrograms ml-1), and it protected mice challenged intraperitoneally with the same organism (50% protective dose, 0.06 mg kg of body weight-1). We propose that inhibitors of bacterial aromatic biosynthesis have the potential for use in human medicine.

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.Polyenes and azoles (N-substituted imidazoles and triazoles) are clinically the most important antifungal antibiotics for the treatment of candidosis [ 14,19]. The modes of action of polyenes and azoles are related in that both types disrupt membrane properties such as permeability by interfering with lipid components, especially sterols. Polyenes bind directly to sterols causing the leakage of essential ions and low molecular weight metabolites [8,9]. Azoles appear to have several effects on membrane lipid synthesis, but their primary action is probably inhibition of synthesis of ergosterol leading to accumulation of methylated sterol precursors which disrupt membrane functions; at higher concentrations azoles may also interact directly with membrane lipids [for reviews see refs 5 and 21 ].There are differences between the actions of different azoles, and several aspects remain unclear. One approach to resolving this uncertainty is by the use of mutants.Clinical isolates of C. albicans resistant to polyenes are rare, but a number of mutants