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https://www.arca.fiocruz.br/handle/icict/49826
CRYPTOCOCCUS EXTRACELLULAR VESICLES PROPERTIES AND THEIR USE AS VACCINE PLATFORMS
Author
Rizzo, Juliana
Wong, Sarah SzeWah
Gazi, Anastasia D.
Moyrand, Frédérique
Chaze, Thibault
Commere, Pierre-Henri
Novault, Sophie
Matondo, Mariette
Péhau-Arnaudet, Gérard
Reis, Flavia Coelho Garcia dos
Vos, Matthijn
Alves, Lysangela Ronalte
May, Robin C.
Nimrichter, Leonardo
Rodrigues, Marcio Lourenço
Aimanianda, Vishukumar
Janbon, Guilhem
Wong, Sarah SzeWah
Gazi, Anastasia D.
Moyrand, Frédérique
Chaze, Thibault
Commere, Pierre-Henri
Novault, Sophie
Matondo, Mariette
Péhau-Arnaudet, Gérard
Reis, Flavia Coelho Garcia dos
Vos, Matthijn
Alves, Lysangela Ronalte
May, Robin C.
Nimrichter, Leonardo
Rodrigues, Marcio Lourenço
Aimanianda, Vishukumar
Janbon, Guilhem
Affilliation
Institut Pasteur. Département de Mycologie. Unité Biologie des ARN des Pathogènes Fongiques. Paris, France.
Institut Pasteur. Département de Mycologie. Unité Mycologie Moléculaire. Paris, France.
Institut Pasteur. Département de Biologie Cellulaire et Infection. Ultrastructural Bio-Imaging UTechS UBI. Paris, France.
Institut Pasteur. Département de Mycologie. Unité Biologie des ARN des Pathogènes Fongiques. Paris, France.
Institut Pasteur. Centre de Ressources et Recherches Technologiques. Plateforme Protéomique, Unité de Spectrométrie de Masse pour la Biologie. Paris, France.
Institut Pasteur. Centre de Ressources et Recherches Technologiques. Cytometry and Biomarkers. Paris, France.
Institut Pasteur. Centre de Ressources et Recherches Technologiques. Cytometry and Biomarkers. Paris, France.
Institut Pasteur. Centre de Ressources et Recherches Technologiques. Plateforme Protéomique, Unité de Spectrométrie de Masse pour la Biologie. Paris, France.
Institut Pasteur. Département de Biologie Cellulaire et Infection. Ultrastructural Bio-Imaging UTechS UBI. Paris, France.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. / Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil.
Institut Pasteur. Centre de Ressources et Recherches Technologiques. NanoImaging Core Facility. Paris, France.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
University of Birmingham. Institute of Microbiology and Infection and School of Biosciences. Birmingham, United Kingdom.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. / Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil.
Institut Pasteur. Département de Mycologie. Unité Mycologie Moléculaire. Paris, France.
Institut Pasteur. Département de Mycologie. Unité Biologie des ARN des Pathogènes Fongiques. Paris, France.
Institut Pasteur. Département de Mycologie. Unité Mycologie Moléculaire. Paris, France.
Institut Pasteur. Département de Biologie Cellulaire et Infection. Ultrastructural Bio-Imaging UTechS UBI. Paris, France.
Institut Pasteur. Département de Mycologie. Unité Biologie des ARN des Pathogènes Fongiques. Paris, France.
Institut Pasteur. Centre de Ressources et Recherches Technologiques. Plateforme Protéomique, Unité de Spectrométrie de Masse pour la Biologie. Paris, France.
Institut Pasteur. Centre de Ressources et Recherches Technologiques. Cytometry and Biomarkers. Paris, France.
Institut Pasteur. Centre de Ressources et Recherches Technologiques. Cytometry and Biomarkers. Paris, France.
Institut Pasteur. Centre de Ressources et Recherches Technologiques. Plateforme Protéomique, Unité de Spectrométrie de Masse pour la Biologie. Paris, France.
Institut Pasteur. Département de Biologie Cellulaire et Infection. Ultrastructural Bio-Imaging UTechS UBI. Paris, France.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. / Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil.
Institut Pasteur. Centre de Ressources et Recherches Technologiques. NanoImaging Core Facility. Paris, France.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
University of Birmingham. Institute of Microbiology and Infection and School of Biosciences. Birmingham, United Kingdom.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. / Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil.
Institut Pasteur. Département de Mycologie. Unité Mycologie Moléculaire. Paris, France.
Institut Pasteur. Département de Mycologie. Unité Biologie des ARN des Pathogènes Fongiques. Paris, France.
Abstract
Whereas extracellular vesicle (EV) research has become commonplace in different biomedical fields, this field of research is still in its infancy in mycology. Here we provide a robust set of data regarding the structural and compositional aspects of EVs isolated from the fungal pathogenic species Cryptococcus neoformans, C. deneoformans and C. deuterogattii. Using cutting-edge methodological approaches including cryogenic electron microscopy and cryogenic electron tomography, proteomics, and flow cytometry, we revisited cryptococcal EV features and suggest a new EV structural model, in which the vesicular lipid bilayer is covered by mannoprotein-based fibrillar decoration, bearing the capsule polysaccharide as its outer layer. About 10%
of the EV population is devoid of fibrillar decoration, adding another aspect to EV diversity. By analysing EV protein cargo from the three species, we characterized the typical Cryptococcus EV proteome. It contains several membrane-bound protein families, including some Tsh proteins bearing a SUR7/PalI motif. The presence of known protective antigens on the surface of Cryptococcus EVs, resembling the morphology
of encapsulated virus structures, suggested their potential as a vaccine. Indeed, mice immunized with EVs obtained from an acapsular C. neoformans mutant strain rendered a strong antibody response in mice and significantly prolonged their survival upon C. neoformans infection.
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