1887

Abstract

Although dermatophytes are the most common agents of superficial mycoses in humans and animals, the molecular basis of the pathogenicity of these fungi is largely unknown. digestion of keratin by dermatophytes is associated with the secretion of multiple proteases, which are assumed to be responsible for their particular specialization to colonize and degrade keratinized host structures during infection. To investigate the role of individual secreted proteases in dermatophytosis, a guinea pig infection model was established for the zoophilic dermatophyte , which causes highly inflammatory cutaneous infections in humans and rodents. By use of a cDNA microarray covering approximately 20–25 % of the genome and containing sequences of at least 23 protease genes, we revealed a distinct protease gene expression profile in the fungal cells, which was surprisingly different from the pattern elicited during growth on keratin. Instead of the major -expressed proteases, others were activated specifically during infection. These enzymes are therefore suggested to fulfil important functions that are not exclusively associated with the degradation of keratin. Most notably, the gene encoding the serine protease subtilisin 6, which is a known major allergen in the related dermatophyte and putatively linked to host inflammation, was found to be the most strongly upregulated gene during infection. In addition, our approach identified other candidate pathogenicity-related factors in , such as genes encoding key enzymes of the glyoxylate cycle and an opsin-related protein. Our work provides what we believe to be the first broad-scale gene expression profile in human pathogenic dermatophytes during infection, and points to putative virulence-associated mechanisms that make these micro-organisms the most successful aetiological agents of superficial mycoses.

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2010-03-01
2019-10-21
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Scatter plot comparing gene expression levels in during guinea pig infection (gp) versus growth on Sabouraud control medium [PDF](225 KB)

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Identification of genes that were differentially expressed in during growth in soy medium, keratin–soy medium and during infection as compared with Sabouraud, respectively [Excel file](343 KB)

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Identification of genes that were commonly upregulated during growth of in soy and keratin–soy medium, and specifically upregulated in keratin–soy medium, respectively [Excel file](82 KB)

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Identification of genes that are specifically regulated in during infection as compared with keratin–soy [Excel file](278 KB)

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