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In Candida albicans ATCC 10261, two kinetically different amino acid transport systems with a high (S~) and a low ($2) affinity for aspartic acid (asp) and glutamic acid (glu) were identified. The $1 for the two acidic amino acids was characterized by low Kt values while Kt values of Sz were 30 to 40 times higher. Based on competitive studies of both systems, $1 was found to be specific and common to both asp and glu while $2 was relatively less specific. The Sl and $2 systems were also different in their sensitivity to respiratory inhibitors, mercurials and a K ÷ channel blocker. Both systems, however, showed maximum transport rates during the mid-exponential growth phase.

The primary mode of action of azoles is the inhibition of cytochrome P‐450 dependent 14α‐demethylase, a key enzyme in ergosterol biosynthesis in fungi. Our results demonstrated that Candida albicans cells grown in the presence of 10 μg ml−1 of miconazole (miconazole‐grown), do not possess ergosterol in their plasma membranes and this ergosterol depletion leads to a drastic change in membrane fluidity as shown by fluorescence polarization measurements and unsaturation index. There was an increase in membrane order in miconazole‐grown cells and a reduced rate of uptake of amino acids. We also checked for membrane permeability changes in normal mid‐log phase cells (normal‐grown) in short incubations (10 min) with 10 μg ml−1 miconazole (miconazole‐incubated). Interestingly, the amino acid uptake rates except that Gly were not affected significantly in these cells. The results suggest that in the miconazole‐incubated cells, the drug is not able to alter the level of ergosterol of inhibit ergosterol biosynthesis during 10 min incubation and therefore the interaction of the drug neither leads to significant disorganization of membrane components, nor affects permease activity, whereas in the miconazole‐grown cells there is ergosterol depletion leading to accumulation of biosynthetic intermediates, resulting in membrane rearrangement thereby causing a major fluidity change. This fluidity change may explain the drastic reduction of amino acid transport in miconazole‐grown cells. To investigate whether the reduction in amino acid transport was only due to change in membrane fluidity, as a consequence of absence of ergosterol, the PM‐ATPase activity was checked in the miconazole‐grown cells and was found to be unaffected, which suggests that changes in amino acid uptake were due to change in membrane fluidity.

Phosphate uptake studies in different strains of the dimorphic pathogenic yeast Candida albicans were undertaken to show that this yeast actively transported phosphate with an apparent Km in the range of 90–170 μM. The uptake was pH dependent and derepressible under phosphate starvation. Vanadate‐resistant (van) mutants of C. albicans showed a 20–70% reduction in the rate of phosphate uptake in high phosphate medium and was associated with an increased Km and reduced Vmax. The magnitude of depression under phosphate starvation was different between van mutants. These results demonstrate that van mutants may have developed resistance by modifying the rate of entry of vanadate.

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