Molecular architecture of Cryptococcus cell walls reveals species-specific chitosan-dependent remodeling
Abstract
Cryptococcus neoformans and Cryptococcus gattii are fungal pathogens that cause life-threatening infections, including cryptococcal meningitis. A distinctive feature of the cryptococcal cell wall is the extensive deacetylation of chitin to chitosan, a modification that is essential for virulence but whose structural role in cell-wall organization remains poorly understood. Here, we analyze the cell walls of wild-type strains of both species and their avirulent chitosan-deficient mutants, which serve as vaccine candidates. Loss of chitosan disrupted cell morphology and altered cell-wall ultrastructure, with more pronounced defects in C. neoformans . Solid-state NMR reveals that aggregated α-(1→3)-glucans form the principal rigid domain of the cell wall in both species and are closely associated with chitin microfibrils, whereas surrounding β-glucans and mannoproteins constitute a more dynamic matrix. Chitosan modulates hydration and flexibility, and its loss increases chitin exposure and triggers species-specific remodeling of the polysaccharide network. In C. neoformans , chitosan depletion increased α-(1→3)-glucan content and reduced β-glucan levels, whereas C. gattii selectively lost one α-(1→3)-glucan subtype while maintaining β-glucan levels. Although capsule production remained intact, chitosan deficiency altered glucuronoxylomannan linkage patterns and mannoprotein composition. These findings reveal how chitosan organizes cryptococcal cell-wall architecture and highlight distinct structural adaptation strategies among pathogenic Cryptococcus species.
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BibTeX
@article{ankur2026molecular,
title = {{Molecular architecture of Cryptococcus cell walls reveals species-specific chitosan-dependent remodeling}},
author = {Ankur Ankur and Rajendra Upadhya and Mahsa Doosti and Davis Ferreira and Sara E. Miller and Li Xie and Ivan Hung and Jennifer K. Lodge and Tuo Wang},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78940-9},
url = {https://www.nature.com/articles/s41467-026-78940-9},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Molecular architecture of Cryptococcus cell walls reveals species-specific chitosan-dependent remodeling
AU - Ankur Ankur
AU - Rajendra Upadhya
AU - Mahsa Doosti
AU - Davis Ferreira
AU - Sara E. Miller
AU - Li Xie
AU - Ivan Hung
AU - Jennifer K. Lodge
AU - Tuo Wang
PY - 2026
DA - 2026/10/18
JO - Nature Communications
DO - 10.1038/s41467-026-78940-9
UR - https://www.nature.com/articles/s41467-026-78940-9
AB - Cryptococcus neoformans and Cryptococcus gattii are fungal pathogens that cause life-threatening infections, including cryptococcal meningitis. A distinctive feature of the cryptococcal cell wall is the extensive deacetylation of chitin to chitosan, a modification that is essential for virulence but whose structural role in cell-wall organization remains poorly understood. Here, we analyze the cell walls of wild-type strains of both species and their avirulent chitosan-deficient mutants, which serve as vaccine candidates. Loss of chitosan disrupted cell morphology and altered cell-wall ultrastructure, with more pronounced defects in C. neoformans . Solid-state NMR reveals that aggregated α-(1→3)-glucans form the principal rigid domain of the cell wall in both species and are closely associated with chitin microfibrils, whereas surrounding β-glucans and mannoproteins constitute a more dynamic matrix. Chitosan modulates hydration and flexibility, and its loss increases chitin exposure and triggers species-specific remodeling of the polysaccharide network. In C. neoformans , chitosan depletion increased α-(1→3)-glucan content and reduced β-glucan levels, whereas C. gattii selectively lost one α-(1→3)-glucan subtype while maintaining β-glucan levels. Although capsule production remained intact, chitosan deficiency altered glucuronoxylomannan linkage patterns and mannoprotein composition. These findings reveal how chitosan organizes cryptococcal cell-wall architecture and highlight distinct structural adaptation strategies among pathogenic Cryptococcus species.
SN - 2041-1723
ER -