Dermatophytes cause the majority of superficial
mycoses in humans and animals. However, little is known about the pathogenicity of this specialized group of filamentous fungi, for which molecular research has been limited thus far. During experimental
infection of guinea pigs by the human pathogenic dermatophyte Arthroderma benhamiae, we recently detected the activation of the fungal gene encoding
malate synthase AcuE, a key
enzyme of the
glyoxylate cycle. By the establishment of the first genetic system for A. benhamiae, specific ΔacuE mutants were constructed in a wild-type strain and, in addition, in a derivative in which we inactivated the nonhomologous end-joining pathway by deletion of the A. benhamiae KU70 gene. The absence of AbenKU70 resulted in an increased frequency of the targeted insertion of linear
DNA by homologous recombination, without notably altering the monitored in vitro growth abilities of the fungus or its virulence in a guinea pig
infection model. Phenotypic analyses of ΔacuE mutants and complemented strains depicted that
malate synthase is required for the growth of A. benhamiae on
lipids, major constituents of the skin. However, mutant analysis did not reveal a pathogenic role of the A. benhamiae
enzyme in guinea pig
dermatophytosis or during epidermal invasion of the fungus in an in vitro model of reconstituted human epidermis. The presented efficient system for targeted genetic manipulation in A. benhamiae, paired with the analyzed
infection models, will advance the functional characterization of putative virulence determinants in medically important dermatophytes.