Project description:Azole resistance was induced in vitro by growth of a susceptible C. parapsilosis isolate in the presence of fluconazole. Whole genome microarrays were used to compare the transcriptional response of the fluconazole-resistant and susceptible isolates.
Project description:Transcriptional profiling of Candida albicans comparing fluconazole treated cells with fluconazole- and berberine-treated cells, as well untreated cells with berberine treated cells
Project description:This SuperSeries is composed of the following subset Series: GSE27405: Transcriptional response of an azole-resistant Candida parapsilosis isolate [fluconazole]. GSE27407: Transcriptional response of an azole-resistant Candida parapsilosis isolate [posaconazole]. GSE27408: Transcriptional response of an azole-resistant Candida parapsilosis isolate [voriconazole]. Refer to individual Series
Project description:Azole resistance was induced in vitro by growth of a susceptible C. parapsilosis isolate in the presence of fluconazole. Whole genome microarrays were used to compare the transcriptional response of the fluconazole-resistant and susceptible isolates. Transcriptional profile of in vitro derived fluconazole resistant isolate of C. parapsilosis (BC014FLC) compared to susceptible isolate (BC014S). Cell were grown in YPD medium in normoxia at 35 degrees. Each strain was labelled with Cy3 or Cy5. Overall, 4 independent biological replicates were compared; 2 dye swaps were performed to normalize dye effects.
Project description:Purpose: We compared the expression profile of three fluconazole resistant clinical isolates to two fluconazole sensitive clinical isolates, from the same patient, all containing mutation in the trancription factor Mrr1, to define the Mrr1 regulon in Candida lusitaniae.
Project description:In the pathogenic yeast Candida albicans, the zinc cluster transcription factor Upc2p has been shown to regulate expression of ERG11 and other genes involved in ergosterol biosynthesis upon exposure to azole antifungals. ERG11 encodes lanosterol demethylase, the target enzyme of this antifungal class. Over-expression of UPC2 reduces azole susceptibility, whereas its disruption results in hypersusceptibility to azoles and reduced accumulation of exogenous sterols. Constitutive up-regulation of ERG11 is a major cause of resistance to fluconazole in clinical isolates of C. albicans, yet the mechanism for this has yet to be determined. Using genome-wide gene expression profiling, we found UPC2 and other genes involved in ergosterol biosynthesis to be coordinately up-regulated with ERG11 in a fluconazole resistant clinical isolate as compared with a matched susceptible isolate from the same patient. Sequence analysis of the UPC2 alleles of these isolates revealed that the resistant isolate contained a single nucleotide substitution in one UPC2 allele that resulted in a G648D exchange in the encoded protein. Introduction of the mutated allele into a drug susceptible strain resulted in constitutive up-regulation of ERG11 and increased resistance to fluconazole. By comparing the gene expression profiles of the fluconazole resistant isolate and of strains carrying wild-type and mutated UPC2 alleles, we identified target genes that are controlled by Upc2p. Here we show for the first time that a gain-of-function mutation in UPC2 leads to increased expression of ERG11 and imparts resistance to fluconazole in clinical isolates of C. albicans. Keywords: genome-wide expression profiling
