Journal of Antimicrobial Chemotherapy (2000) 46, 191-197
© 2000 The British Society for Antimicrobial Chemotherapy
Modulation of fluconazole sensitivity by the interaction of mitochondria and Erg3p in Saccharomyces cerevisiae
The University of Texas M. D. Anderson Cancer Center, Section of Infectious Diseases, 1515 Holcombe Boulevard, Box 47, Houston, TX 77030, USA
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 ¢5,6 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.
* Corresponding author. Tel: +1-713-792-0826; Fax: +1-713-794-4351; E-mail: dkontoyi{at}notes.mdacc.tmc.edu
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Yan, M. Li, Y. Cao, P. Gao, Y. Cao, Y. Wang, and Y. Jiang The alternative oxidase of Candida albicans causes reduced fluconazole susceptibility J. Antimicrob. Chemother., October 1, 2009; 64(4): 764 - 773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Vandeputte, G. Tronchin, F. Rocher, G. Renier, T. Berges, D. Chabasse, and J.-P. Bouchara Hypersusceptibility to Azole Antifungals in a Clinical Isolate of Candida glabrata with Reduced Aerobic Growth Antimicrob. Agents Chemother., July 1, 2009; 53(7): 3034 - 3041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. G. Oliver, P. M. Silver, C. Marie, S. J. Hoot, S. E. Leyde, and T. C. White Tetracycline alters drug susceptibility in Candida albicans and other pathogenic fungi Microbiology, March 1, 2008; 154(3): 960 - 970. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Vandeputte, G. Larcher, T. Berges, G. Renier, D. Chabasse, and J.-P. Bouchara Mechanisms of Azole Resistance in a Clinical Isolate of Candida tropicalis Antimicrob. Agents Chemother., November 1, 2005; 49(11): 4608 - 4615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kaur, I. Castano, and B. P. Cormack Functional Genomic Analysis of Fluconazole Susceptibility in the Pathogenic Yeast Candida glabrata: Roles of Calcium Signaling and Mitochondria Antimicrob. Agents Chemother., May 1, 2004; 48(5): 1600 - 1613. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Brun, T. Berges, P. Poupard, C. Vauzelle-Moreau, G. Renier, D. Chabasse, and J.-P. Bouchara Mechanisms of Azole Resistance in Petite Mutants of Candida glabrata Antimicrob. Agents Chemother., May 1, 2004; 48(5): 1788 - 1796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-Y. S. Moosa, J. D. Sobel, H. Elhalis, W. Du, and R. A. Akins Fungicidal Activity of Fluconazole against Candida albicans in a Synthetic Vagina-Simulative Medium Antimicrob. Agents Chemother., January 1, 2004; 48(1): 161 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Y. Young, C. M. Hull, and J. Heitman Disruption of Ergosterol Biosynthesis Confers Resistance to Amphotericin B in Candida lusitaniae Antimicrob. Agents Chemother., September 1, 2003; 47(9): 2717 - 2724. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Brun, C. Aubry, O. Lima, R. Filmon, T. Berges, D. Chabasse, and J.-P. Bouchara Relationships between Respiration and Susceptibility to Azole Antifungals in Candida glabrata Antimicrob. Agents Chemother., March 1, 2003; 47(3): 847 - 853. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mukhopadhyay, A. Kohli, and R. Prasad Drug Susceptibilities of Yeast Cells Are Affected by Membrane Lipid Composition Antimicrob. Agents Chemother., December 1, 2002; 46(12): 3695 - 3705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. Kontoyiannis and G. S. May {{delta}}-Aminolaevulinic acid modulates the resistance to fluconazole in a hem1 mutant of Saccharomyces cerevisiae J. Antimicrob. Chemother., December 1, 2000; 46(6): 1044 - 1046. [Full Text] [PDF]
|
|