Eukaryotic Cell
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EC Accepts, published online ahead of print on 17 November 2006
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Eukaryotic Cell doi:10.1128/EC.00318-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Vesicular polysaccharide export in Cryptococcus neoformans is an eukaryotic solution to the problem of fungal trans-cell wall transport

Marcio L. Rodrigues, Leonardo Nimrichter, Débora L. Oliveira, Susana Frases, Kildare Miranda, Oscar Zaragoza, Mauricio Alvarez, Antonio Nakouzi, Marta Feldmesser, and Arturo Casadevall*

Laboratório de Estudos Integrados em Bioquímica Microbiana, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, 21941590, Brazil; Department of Microbiology and Immunology and the Division of Infectious Diseases of the Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY USA 10461; Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941590, Brazil

* To whom correspondence should be addressed. Email: casadeva{at}aecom.yu.edu.


   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.




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