Phase-specific gene expression underlying morphological adaptations of the dimorphic human pathogenic fungus, Coccidioides posadasii

• Coccidioides posadasii is a dimorphic fungal pathogen that grows as a Wlamentous saprobe in the soil and as endosporulating spheruleswithin the host. To identify genes speciWc to the pathogenic phase of Co. posadasii, we carried out a large-scale study of gene expression intwo isolates of the species. From the sequenced Co. posadasii genome, we chose 1000 open reading frames to construct a 70-mer microarray.RNA was recovered from both isolates at three life-cycle phases: hyphae, presegmented spherules, and spherules releasing endospores.Comparative hybridizations were conducted in a circuit design, permitting comparison between both isolates at all three life-cyclephases, and among all life-cycle phases for each isolate. By using this approach, we identiWed 92 genes that were diVerentially expressedbetween pathogenic and saprobic phases in both fungal isolates, and 43 genes with consistent diVerential expression between the two parasiticdevelopmental phases. Genes with elevated expression in the pathogenic phases of both isolates included a number of genes thatwere involved in the response to environmental stress as well as in the metabolism of lipids. The latter observation is in agreement withprevious studies demonstrating that spherules contain a higher proportion of lipids than saprobic phase tissue. Intriguingly, we discoveredstatistically signiWcant and divergent levels of gene expression between the two isolates proWled for 64 genes. The results suggest thatincorporating more than one isolate in the experimental design oVers a means of categorizing the large collection of candidate genes thattranscriptional proWling typically identiWes into those that are strain-speciWc and those that characterize the entire species.

Ämnesord

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Nyckelord

Development

Spherules

Endospores

Microarray

Fungal pathogen

Population

Cell and molecular biology

Cell- och molekylärbiologi

Publikations- och innehållstyp

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