Reference: Kontoyiannis DP (2000) Modulation of fluconazole sensitivity by the interaction of mitochondria and erg3p in Saccharomyces cerevisiae. J Antimicrob Chemother 46(2):191-7

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Abstract


We studied the effects of fluconazole, an ergosterol-depleting agent, in Saccharomyces cerevisiae, a genetically tractable fungus closely related to Candida albicans. The wild-type Saccharomyces strain was sensitive to fluconazole, but the isogenic cytoplasmic petite mutant (rho-) was resistant. The mechanism of resistance of rho- mutants appeared to involve uncoupling of oxidative phosphorylation. However, the petite strain with a mutation in cent5, 6 desaturase (erg3 rho-) was sensitive to fluconazole, in contrast to its erg3 rho+ counterpart. It is known that erg3 mutants are azole resistant through the accumulation of 14-methyl-fecosterol, a less toxic ergosterol intermediate. These results indicate that mitochondria function as important physiological partners with Erg3p in the accumulation of toxic sterol intermediates in the presence of azoles.

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Journal Article | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, P.H.S.
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Kontoyiannis DP
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