Comparative gene expression analysis by differential clustering approach: application to the Candida albicans transcription program.
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ABSTRACT:
SUBMITTER: Ihmels J
PROVIDER: S-EPMC1239936 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Candida dubliniensis is closely related to Candida albicans; however, it is responsible for fewer infections in humans and is less virulent in animal models of infection. C. dubliniensis forms fewer hyphae in vivo, and this may contribute to its reduced virulence. In this study we show that, unlike C. albicans, C. dubliniensis fails to form hyphae in yeast extract-peptone-dextrose (YPD) medium supplemented with 10% (vol/vol) fetal calf serum (YPDS medium). However, C. dubliniensis filaments in water plus 10% (vol/vol) fetal calf serum (WS), and this filamentation is inhibited by the addition of peptone and glucose. Repression of filamentation in YPDS medium could be partly overcome by preculture in synthetic Lee's medium. Unlike C. albicans, inoculation of C. dubliniensis in YPDS medium did not result in increased UME6 transcription. However, >100-fold induction of UME6 was observed when C. dubliniensis was inoculated in nutrient-poor WS medium. The addition of increasing concentrations of peptone to WS medium had a dose-dependent effect on reducing UME6 expression. Transcript profiling of C. dubliniensis hyphae in WS medium identified a starvation response involving expression of genes in the glyoxylate cycle and fatty acid oxidation. In addition, a core, shared transcriptional response with C. albicans could be identified, including expression of virulence-associated genes including SAP456, SAP7, HWP1, and SOD5. Preculture in nutrient-limiting medium enhanced adherence of C. dubliniensis, epithelial invasion, and survival following coculture with murine macrophages. In conclusion, C. albicans, unlike C. dubliniensis, appears to form hyphae in liquid medium regardless of nutrient availability, which may account for its increased capacity to cause disease in humans.
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Project description:Candida dubliniensis is the closest known relative of Candida albicans, the most pathogenic yeast species in humans. However, despite both species sharing many phenotypic characteristics, including the ability to form true hyphae, C. dubliniensis is a significantly less virulent and less versatile pathogen. Therefore, to identify C. albicans-specific genes that may be responsible for an increased capacity to cause disease, we have sequenced the C. dubliniensis genome and compared it with the known C. albicans genome sequence. Although the two genome sequences are highly similar and synteny is conserved throughout, 168 species-specific genes are identified, including some encoding known hyphal-specific virulence factors, such as the aspartyl proteinases Sap4 and Sap5 and the proposed invasin Als3. Among the 115 pseudogenes confirmed in C. dubliniensis are orthologs of several filamentous growth regulator (FGR) genes that also have suspected roles in pathogenesis. However, the principal differences in genomic repertoire concern expansion of the TLO gene family of putative transcription factors and the IFA family of putative transmembrane proteins in C. albicans, which represent novel candidate virulence-associated factors. The results suggest that the recent evolutionary histories of C. albicans and C. dubliniensis are quite different. While gene families instrumental in pathogenesis have been elaborated in C. albicans, C. dubliniensis has lost genomic capacity and key pathogenic functions. This could explain why C. albicans is a more potent pathogen in humans than C. dubliniensis.
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