Genome-Wide Expression Profile Analysis Reveals Coordinately Regulated Genes Associated with Stepwise Acquisition of Azole Resistance in Candida albicans Clinical Isolates
Open Access
- 1 April 2003
- journal article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 47 (4), 1220-1227
- https://doi.org/10.1128/aac.47.4.1220-1227.2003
Abstract
Candida albicans is an opportunistic human fungal pathogen and a causative agent of oropharyngeal candidiasis (OPC), the most frequent opportunistic infection among patients with AIDS. Fluconazole and other azole antifungal agents have proven effective in the management of OPC; however, with increased use of these agents treatment failures have occurred. Such failures have been associated with the emergence of azole-resistant strains of C. albicans . In the present study we examined changes in the genome-wide gene expression profile of a series of C. albicans clinical isolates representing the stepwise acquisition of azole resistance. In addition to genes previously associated with azole resistance, we identified many genes whose differential expression was for the first time associated with this phenotype. Furthermore, the expression of these genes was correlated with that of the known resistance genes CDR1 , CDR2 , and CaMDR1 . Genes coordinately regulated with the up-regulation of CDR1 and CDR2 included the up-regulation of GPX1 and RTA3 and the down-regulation of EBP1 . Genes coordinately regulated with the up-regulation of CaMDR1 included the up-regulation of IFD1 , IFD4 , IFD5 , IFD7 , GRP2 , DPP1 , CRD2 , and INO1 and the down-regulation of FET34 , OPI3 , and IPF1222 . Several of these appeared to be coordinately regulated with both the CDR genes and CaMDR1 . Many of these genes are involved in the oxidative stress response, suggesting that reduced susceptibility to oxidative damage may contribute to azole resistance. Further evaluation of the role these genes and their respective gene products play in azole antifungal resistance is warranted.Keywords
This publication has 52 references indexed in Scilit:
- Bioassay of cadmium using a DNA microarray: Genome-wide expression patterns ofSaccharomyces cerevisiaeresponse to cadmiumEnvironmental Toxicology and Chemistry, 2001
- Phosphorylation of the Yeast Phospholipid Synthesis Regulatory Protein Opi1p by Protein Kinase CPublished by Elsevier BV ,2001
- Turnover of Phosphatidylcholine in Saccharomyces cerevisiaePublished by Elsevier BV ,2001
- Phospholipid and sterol analysis of plasma membranes of azole-resistantCandida albicansstrainsFEMS Microbiology Letters, 2000
- A genomic locus in Saccharomyces cerevisiae with four genes up‐regulated by osmotic stressMolecular Microbiology, 1995
- Resistance of Candida albicans to Fluconazole During Treatment of Oropharyngeal Candidiasis in a Patient with AIDS: Documentation by In Vitro Susceptibility Testing and DNA Subtype AnalysisClinical Infectious Diseases, 1994
- The prevalence of oral lesions in HIV-infected homosexual and bisexual menAIDS, 1991
- Role of the glutathione-glutathione peroxidase cycle in the cytotoxicity of the anticancer quinonesPharmacology & Therapeutics, 1990
- The Lipid Composition of Azole-sensitive and Azole-resistant Strains of Candida albicansMicrobiology, 1986
- Oral Candidiasis in High-Risk Patients as the Initial Manifestation of the Acquired Immunodeficiency SyndromeThe New England Journal of Medicine, 1984