Cryptococcus neoformans: morphogenesis, infection, and evolution.

Cryptococcus neoformans is the major causative agent of fungal meningoencephalitis in both immunocompromised and immunocompetent individuals. During infection, this fungus is observed in the yeast form and is only occasionally seen as the pseudohyphal or hyphal form (filamentous forms). Early studies suggested that phase transition of C. neoformans from a multi-cellular filamentous form to the unicellular yeast form might be essential for the survival of this fungus in mammalian hosts. However, how different Cryptococcus morphotypes exhibit different levels of pathogenicity in hosts are unclear. This review discusses the possible roles of each form inside and outside of mammalian hosts and summarizes recent insights on the life cycle and morphogenesis of this fungus and their impact on the pathogenicity. Application of recently developed advanced tools for C. neoformans research may assist in understanding the genetic and molecular mechanisms of morphology-associated virulence in this important fungal pathogen. Research on the association between fungal dimorphism and pathogenicity has been traditionally limited to a few related ascomyceteous fungal pathogens. This review is to stimulate discussion and expansion of this type of investigation to a larger group of evolutionary divergent fungi capable of causing systemic fungal infections in humans. Hopefully, a common theme for the convergent evolution of virulence-associated morphology will emerge with future studies.