title: Vesicular polysaccharide export in Cryptococcus neoformans is a eukaryotic solution to the problem of fungal trans-cell wall transport.
abstract: The mechanisms by which macromolecules are transported through the cell wall of fungi are not known. A central question in the biology of Cryptococcus neoformans, the causative agent of cryptococcosis, is the mechanism by which capsular polysaccharide synthesized inside the cell is exported to the extracellular environment for capsule assembly and release. We demonstrate that C. neoformans produces extracellular vesicles during in vitro growth and animal infection. Vesicular compartments, which are transferred to the extracellular space by cell wall passage, contain glucuronoxylomannan (GXM), a component of the cryptococcal capsule, and key lipids, such as glucosylceramide and sterols. A correlation between GXM-containing vesicles and capsule expression was observed. The results imply a novel mechanism for the release of the major virulence factor of C. neoformans whereby polysaccharide packaged in lipid vesicles crosses the cell wall and the capsule network to reach the extracellular environment.
authors.affiliation: Laboratório de Estudos Integrados em Bioquímica Microbiana, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941590, Brazil.
authors.forename: Marcio L
authors.initials: ML
authors.lastname: Rodrigues
authors.forename: Leonardo
authors.initials: L
authors.lastname: Nimrichter
authors.forename: Débora L
authors.initials: DL
authors.lastname: Oliveira
authors.forename: Susana
authors.initials: S
authors.lastname: Frases
authors.forename: Kildare
authors.initials: K
authors.lastname: Miranda
authors.forename: Oscar
authors.initials: O
authors.lastname: Zaragoza
authors.forename: Mauricio
authors.initials: M
authors.lastname: Alvarez
authors.forename: Antonio
authors.initials: A
authors.lastname: Nakouzi
authors.forename: Marta
authors.initials: M
authors.lastname: Feldmesser
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
mesh_terms: D000818:Animals; D016667:Bacterial Capsules / Q000096:biosynthesis; D001692:Biological Transport; D002460:Cell Line; D002473:Cell Wall / Q000378:metabolism*; D002499:Centrifugation, Density Gradient; D003455:Cryptococcus neoformans / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D005963:Glucosylceramides / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D011134:Polysaccharides / Q000378:metabolism; D011135:Polysaccharides, Bacterial / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism*; D013261:Sterols / Q000378:metabolism
chemical_list: D005963:Glucosylceramides; D011134:Polysaccharides; D011135:Polysaccharides, Bacterial; D013261:Sterols; C027478:glucuronoxylomannan