MORAN G., STOKES C., THEWES S., HUBE B., COLEMAN C. AND SULLIVAN D., COMPARATIVE GENOMICS USING CANDIDA ALBICANS DNA MICROARRAYS REVEALS ABSENCE AND DIVERGENCE OF VIRULENCE ASSOCIATED GENES IN CANDIDA DUBLINIENSIS, MICROBIOLOGY, 150, 10, 2004, 3363 - 3382
MICROBIOLOGY 150 10
Candida dubliniensis is a pathogenic yeast species closely related to Candida albicans. However, it is less
frequently associated with human disease and displays reduced virulence in animal models of infection. We
have used comparative genomic hybridisaion (CGH) in order to discover why C. dubliniensis is apparently
less virulent than C. albicans. In these experiments we compared the genomes of the two species by cohybridising
C. albicans microarrays with fluorescently labeled C. albicans and C. dubliniensis genomic
DNA. We found that C. dubliniensis genomic DNA hybridised reproducibly to 96% percent of C. albicans
gene-specific sequences indicating a significant degree of nucleotide sequence homology (> 60%) in these
sequences. The remaining 4% of sequences (representing 234 genes) gave C. albicans/C. dubliniensis
normalised fluorescent signal ratios indicative of significant sequence divergence (< 60% homology) or
absence in C. dubliniensis. We identified sequence divergence in several genes (confirmed by Southern Blot
analysis and sequencing analysis of PCR products) with putative virulence functions including the gene
encoding the hypha-specific human transglutaminase substrate Hwp1p. Poor hybridisation of C. dubliniensis
genomic DNA to the secreted aspartyl proteinase encoding gene SAP5 array sequences also led us to
determine that SAP5 was absent in C. dubliniensis and that this species possesses only one gene homologous
to SAP4 and SAP6 of C. albicans. In addition, divergence and absence of sequences in several gene families
was identified including a family of HYR1-like GPI-anchored proteins, a family of genes homologous to a
putative transcriptional activator (CTA2) and several ALS genes. This study has confirmed the close
relatedness of C. albicans and C. dubliniensis and has identified a subset of unique C. albicans genes that
may contribute to the increased prevalence and virulence of this species.
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