Eukaryotic Cell doi:10.1128/EC.00370-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.
Extracellular vesicles produced by Cryptococcus neoformans contain protein components associated with virulence
Marcio L. Rodrigues*,
Ernesto S. Nakayasu,
Debora L. Oliveira,
Leonardo Nimrichter,
Joshua D. Nosanchuk,
Igor C. Almeida,
and
Arturo Casadevall*
Laboratório de Estudos Integrados em Bioquímica Microbiana, Departamento de Microbiologia Geral, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, CEP 21941590, RJ, Brazil; Department of Biological Sciences, The Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX, 79968-0519, USA; Department of Microbiology and Immunology and Division of Infectious Diseases of the Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA
* To whom correspondence should be addressed. Email:
marcio{at}micro.ufrj.br. casadeva{at}aecom.yu.edu.
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Abstract |
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Cryptococcus neoformans produces vesicles containing its major virulence factor, the capsular polysaccharide glucuronoxylomannan (GXM). These vesicles cross the cell wall to reach the extracellular space, where the polysaccharide is supposedly used for capsule growth or delivered into host tissues. In the present study, we characterized vesicle morphology and protein composition by a combination of techniques including electron microscopy, proteomics, enzymatic activity and serological reactivity. The origin and traffic of secretory vesicles in C. neoformans appear to involve cellular exosome-like compartments resembling multi-vesicular bodies. Extracellular vesicles manifested various sizes and morphologies, including electron lucid membrane bodies and electron dense vesicles. Seventy-six proteins were identified by proteomic analysis, including several related to virulence and protection against oxidative stress. Biochemical tests indicated laccase and urease activities in vesicles. In addition, different vesicle proteins were recognized by sera from patients with cryptococcosis. These results reveal an efficient and general mechanism of secretion of pathogenesis-related molecules in C. neoformans, suggesting that these structures function as ‘virulence bags’ that deliver a concentrated payload of fungal products to host effector cells and tissues.
