How do the polyene macrolide antibiotics affect the cellular membrane properties

This review will survey environmental controls on the morphology of Candida albicans, describe the cellular and ultrastructural events associated with morphological transitions in this fungus, and attempt to relate biochemical phenomena that have been reported to be associated with dimorphic change to C albicans cell biology The synthesis of the cell wall of C albicans and its control remain largely undiscovered, but it is clear that the cell wall is the principal component involved in shape determination Possible models for C albicans dimorphism will be critically reviewed

Morphogenesis in Candida Albicans

The effect of ethanol on exponential phase cultures of S. cerevisiae has been examined using l-alanine uptake and proton efflux as indices of ethanol tolerance. Preincubation with 2 M ethanol inhibited l-alanine uptake, proton efflux and fermentation rates. However, the effect of ethanol varied in yeast cells enriched with different fatty acyl residues. It was observed that cells enriched with polyunsaturated fatty acids acquired greater tolerance to ethanol as compared to monounsaturated fatty acids. By varying the degree of unsaturation of supplemented fatty acid, a sequential insertion of double bonds in yeast membrane lipid was achieved. Results demonstrated that S. cerevisiae became more resistant to ethanol with an increase in the degree of unsaturation and that membrane fluidity could be an important determinant of ethanol tolerance.

Relationship between ethanol tolerance and fatty acyl composition of Saccharomyces cerevisiae

Publisher Summary This chapter discusses antimycotic drugs that are used in the therapy of human infections. It outlines the current knowledge of the mode of action of the clinically important antifungal drugs. The major targets for clinically important antimycotic drugs are the nucleus and cellular membranes. The two clinically important compounds—namely, griseofulvin and 5-fluorocytosine, act primarily at the level of the nucleus. Griseofulvin, a drug important in the chemotherapy of dermatophytic infections, interferes with nuclear organization. 5-Fluorocytosine, which is used in the chemotherapy of systemic candidosis and cryptococcosis, interferes with the synthesis of nucleic acids. 5-Fluorocytosine is itself non-toxic, but it is metabolized by sensitive cells to give a number of derivatives that exert a growth inhibitory effect, either as a result of their incorporation into cellular macromolecules or by an indirect inhibition of macromolecular synthesis. Much of the detailed understanding of the mode of action of this compound has been derived from studies on animal tissues and, where relevant, this information is used to supplement the experimental data derived from fungi.

Mode of action of clinically important antifungal drugs.

In this review, the cell envelope of the human pathogenic yeast Candida albicans includes the plasma membrane and the mannoproteins, enzymes, beta-glucans, and chitin of the wall. The organization of the wall is complex and ultrastructural studies show distinct "layers". Mannoprotein is distributed throughout the wall but is concentrated on the exterior surface and adjacent to the plasma membrane. The mannoproteins contain the antigenic determinants of the yeast cells. The major structural components of the wall are beta-1,3- and beta 1,6-glucans, and these two linkages are present in almost equal amounts. Chitin is concentrated at the bud scar, but small amounts are located over the entire wall where it appears to be linked to beta-1,6-glucan. Chemical bonding both within and between wall components confers rigidity on the wall and restricts movement of molecules into and out of the cell. Soluble enzymes are retained within the wall matrix, but a number of enzymes and proteins are excreted. The plasma membrane of C. albicans is similar to that isolated from other fungi and contains the proton pump ATPase and enzymes involved in biosynthesis of the wall such as chitin synthase and beta-1,3-glucan synthase.

Cell envelope of Candida albicans.

The effect of altered lipid composition on the transport of various amino acids in Candida albicans

The effect of altered ergosterol content on the transport of various amino acids in Candida albicans.

Characteristics of proline transport in normal and starved cells of Candida albicans.

An inducible proline transport system in Candida albicans

When Candida albicans cells were grown on hydroquinone (Hy cells) or ascorbic acid (As cells) supplemented media, they exhibited a 26% rise and 16% drop in ergosterol content, respectively. C. albicans cells manifested a gradual increase in total lipid levels, when they were grown on n-alkanes of different chain lengths. The magnitude of the nystatin effect (in terms of proline uptake and K+ efflux) was more pronounced in cells having more ergosterol (Hy cells) compared with the cells having low levels of ergosterol (As cells), suggesting a correlation between nystatin sensitivity and ergosterol content of the C. albicans cells. However, such correlation could not be demonstrated in alkane grown cells where levels of different lipids were variable. Results demonstrated that several other lipids besides sterol may also influence the polyene antibiotic sensitivity in C. albicans cells.

Manjeet Singh

Papers

The effect of altered lipid composition on the transport of various amino acids in Candida albicans

The effect of altered ergosterol content on the transport of various amino acids in Candida albicans.

Characteristics of proline transport in normal and starved cells of Candida albicans.

An inducible proline transport system in Candida albicans

Lipid composition and polyene antibiotic sensitivity in isolates of Candida albicans.