Candida albicans is the most common fungal pathogen, causing skin and mucosal infections in generally healthy individuals, life-threatening infections in immunocompromised patients, and leading to death in up to 50% of patients with bloodstream infections.
1,2)C. albicans is known for its unstable genome. The instability of the chromosome copy number of entire chromosomes, as well as the large portions of chromosomes was extensively studied with laboratory and freshly isolated strains using pulse-field gene electrophoresis (PFGE) as reviewed by Rustchenko,3) Rustchenko and Sherman,4) and Selmecki et al. 5) Combined with Southern blot analysis, PFGE allowed limited analysis of gene copy number, and also could be extended to the analysis of chromosome deletions and other rearrangements. [6][7][8][9][10][11][12][13][14][15] Recently, array technology opened a new dimension in the study of genome instability. Array comparative genomic hybridization (array CGH) allows the detection of genomic variations across a whole genome. When the CGH intensity data are plotted as a function of position on the genetic map, aneuploidy of chromosomes or chromosomal segments are readily identified. The availability of the C. albicans strain SC5314 genome sequence has allowed the construction of microarrays for the analysis of gene copy number. Berman's laboratory largely used array CGH to demonstrate aneuploidies in C. albicans derivatives of the sequencing strain SC5314, several laboratory strains, as well as clinical isolates, as reviewed by Selmecki et al.
5)Also, Thewes et al. 16) used array CGH to elucidate the genomic diversity among C. albicans less virulent strain ATCC10231 and the reference sequencing strain SC5314 in the hope to uncover genetic basis of pathogenicity. Although some variable genes were identified, this study was limited to a single strain.Despite the extensive effort of various laboratories, a comprehensive study, which would include various strains and which would focus on the DNA sequence and gene copy number variability is still lacking, although this approach was applied to other organisms, including Saccharomyces cerevisiae. 17,18) In order to fill this need, we examined the genomic contents of eight clinical isolates, as compared to the SC5314 reference strain, using array CGH. The Cluster Along Chromosomes (CLAC) algorithm was employed to identify variable genes. Medical School; Rochester, N.Y., 14642, U.S.A.: and c Department of Pharmacology, School of Pharmacy, Second Military Medical University; Shanghai 200433, China. Received October 25, 2010; accepted January 24, 2011; published online February 16, 2011 Genome plasticity is a hallmark of Candida albicans and is believed to be an adaptation strategy. But the extent of such genomic variability is not well investigated. In this study, genetic contents of clinical C. albicans isolates were investigated at whole-genome level with array-based comparative genomic hybridization (array CGH) technology. It was revealed that C. albicans possess...