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Antimicrobial Agents and Chemotherapy, June 2001, p. 1660-1670, Vol. 45, No. 6
Department of Advanced Bio-Technologies,
Janssen Research Foundation, B-2340 Beerse,1 and
Steenweg op Gierle 68, B-2300 Turnhout,3
Belgium, and Department of Bio-informatics, R. W. Johnson Pharmaceutical Research Institute, San Diego, California
921212
Received 22 January 2001/Returned for modification 15 February
2001/Accepted 2 March 2001
The application of genome-wide expression profiling to determine
how drugs achieve their therapeutic effect has provided the pharmaceutical industry with an exciting new tool for drug
mode-of-action studies. We used DNA chip technology to study cellular
responses to perturbations of ergosterol biosynthesis caused by the
broad-spectrum antifungal agent itraconazole. Simultaneous examination
of over 6,600 Candida albicans gene transcript levels,
representing the entire genome, upon treatment of cells with 10 µM
itraconazole revealed that 296 genes were responsive. For 116 genes
transcript levels were decreased at least 2.5-fold, while for 180 transcript levels were similarly increased. A global upregulation of
ERG genes in response to azole treatment was observed.
ERG11 and ERG5 were found to be upregulated
approximately 12-fold. In addition, a significant upregulation was
observed for ERG6, ERG1, ERG3, ERG4, ERG10, ERG9, ERG26, ERG25,
ERG2, IDII, HMGS, NCP1, and FEN2, all of which are
genes known to be involved in ergosterol biosynthesis. The effects of
itraconazole on a wide variety of known metabolic processes are
discussed. As over 140 proteins with unknown function were responsive
to itraconazole, our analysis might provide
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.6.1660-1670.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Genomic Profiling of the Response of Candida
albicans to Itraconazole Treatment Using a DNA
Microarray

in combination with
phenotypic data
first hints of their potential function. The present
report is the first to describe the application of DNA chip technology
to study the response of a major human fungal pathogen to drug treatment.
*
Corresponding author. Present address: Department of
Immunology (2517D), R. W. Johnson Pharmaceutical Research
Institute, 3210 Merryfield Row, San Diego, CA 92121. Phone: (858)
784-3110. Fax: (858) 450-2081. E-mail:
mdebacke{at}prius.jnj.com.
Present address: Arcturus, San Diego, CA 92121.
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