Eukaryotic Cell MMBR Online 2003
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Eukaryotic Cell, January 2007, p. 48-59, Vol. 6, No. 1
1535-9778/07/$08.00+0     doi:10.1128/EC.00318-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Vesicular Polysaccharide Export in Cryptococcus neoformans Is a Eukaryotic Solution to the Problem of Fungal Trans-Cell Wall Transport{triangledown}

Marcio L. Rodrigues,1,{ddagger} Leonardo Nimrichter,1,{ddagger} Débora L. Oliveira,1,{ddagger} Susana Frases,2 Kildare Miranda,3 Oscar Zaragoza,2,{dagger} Mauricio Alvarez,2 Antonio Nakouzi,2 Marta Feldmesser,2,4 and Arturo Casadevall2,4*

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,1 Department of Microbiology and Immunology,2 and Division of Infectious Diseases,4 of the Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, New York 10461; and Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941590, Brazil3

Received 6 October 2006/ Accepted 6 November 2006

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.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461. Phone: (718) 430-2215. Fax: (718) 430-8968. E-mail: casadeva{at}aecom.yu.edu.

{triangledown} Published ahead of print on 17 November 2006.

{ddagger} M.L.R., L.N., and D.L.O. contributed equally to this work.

{dagger} Present address: Servicio de Micología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra Majadahonda-Pozuelo km 2, 28220 Majadahonda, Madrid, Spain.

Eukaryotic Cell, January 2007, p. 48-59, Vol. 6, No. 1
1535-9778/07/$08.00+0     doi:10.1128/EC.00318-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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