Evaluation of differential gene expression in fluconazole-susceptible and -resistant isolates of Candida albicans by cDNA microarray analysis

Phillip Rogers, Katherine S. Barker

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73 Citations (Scopus)

Abstract

The opportunistic fungal pathogen Candida albicans is the major causative agent of oropharyngeal candidiasis (OPC) in AIDS. The development of azoles, such as fluconazole, for the treatment of OPC has proven effective except in cases where C. albicans develops resistance to fluconazole during the course of treatment. In the present study, we used microarray technology to examine differences in gene expression from a fluconazole-susceptible and a fluconazole-resistant well-characterized, clinically obtained matched set of C. albicans isolates to identify genes which are differentially expressed in association with azole resistance. Among genes found to be differentially expressed were those involved in amino acid and carbohydrate metabolism; cell stress, cell wall maintenance; lipid, fatty acid, and sterol metabolism; and small molecule transport. In addition to CDR1, which has previously been demonstrated to be associated with azole resistance, the drug resistance gene RTA3, the ergosterol biosynthesis gene ERG2, and the cell stress genes CRD2, GPX1, and IFD5 were found to be upregulated. Several genes, such as the mitochondrial aldehyde dehydrogenase gene ALD5, the glycosylphosphatidylinositol synthesis gene GP11, and the iron transport genes FET34 and FTR2 were found to be downregulated. Further study of these differentially regulated genes is warranted to evaluate how they may be involved in azole resistance. In addition to these novel findings, we demonstrate the utility of microarray analysis for studying the molecular mechanisms of drug resistance in pathogenic organisms.

Original languageEnglish (US)
Pages (from-to)3412-3417
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume46
Issue number11
DOIs
StatePublished - Nov 1 2002

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Fluconazole
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Candida albicans
Gene Expression
Azoles
Genes
Candidiasis
Drug Resistance
Ergosterol
Glycosylphosphatidylinositols
Carbohydrate Metabolism
Sterols
Cell Wall
Acquired Immunodeficiency Syndrome
Fatty Acids
Down-Regulation
Iron
Maintenance
Technology

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

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