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Updated: May 17, 2026

Size Matters: Measurement of Capsule Diameter in Cryptococcus neoformans
Published on: February 27, 2018
Cryptococcus neoformans requires the ESCRT protein Vps23 for iron acquisition from heme, for capsule formation, and
Guanggan Hu1, Mélissa Caza, Brigitte Cadieux
1Michael Smith Laboratories, Department of Microbiology and Immunology, The University of British Columbia, Vancouver, BC, Canada.
Abstract:
Iron availability is a key regulator of virulence factor elaboration in Cryptococcus neoformans, the causative agent of fungal meningoencephalitis in HIV/AIDS patients. In addition, iron is an essential nutrient for pathogen proliferation in mammalian hosts but little is known about the mechanisms of iron sensing and uptake in fungal pathogens that attack humans. In this study, we mutagenized C. neoformans by Agrobacterium-mediated T-DNA insertion and screened for mutants with reduced growth on heme as the sole iron source. Among 34 mutants, we identified a subset with insertions in the gene for the ESCRT-I (endosomal sorting complex required for transport) protein Vps23 that resulted in a growth defect on heme, presumably due to a defect in uptake via endocytosis or misregulation of iron acquisition from heme. Remarkably, vps23 mutants were also defective in the elaboration of the cell-associated capsular polysaccharide that is a major virulence factor, while overexpression of Vps23 resulted in cells with a slightly enlarged capsule. These phenotypes were mirrored by a virulence defect in the vps23 mutant in a mouse model of cryptococcosis and by hypervirulence of the overexpression strain. Overall, these results reveal an important role for trafficking via ESCRT functions in both heme uptake and capsule formation, and they further reinforce the connection between iron and virulence factor deployment in C. neoformans.
Insights
Cryptococcus neoformans iron uptake and capsule formation are regulated by Vps23, an endosomal sorting complex required for transport (ESCRT) protein. This discovery links iron acquisition and virulence in fungal meningitis.
Area of Science:
- Mycology
- Molecular Biology
- Pathogenesis
Background:
- Iron availability critically influences Cryptococcus neoformans virulence, particularly in HIV/AIDS patients.
- Mechanisms of iron sensing and uptake in human fungal pathogens remain poorly understood.
Purpose of the Study:
- To investigate the role of iron acquisition mechanisms in Cryptococcus neoformans.
- To identify genes involved in iron sensing and uptake, focusing on heme utilization.
Main Methods:
- Agrobacterium-mediated T-DNA insertion mutagenesis of C. neoformans.
- Screening for mutants with impaired growth on heme as the sole iron source.
- Analysis of Vps23 gene function in iron uptake and capsule elaboration.
Main Results:
- Mutants with insertions in the Vps23 gene exhibited growth defects on heme, suggesting impaired iron uptake.
- Vps23 mutants showed defects in capsular polysaccharide elaboration, a key virulence factor.
- Vps23 overexpression led to enlarged capsules and altered virulence in a mouse model.
Conclusions:
- The endosomal sorting complex required for transport (ESCRT) protein Vps23 plays a crucial role in heme iron uptake and capsule formation in C. neoformans.
- Vps23 function is essential for regulating the connection between iron availability and virulence factor deployment.
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