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Is Cryptococcus neoformans a pleomorphic fungus?

Summary

Researchers have discovered that Cryptococcus neoformans, a dangerous fungus that causes serious infections, is actually much more shape-shifting than previously thought. Instead of existing as just one simple budding yeast form, the fungus can transform into several different cell types including large ‘titan cells’ and small ‘seed cells,’ each with different characteristics that help it survive and spread in the body. These different forms have distinct genetic programs and can evade the immune system in different ways, making the infection harder to treat. This discovery fundamentally changes how scientists understand this pathogen and could lead to new treatment strategies.

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 underappreciated, suggesting the organism may be more morphologically complex than traditionally understood.

Objective

To evaluate whether recently discovered morphologies of C. neoformans including seed cells and titan cells constitute true morphotypes and to establish a framework for determining if C. neoformans should be reclassified as a pleomorphic fungus rather than a simple budding yeast.

Results

Multiple C. neoformans single-cell morphologies including yeast, seed cells, and titan cells were found to be transcriptionally distinct, stable, heritable, and associated with active growth. Additional candidate morphotypes including titanides and microcells were identified as potentially representing true morphotypes with distinct biological properties relevant to pathogenesis.

Conclusion

C. neoformans should be classified as a pleomorphic fungus with an important capacity for morphotype switching that underpins pathogenesis. The discovery of multiple morphotypes with distinct cell wall and secreted factor profiles has important implications for understanding fungal proliferation and host-pathogen interactions.
  • Published in:Current Opinion in Microbiology,
  • Study Type:Review,
  • Source: PMID: 39260180, DOI: 10.1016/j.mib.2024.102539
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