Is Cryptococcus neoformans a pleomorphic fungus?

Improved understanding of the human fungal pathogen Cryptococcus neoformans, classically described as a basidiomycete budding yeast, has revealed new infection-relevant single cell morphologies in vivo and in vitro. Here, we ask whether these morphologies constitute true morphotypes, requiring updated classification of C. neoformans as a pleomorphic fungus. We profile recent discoveries of C. neoformans seed cells and titan cells and provide a framework for determining whether these and other recently described single-cell morphologies constitute true morphotypes. We demonstrate that multiple C. neoformans single-cell morphologies are transcriptionally distinct, stable, heritable, and associated with active growth and therefore should be considered true morphotypes in line with the classification in other well-studied fungi. We conclude that C. neoformans is a pleomorphic fungus with an important capacity for morphotype switching that underpins pathogenesis.