cDNA microarray analysis of differential gene expression and regulation in clinically drug-resistant isolates of Candida albicans from bone marrow transplanted patients

Fungi have emerged as the fourth most common pathogens isolated in nosocomial bloodstream infections, andCandida albicans is the most common human fungal pathogen. Only a few antibiotics are effective in the treatment offungal infections. In addition, the repetition and lengthy duration of fluconazole therapy has led to an increasedincidence of azole resistance and treatment failure associated with C. albicans. To investigate the mechanism of drugresistance and explore new targets to treat clinically resistant fungal pathogens, we examined the large-scale geneexpression profile of two sets of matched fluconazole-susceptible and -resistant bloodstream C. albicans isolates frombone marrow transplanted (BMT) patients for the first time by microarray analysis. More than 198 differentiallyexpressed genes were identified and they were confirmed and validated by RT-PCR independently. Not surprisingly,the resistant phenotype is associated with increased expression of CDR mRNA, as well as some common genesinvolved in drug resistance such as CaIFU5, CaRTA2 and CaIFD6. Meanwhile, some special functional groups ofgenes, including ATP binding cassette (ABC) transporter genes (IPF7530, CaYOR1, CaPXA1), oxidative stressresponse genes (CaALD5, CaGRP1, CaSOD2, IPF10565), copper transport and iron mobilization-related genes(CaCRD1/2, CaCTR1/2, CaCCC2, CaFET3) were found to be differentially expressed in the resistant isolates.Furthermore, among these differentially expressed genes, some co-regulated with CaCDR1, CaCDR2 and CaIFU5,such as CaPDR16 and CaIFD6, have a DRE-like element and may interact with TAC1 in the promoter region. Thesefindings may shed light on mechanisms of azole resistance in C. albicans and clinical antifungal therapy.