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Is Cryptococcus neoformans a pleomorphic fungus?

Summary

Cryptococcus neoformans is a dangerous fungal pathogen that causes serious infections in humans. For many years, scientists thought this fungus existed primarily as regular yeast cells. However, new research shows the fungus can change into several different cell forms during infection, including larger ‘titan cells’ and smaller ‘seed cells.’ These shape-shifting abilities help the fungus survive in the human body and evade immune responses, making infections harder to treat.

Background

Cryptococcus neoformans has been classically described as a basidiomycete budding yeast with a distinctive polysaccharide capsule. Recent research has revealed multiple infection-relevant single cell morphologies in vivo and in vitro that were previously unrecognized, suggesting a more complex cellular biology than historically appreciated.

Objective

To determine whether newly discovered morphologies of C. neoformans constitute true morphotypes and whether C. neoformans should be reclassified as a pleomorphic fungus. The authors establish criteria for defining morphotypes and examine recent discoveries of seed cells and titan cells within this framework.

Results

Multiple C. neoformans single-cell morphologies including yeast, seed cells, and titan cells are transcriptionally distinct, stable, heritable, and associated with active growth. Additional potential morphotypes identified include titanides, microcells, and viable but nonculturable cells. These diverse morphologies show distinct environmental triggers and phenotypic characteristics relevant to pathogenesis.

Conclusion

C. neoformans should be classified as a pleomorphic fungus with important capacity for morphotype switching that underpins pathogenesis. The fungus exhibits at least three true morphotypes (yeast, seed cells, and titan cells) with several additional candidates, and morphotype switching is critical for environmental stress resistance and dissemination during infection.
  • Published in:Current Opinion in Microbiology,
  • Study Type:Review,
  • Source: PMID: 39260180, DOI: 10.1016/j.mib.2024.102539
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