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Mechanisms of Action: Physiological Effects

Genome-Wide Expression Profiling of the Response to Azole, Polyene, Echinocandin, and Pyrimidine Antifungal Agents in Candida albicans

Teresa T. Liu, Robin E. B. Lee, Katherine S. Barker, Richard E. Lee, Lai Wei, Ramin Homayouni, P. David Rogers
Teresa T. Liu
1Departments of Pharmacy
2Children's Foundation Research Center at Le Bonheur Children's Medical Center, Memphis, Tennessee 38103
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Robin E. B. Lee
3Pharmaceutical Sciences
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Katherine S. Barker
1Departments of Pharmacy
2Children's Foundation Research Center at Le Bonheur Children's Medical Center, Memphis, Tennessee 38103
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Richard E. Lee
3Pharmaceutical Sciences
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Lai Wei
4Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163
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Ramin Homayouni
4Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163
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P. David Rogers
1Departments of Pharmacy
2Children's Foundation Research Center at Le Bonheur Children's Medical Center, Memphis, Tennessee 38103
3Pharmaceutical Sciences
5College of Pharmacy, and Departments of Pediatrics
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  • For correspondence: drogers@utmem.edu
DOI: 10.1128/AAC.49.6.2226-2236.2005
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ABSTRACT

Antifungal agents exert their activity through a variety of mechanisms, some of which are poorly understood. We examined changes in the gene expression profile of Candida albicans following exposure to representatives of the four currently available classes of antifungal agents used in the treatment of systemic fungal infections. Ketoconazole exposure increased expression of genes involved in lipid, fatty acid, and sterol metabolism, including NCP1, MCR1, CYB5, ERG2, ERG3, ERG10, ERG25, ERG251, and that encoding the azole target, ERG11. Ketoconazole also increased expression of several genes associated with azole resistance, including CDR1, CDR2, IFD4, DDR48, and RTA3. Amphotericin B produced changes in the expression of genes involved in small-molecule transport (ENA21), and in cell stress (YHB1, CTA1, AOX1, and SOD2). Also observed was decreased expression of genes involved in ergosterol biosynthesis, including ERG3 and ERG11. Caspofungin produced changes in expression of genes encoding cell wall maintenance proteins, including the β-1,3-glucan synthase subunit GSL22, as well as PHR1, ECM21, ECM33, and FEN12. Flucytosine increased the expression of proteins involved in purine and pyrimidine biosynthesis, including YNK1, FUR1, and that encoding its target, CDC21. Real-time reverse transcription-PCR was used to confirm microarray results. Genes responding similarly to two or more drugs were also identified. These data shed new light on the effects of these classes of antifungal agents on C. albicans.

  • Copyright © 2005 American Society for Microbiology
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Genome-Wide Expression Profiling of the Response to Azole, Polyene, Echinocandin, and Pyrimidine Antifungal Agents in Candida albicans
Teresa T. Liu, Robin E. B. Lee, Katherine S. Barker, Richard E. Lee, Lai Wei, Ramin Homayouni, P. David Rogers
Antimicrobial Agents and Chemotherapy May 2005, 49 (6) 2226-2236; DOI: 10.1128/AAC.49.6.2226-2236.2005

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Genome-Wide Expression Profiling of the Response to Azole, Polyene, Echinocandin, and Pyrimidine Antifungal Agents in Candida albicans
Teresa T. Liu, Robin E. B. Lee, Katherine S. Barker, Richard E. Lee, Lai Wei, Ramin Homayouni, P. David Rogers
Antimicrobial Agents and Chemotherapy May 2005, 49 (6) 2226-2236; DOI: 10.1128/AAC.49.6.2226-2236.2005
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KEYWORDS

antifungal agents
Candida albicans
Fungal Proteins
Gene Expression Profiling
Genome, Fungal
Oligonucleotide Array Sequence Analysis

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