Haloprogin: mode of action studies in Candida albicans

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Abstract
The relative antifungal properties of haloprogin, a new synthetic antimicrobial agent, and two polyene antibiotics, amphotericin B and nystatin, were determined in Candida albicans. The specific parameters studied included possible effects on (i) cell viability, (ii) oxygen utilization, (iii) uptake and incorporation of labelled leucine and uridine, and (iv) loss of intracellular K+ ions. Susceptibility of mammalian erythrocytes to lysis by these antimicrobial agents was also determined. Fungicidal activity of haloprogin appears to be attributable to inhibition of oxygen uptake and disruption of the cell membrane. Haloprogin affects protein and nucleic acid synthesis to a lesser degree as evidenced by uptake and incorporation of labelled precursors. The two polyene antibiotics act in a different manner; nystatin effectively inhibits oxygen utilization and incorporation of leucine and uridine, whereas amphotericin B affects primarily leucine incorporation. Both polyene drugs disturb the cell membrane as shown by intracellular loss of potassium ions from C. albicans cells and lysis of mammalian erythrocytes.

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