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Clinical strains ofCandida albicansare highly tolerant of aneuploidies and other genome rearrangements. We have used comparative genome hybridization (CGH), in an array format, to analyse the copy number of over 6000 open reading frames (ORFs) in the genomic DNA ofC. albicanslaboratory strains carrying one (CAI-4) to three (BWP17) auxotrophies. We find that during disruption of theHIS1locus all genes telomeric toHIS1were deleted and telomeric repeats were added to a 9 nt sequence within the transforming DNA. This deletion occurred in∼10% of transformants analysed and was stably maintained through two additional rounds of transformation and counterselection of the transformation marker. In one example, the deletion was repaired, apparently via break-induced replication. Furthermore, all CAI-4 strains tested were trisomic for chromosome 2 although this trisomy appears to be unstable, as it is not detected in strains subsequently derived from CAI-4. Our data indicate CGH arrays can be used to detect monosomies and trisomies, to predict the sites of chromosome breaks, and to identify chromosomal aberrations that have not been detected with other approaches inC. albicansstrains. Furthermore, they highlight the high level of genome instability inC. albicanslaboratory strains exposed to the stress of transformation and counterselection on 5-fluoro-orotic acid. [ABSTRACT FROM AUTHOR]

The human pathogenCandida albicansgrows and colonizes sites that can vary markedly in pH. The pH response inC. albicansis governed in part by the Rim101p pathway. InSaccharomyces cerevisiae, Rim101p promotes alkaline responses by repressing expression ofNRG1, itself a transcriptional repressor. Our studies reveal that inC. albicans, Rim101p-mediated alkaline adaptation is not through repression ofCaNRG1. Furthermore, our studies suggest that Rim101p and Nrg1p act in parallel pathways to regulate hyphal morphogenesis, an important contributor to virulence. To determine the wild-typeC. albicanstranscriptional response to acidic and alkaline pH, we utilized microarrays and identified 514 pH-responsive genes. Of these, several genes involved in iron acquisition were upregulated at pH 8, suggesting that alkaline pH induces iron starvation. Microarray analysis ofrim101–/– cells indicated that Rim101p does not govern transcriptional responses at acidic pH, but does regulate a subset of transcriptional responses at alkaline pH, including the iron acquisition genes. We found thatrim101–/– cells are sensitive to iron starvation, which suggests that one important aspect of the Rim101p-dependent alkaline pH response is to adapt to iron starvation conditions. [ABSTRACT FROM AUTHOR]