{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T14:54:29Z","timestamp":1783349669137,"version":"3.54.6"},"posted":{"date-parts":[[2026,4,15]]},"group-title":"Biochemistry","reference-count":68,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                  and\n                  <jats:italic>Cryptococcus gattii<\/jats:italic>\n                  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 analyzed 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\n                  <jats:italic>C. neoformans<\/jats:italic>\n                  . Solid-state NMR revealed that aggregated \u03b1-1,3-glucans form the principal rigid domain of the cell wall in both species and are closely associated with chitin microfibrils, whereas surrounding \u03b2-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\n                  <jats:italic>C. neoformans<\/jats:italic>\n                  , chitosan depletion increased \u03b1-1,3-glucan content and reduced \u03b2-glucan levels, whereas\n                  <jats:italic>C. gattii<\/jats:italic>\n                  selectively lost one \u03b1-1,3-glucan subtype while maintaining \u03b2-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\n                  <jats:italic>Cryptococcus<\/jats:italic>\n                  species.\n                <\/jats:p>","DOI":"10.64898\/2026.04.14.718415","type":"posted-content","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T04:40:13Z","timestamp":1776314413000},"source":"Crossref","is-referenced-by-count":1,"title":["Molecular Architecture of\n                  <i>Cryptococcus<\/i>\n                  Cell Walls Reveals Species-Specific Chitosan-Dependent Remodeling"],"prefix":"10.64898","author":[{"given":"Ankur","family":"Ankur","sequence":"first","affiliation":[{"name":"Department of Chemistry, Michigan State University, East Lansing, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajendra","family":"Upadhya","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahsa","family":"Doosti","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Michigan State University, East Lansing, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davis","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Pathology, Duke University School of Medicine, Durham, NC, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Michigan State University, East Lansing, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Hung","sequence":"additional","affiliation":[{"name":"National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer K.","family":"Lodge","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Michigan State University, East Lansing, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041811300864000_2026.04.14.718415v1.1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.8.4.515"},{"key":"2026041811300864000_2026.04.14.718415v1.2","doi-asserted-by":"crossref","first-page":"282","DOI":"10.3390\/jof7040282","article-title":"Cryptococcus neoformans and Cryptococcus gattii species complexes in Latin America: a map of molecular types, genotypic diversity, and antifungal susceptibility as reported by the Latin American Cryptococcal Study Group","volume":"7","year":"2021","journal-title":"J. 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