Differential gene expression in the pathogenic dermatophyte Arthroderma benhamiae in vitro versus during infection
2010
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.
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