Subinhibitory concentration of octenidine and pirtenidine: influence on the lipid and sterol contents of Candida albicans.

The effect of subinhibitory concentrations of octenidine and pirtenidine on the lipid and sterol composition of Candida albicans was investigated. The total lipid and sterol contents of C. albicans grown in the presence of either octenidine or pirtenidine were reduced compared with control-grown cells. The major differences in the lipid composition of drug-grown and control cells were phosphatidylglycerol, phosphatidylcholine and monogalactosyldiacylglycerol, which increased in the presence of octenidine and pirtenidine. Lower proportions of phosphatidic acid were found in yeasts grown in the presence of the drugs when compared with control C. albicans. Fatty acid analysis of control-grown cells showed that the major fatty acids were C16 and C18. Drug-grown cells had higher proportions of palmitic and linolenic acids but lower proportion of oleic acid. The C16/C18 ratios were higher for octenidine- and pirtenidine-grown cells than control cells. Differences in the fatty acid composition of major phospholipids and neutral lipids between drug-grown and control yeasts were also observed. Sterol analysis of control-grown cells showed that the major sterol present was ergosterol (65.9%). A significant increase in squalene and 4,14-dimethylzymosterol was observed in pirtenidine-treated cells, while octenidine-treated cells showed an increase in zymosterol and obtusifoliol contents. Our results suggest that octenidine and pirtenidine affect the lipids and sterol of C. albicans in different ways. The implications of these findings on the mode of action of these two drugs is discussed.

Variation in lipid and sterol contents in Candida albicans white and opaque phenotypes.

In the white-opaque transition, cells of Candida albicans strain WO-1 switch reversibly and at high frequency between phases which differ both in colony and cellular phenotype. The lipid and sterol contents of the two phases were compared. White cells were higher in lipid and sterol contents in both mid-exponential and stationary phase cultures. In mid-exponential phase cultures, the lipids of white cells accumulated substantial amounts of apolar compounds, including steryl esters, alkyl esters, triacylglycerols, fatty acids, free sterols and mono- and di-glycerides, while opaque cells accumulated nearly equal proportions of apolar and and polar compounds, mainly phosphatidylethanolamines and phosphatidylcholines. In stationary phase cultures, both white and opaque cells had slightly higher proportions of polar lipids. Major differences in the lipid composition between white and opaque cells involved the contents of free sterols and derivatives of sterols. White cells contained higher proportions of free sterols than opaque cells, while opaque cells contained more steryl glycosides and steryl esters (approximately 2.5 times higher). Comparison of the sterols of the white and opaque cells by UV, TLC and GLC showed that a qualitative as well as quantitative difference exists between the two phenotypes. Fatty acid analysis of white and opaque cells showed that C-16 and C-18 fatty acids are the most abundant in both phenotypes. White and opaque cells varied in their fatty acid composition. The former had higher proportions of palmitoleic (16:1) and stearic (18:0) but lower proportions of linoleic (18:2) fatty acids than opaque cells. Analysis of fatty acids of major lipid classes present in both forms showed that fatty acid pattern varied dramatically according to whether the class had been isolated from white or opaque cells. Our results suggest that the lipid composition (particularly sterol and polyunsaturated fatty acids) of the opaque phenotype resembles that of mycelial cultures. Opaque cells showed more resistance to amphotericin B, nystatin, 5-fluorocytosine (flucytosine) and miconazole nitrate than white cells.