Molecular genetic studies of the model dematiaceous pathogen Wangiella dermatitidis.

The rapidly improving molecular genetic tractability of Wangiella (Exophiala) dermatitidis significantly enhances its usefulness as a model for the more than 100 other dematiaceous (melanized) agents of human disease. Previously this model was based almost exclusively on its vegetative polymorphism, which at the simplest level is expressed as three well-characterized modes of growth (e.g., blastic, apical and isotropic) that produce myriad yeast, hyphal and sclerotic phenotypes. This cellular plasticity is important for a dematiaceous model pathogen because some are hyphal in nature but exist almost exclusively as sclerotic bodies in infected tissue, whereas others are hyphal both in nature and in tissue, and still others exist in nature predominantly as yeast, but as mixtures of yeast, hyphae and sclerotic bodies in tissue. By exploiting the polymorphism of W. dermatitidis, any phenotype of another dematiaceous pathogen can be produced for study of the regulation of its development and its contribution to pathogenicity and virulence. The coupling of this asset with the recent finding that its haploid, uninucleate yeast cell is easily transformed molecularly, and the even more recent development of systems for both random and targeted gene disruptions and for site-specific, integrative gene overexpression studies suggest that it will continue as the preferred model for the dematiaceous fungi and irrespective of the mycosis involved. The results reviewed here aim to confirm this contention, stimulate others to study this fungus, and demonstrate that W. dermatitidis is exceptionally useful for discovering by molecular genetic techniques cell wall-associated virulence factors in fungi, and in particular in the dematiaceous fungi.