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Molecular architecture of Cryptococcus cell walls reveals species-specific chitosan-dependent remodeling - Nature

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AbstractCryptococcus 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.

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AcknowledgementsWe thank Yukiko Banzai, Yuko Ishiyama, Asami Ogawa, and Yingda Xiao of the University of Tokyo for their assistance with animal experiments and laboratory work. We are grateful to Yuriko Sakamaki of the Ochanomizu Research Facility, Institute of Science Tokyo, for her technical support with electron microscopy sample preparation and imaging. FundingThis work was supported by Grants-in-Aid for Scientific Research, Japan [grant Nos. 24K19023 to S. B. and 22K08174 to H. T.]; Sakakibara Heart Foundation Cardiovascular Research Program 2023 (to S. B.); Japan Foundation for Applied Enzymology (to S. B.). I. K. was supported by a Grant-in-Aid for Scientific Research (S) of the Japan Society for the Promotion of Science and by the Japan Agency for Medical Research, Development (JP20ek0210152, JP18gm6210010, JP20ek0210141, JP20ek0109440, JP20ek0109487, JP17gm0810013, JP18km0405209, JP21ek0109543, JP21ek0109569, JP21tm0724601, JP22ama121016, JP22ek0210172, JP22ek0210167, JP22bm1123011). Author informationAuthor notesThese authors contributed equally: Satoshi Bujo, Takayuki Fujiwara, Masayuki Kubota.

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