Cryptococcal cell morphology affects host cell interactions and pathogenicity
Open accessAbstract
Cryptococcus neoformans is a common life-threatening human fungal pathogen. The size of cryptococcal cells is typically 5 to 10 microm. Cell enlargement was observed in vivo, producing cells up to 100 microm. These morphological changes in cell size affected pathogenicity via reducing phagocytosis by host mononuclear cells, increasing resistance to oxidative and nitrosative stress, and correlated with reduced penetration of the central nervous system. Cell enlargement was stimulated by coinfection with strains of opposite mating type, and ste3aDelta pheromone receptor mutant strains had reduced cell enlargement. Finally, analysis of DNA content in this novel cell type revealed that these enlarged cells were polyploid, uninucleate, and produced daughter cells in vivo. These results describe a novel mechanism by which C. neoformans evades host phagocytosis to allow survival of a subset of the population at early stages of infection. Thus, morphological changes play unique and specialized roles during infection.
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Unique to C. neoformans, the cell cycle is differentially regulated during the formation of polyploid titan cells, which are gigantic cells that form inside host lungs and play important roles in pathogenesis, stress responses, and drug tolerance.
“Unique to C. neoformans, the cell cycle is differentially regulated during the formation of polyploid titan cells, which are gigantic cells that form inside host lungs and play important roles in pathogenesis, stress responses, and drug tolerance (Okagaki et al. 2010; Zaragoza et al. 2010).”
From Genetic analysis of Hsp90 function in <i>Cryptococcus neoformans</i> highlights key roles in stress tolerance and virulence (2022) · cites this paper as Okagaki et al. 2010
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References 78 · Cited by 345
- Authors
- Okagaki, L. H., Strain, A. K., Nielsen, J. N., Charlier, C., Baltes, N. J., Chrétien, F., Heitman, J., Dromer, F., & Nielsen, K.
- Affiliations
- University of Minnesota (US)
- University of North Carolina at Chapel Hill (US)
- Centre National de la Recherche Scientifique (FR)
- Duke University (US)
- Corresponding author
- Nielsen, Kirsten
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-06-17
- Volume
- 6
- Issue
- 6
- Pages
- e1000953
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC2887476
- OpenAlex
- W2055416073
- Cited by
- 345
- References
- 78
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 19 · 2023: 18 · 2022: 23 · 2021: 21 · 2020: 15 · 2019: 19 · 2018: 26 · 2017: 29 · 2016: 22 · 2015: 24 · 2014: 23 · 2013: 21 · 2012: 33
- FWCI
- 20.48
- Type
- journal article
- Language
- en
- Update notices
- correction (2010-06-23)
- Open access
- gold
- doi.org
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DukeSpace (Duke University) (submittedVersion, cc-by-nc-nd)
- Figshare (submittedVersion, cc-by)
- Funders
- University of Minnesota
- National Institutes of Health (2r01ai050113-16a1)
- National Institute of Allergy and Infectious Diseases (AI052080, R01 AI50113, AI50113, R01AI080275, R01-AI050113, AI070152, K22AI070152, T32AI052080)
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- Cryptococcus neoformans, cell expansion, cell morphology, pathogenicity, phagocytosis evasion, oxidative stress resistance, CNS penetration, polyploidy, host-pathogen interaction, fungal virulence
- MeSH terms
- Animals, Blood-Brain Barrier, Brain, Cell Adhesion, Cryptococcosis, Cryptococcus neoformans, Female, Flow Cytometry, Humans, Lung Diseases, Fungal, Mice, Inbred A, Phagocytosis, Ploidies, RNA, Messenger, Blotting, Western, Oxidative Stress, Bronchoalveolar Lavage, Reverse Transcriptase Polymerase Chain Reaction, Receptors, Pheromone, Cell Proliferation, Mice
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