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Updated: Jun 18, 2026
Gene Expression Profiling of Infecting Microbes Using a Digital Bar-coding Platform
Published on: January 13, 2016
Differential gene expression in the pathogenic dermatophyte Arthroderma benhamiae in vitro versus during infection
Peter Staib1, Christophe Zaugg2, Bernard Mignon3
1Leibniz Institute for Natural Product Research and Infection Biology - Hans Knoell Institute, Junior Research Group Fundamental Molecular Biology of Pathogenic Fungi, Beutenbergstr. 11a, D-07745 Jena, Germany.
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. In vitro 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 Arthroderma benhamiae, which causes highly inflammatory cutaneous infections in humans and rodents. By use of a cDNA microarray covering approximately 20-25 % of the A. benhamiae genome and containing sequences of at least 23 protease genes, we revealed a distinct in vivo protease gene expression profile in the fungal cells, which was surprisingly different from the pattern elicited during in vitro growth on keratin. Instead of the major in vitro -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 Trichophyton rubrum 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 A. benhamiae, 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.
Insights
This study reveals that dermatophyte fungi use different proteases during infection than previously thought. Key virulence factors, including subtilisin 6, are upregulated during host invasion, offering new insights into fungal pathogenicity.
Area of Science:
- Medical Mycology
- Molecular Pathogenesis
- Fungal Genetics
Background:
- Dermatophytes cause common superficial mycoses, but their pathogenicity mechanisms remain poorly understood.
- Secreted proteases are hypothesized to enable keratin degradation and host colonization.
- Previous research focused on in vitro protease activity, potentially missing in vivo-specific functions.
Purpose of the Study:
- To investigate the in vivo gene expression profile of secreted proteases in the dermatophyte Arthroderma benhamiae during infection.
- To identify novel virulence factors and pathogenicity mechanisms of dermatophytes in a host environment.
- To compare in vivo protease gene expression with in vitro keratin degradation patterns.
Main Methods:
- Established a guinea pig infection model for Arthroderma benhamiae.
- Utilized a cDNA microarray to analyze gene expression of approximately 20-25% of the A. benhamiae genome, including 23 protease genes.
- Compared gene expression profiles during in vitro growth on keratin versus in vivo infection.
Main Results:
- Discovered a distinct in vivo protease gene expression profile, differing significantly from in vitro keratin degradation patterns.
- Identified specific proteases upregulated during infection, suggesting roles beyond simple keratinolysis.
- Found that the serine protease subtilisin 6 gene was the most highly upregulated during infection, a known allergen.
- Identified other potential virulence factors, including glyoxylate cycle enzymes and an opsin-related protein.
Conclusions:
- Dermatophytes employ unique sets of proteases during host infection, with functions extending beyond keratin degradation.
- Subtilisin 6 and other identified factors represent key virulence mechanisms in dermatophyte pathogenicity.
- This study provides the first broad-scale gene expression profile of pathogenic dermatophytes during infection, illuminating their success in causing superficial mycoses.
