Clues About Chromoblastomycotic and Other Dematiaceous Fungal Pathogens Based on Wangiella as a Model

Abstract

Wangiella dermatitidis is an excellent model for discovering biologically and medically relevant information about other dematiaceous agents of mycosis. The major attribute of this phaeohyphomycotic fungus, which allows it to serve as a useful model, is its vegetative polymorphism. This polymorphism is expressed both in vivo and in vitro and programs a number of developmental choices leading to polarized growth by budding and hyphal apical extension or to a type of non-polarized, isotropic growth that produces spherically enlarged cells and multicellular forms. The latter phenotypes are virtually identical to the sclerotic bodies of chromoblastomycotic fungi. Study of the phenotypic switching between the polarized and isotropic growth forms has been possible because Wangiella can be induced to form the multicellular bodies from yeasts or hyphae in vitro by manipulation of culture medium pH, or by the incubation of certain cell-divisioncycle mutants at elevated temperatures. It is evident that this particular type of dimorphism involves considerable rearrangement of cell-wall synthetic and deposition patterns, and results from the inhibition of polarized budding or hyphal apical extension, without the inhibition of isotropic growth, nuclear division or cytokinesis. It is also becoming evident that Ca²⁺ may have a major regulatory role in the switching, because new results showed that at acidic pH a low, but critical, concentration of Ca²⁺ was crucial for multicellular-body development, higher concentrations allowed maintenance of polarized growth, and that a Ca²⁺/proton exchange mechanism might be involved. Support for this important role for Ca²⁺ has also been provided by other new results with EGTA. At high concentrations and at near neutral pH, this Ca²⁺ chelator caused a stage-specific, cell-cycle arrest in yeast cells, but at lower concentrations induced increasing numbers of cells to convert to multicellular forms. Parallel studies with the chromoblastomycotic fungi showed that Ca²⁺ also maintained the polarized growth of hyphae at very acidic pH, and that withholding Ca²⁺ by low concentrations of EGTA at more neutral pH induced isotropism and the formation of sclerotic bodies. These preliminary results with Ca²⁺ and the chromoblastomycotic fungi further validate the concept that W. dermatitidis continues to be an important model for dematiaceous pathogens of humans.