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Antimicrobial Agents and Chemotherapy, June 2001, p. 1660-1670, Vol. 45, No. 6
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

Marianne D. De Backer,1,* Tatiana Ilyina,1 Xiao-Jun Ma,2,dagger Sandy Vandoninck,1 Walter H. M. L. Luyten,1 and Hugo Vanden Bossche3

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---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.

dagger Present address: Arcturus, San Diego, CA 92121.

Antimicrobial Agents and Chemotherapy, June 2001, p. 1660-1670, Vol. 45, No. 6
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.6.1660-1670.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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