Cited by 205Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Infections and Studies

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Genome-wide expression profiling of the response to polyene, pyrimidine, azole, and echinocandin antifungal agents in Saccharomyces cerevisiae.

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Agarwal, Ameeta K., Rogers, P.David, Baerson, Scott R., Jacob, Melissa R., Barker, Katherine S., Cleary, John D., Walker, Larry A., Nagle, Dale G., Clark, Alice M.·2003·Journal of Biological Chemistry

DOI 10.1074/jbc.m306291200

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Abstract

Antifungal compounds exert their activity through a variety of mechanisms, some of which are poorly understood. Novel approaches to characterize the mechanism of action of antifungal agents will be of great use in the antifungal drug development process. The aim of the present study was to investigate the changes in the gene expression profile of Saccharomyces cerevisiae following exposure to representatives of the four currently available classes of antifungal agents used in the management of systemic fungal infections. Microarray analysis indicated differential expression of 0.8, 4.1, 3.0, and 2.6% of the genes represented on the Affymetrix S98 yeast gene array in response to ketoconazole, amphotericin B, caspofungin, and 5-fluorocytosine (5-FC), respectively. Quantitative real time reverse transcriptase-PCR was used to confirm the microarray analyses. Genes responsive to ketoconazole, caspofungin, and 5-FC were indicative of the drug-specific effects. Ketoconazole exposure primarily affected genes involved in ergosterol biosynthesis and sterol uptake; caspofungin exposure affected genes involved in cell wall integrity; and 5-FC affected genes involved in DNA and protein synthesis, DNA damage repair, and cell cycle control. In contrast, amphotericin B elicited changes in gene expression reflecting cell stress, membrane reconstruction, transport, phosphate uptake, and cell wall integrity. Genes with the greatest specificity for a particular drug were grouped together as drug-specific genes, whereas genes with a lack of drug specificity were also identified. Taken together, these data shed new light on the mechanisms of action of these classes of antifungal agents and demonstrate the potential utility of gene expression profiling in antifungal drug development.

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Authors: Agarwal, A. K., Rogers, P. D., Baerson, S. R., Jacob, M. R., Barker, K. S., Cleary, J. D., Walker, L. A., Nagle, D. G., & Clark, A. M.
Affiliations: University of Mississippi (US)
University of Tennessee Health Science Center (US)
Agricultural Research Service (US)
University of Mississippi Medical Center (US)
Corresponding author: Agarwal, Ameeta K.
ORCID: Agarwal, Ameeta K.
Rogers, P.David
Baerson, Scott R.
Barker, Katherine S.
Cleary, John D.
Walker, Larry A.
Nagle, Dale G.
Clark, Alice M.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2003-09
Volume: 278
Issue: 37
Pages: 34998-35015
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m306291200
OpenAlex: W2106248803
Cited by: 204
References: 75
Citations by year: 2026: 2 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 8 · 2019: 6 · 2018: 3 · 2017: 11 · 2016: 3 · 2015: 6 · 2014: 4 · 2013: 10 · 2012: 10
FWCI: 11.73
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 6236 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: U.S. Department of Agriculture (58‐6408‐2‐0009)
National Institutes of Health
U.S. Public Health Service
Agricultural Research Service (58-6408-2- 0009)
National Institute of Allergy and Infectious Diseases (R01AI027094, R01-AI 27094, AI 27094)
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Health Sciences › Medicine › Infectious Diseases › Fungal Infections and Studies
Keywords: antifungal agents, Saccharomyces cerevisiae, gene expression profiling, ketoconazole, amphotericin B, caspofungin, 5-fluorocytosine, polyene antibiotics, azole antifungals, echinocandins, ergosterol biosynthesis, cell wall integrity, DNA repair, cell cycle regulation, mechanism of action, antifungal drug development
MeSH terms: Anti-Bacterial Agents, Antifungal Agents, Azoles, Base Sequence, Ketoconazole, Peptides, Polyenes, Pyrimidines, Saccharomyces cerevisiae, Structure-Activity Relationship, Gene Expression Regulation, Fungal, Genome, Fungal, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling

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Genome-wide expression profiling of the response to polyene, pyrimidine, azole, and echinocandin antifungal agents in Saccharomyces cerevisiae.

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