Comparative Molecular and Immunoregulatory Analysis of Extracellular Vesicles from Candida albicans and Candida auris
Abstract
Candida auris is a recently described multidrug-resistant pathogenic fungus that is increasingly responsible for health care-associated outbreaks across the world. Bloodstream infections of this fungus cause death in up to 70% of cases. Aggravating this scenario, the disease-promoting mechanisms of C. auris are poorly understood. Fungi release extracellular vesicles (EVs) that carry a broad range of molecules, including proteins, lipids, carbohydrates, pigments, and RNA, many of which are virulence factors. Here, we carried out a comparative molecular characterization of C. auris and Candida albicans EVs and evaluated their capacity to modulate effector mechanisms of host immune defense. Using proteomics, lipidomics, and transcriptomics, we found that C. auris released EVs with payloads that were significantly different from those of EVs released by C. albicans. EVs released by C. auris potentiated the adhesion of this yeast to an epithelial cell monolayer, while EVs from C. albicans had no effect. C. albicans EVs primed macrophages for enhanced intracellular yeast killing, whereas C. auris EVs promoted survival of the fungal cells. Moreover, EVs from both C. auris and C. albicans induced the activation of bone marrow-derived dendritic cells. Together, our findings show distinct profiles and properties of EVs released by C. auris and bymore »
- Authors:
-
[1];
[2];
[3];
[4];
[5];
[3];
[6];
[2];
- Albert Einstein College of Medicine, Bronx, NY (United States)
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (United States)
- Carlos Chagas Inst., Curitiba (Brazil); Federal Univ. of Rio de Janeiro (Brazil)
- Federal Univ. of Rio de Janeiro (Brazil)
- Carlos Chagas Inst., Curitiba (Brazil)
- Publication Date:
- Research Org.:
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1823085
- Report Number(s):
- PNNL-SA-156740
Journal ID: ISSN 2379-5077
- Grant/Contract Number:
- AC05-76RL01830
- Resource Type:
- Accepted Manuscript
- Journal Name:
- mSystems
- Additional Journal Information:
- Journal Volume: 6; Journal Issue: 4; Journal ID: ISSN 2379-5077
- Publisher:
- American Society for Microbiology
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Candida auris; Candida albicans; extracellular vesicles; multi-omics; fungal pathogenesis; candidiasis
Citation Formats
Zamith-Miranda, Daniel, Heyman, Heino M., Couvillion, Sneha P., Cordero, Radames B., Rodrigues, Marcio L., Nimrichter, Leonardo, Casadevall, Arturo, Amatuzzi, Rafaela F., Alves, Lysangela R., Nakayasu, Ernesto S., and Nosanchuk, Joshua D. Comparative Molecular and Immunoregulatory Analysis of Extracellular Vesicles from Candida albicans and Candida auris. United States: N. p., 2021.
Web. doi:10.1128/msystems.00822-21.
Zamith-Miranda, Daniel, Heyman, Heino M., Couvillion, Sneha P., Cordero, Radames B., Rodrigues, Marcio L., Nimrichter, Leonardo, Casadevall, Arturo, Amatuzzi, Rafaela F., Alves, Lysangela R., Nakayasu, Ernesto S., & Nosanchuk, Joshua D. Comparative Molecular and Immunoregulatory Analysis of Extracellular Vesicles from Candida albicans and Candida auris. United States. https://doi.org/10.1128/msystems.00822-21
Zamith-Miranda, Daniel, Heyman, Heino M., Couvillion, Sneha P., Cordero, Radames B., Rodrigues, Marcio L., Nimrichter, Leonardo, Casadevall, Arturo, Amatuzzi, Rafaela F., Alves, Lysangela R., Nakayasu, Ernesto S., and Nosanchuk, Joshua D. Tue .
"Comparative Molecular and Immunoregulatory Analysis of Extracellular Vesicles from Candida albicans and Candida auris". United States. https://doi.org/10.1128/msystems.00822-21. https://www.osti.gov/servlets/purl/1823085.
@article{osti_1823085,
title = {Comparative Molecular and Immunoregulatory Analysis of Extracellular Vesicles from Candida albicans and Candida auris},
author = {Zamith-Miranda, Daniel and Heyman, Heino M. and Couvillion, Sneha P. and Cordero, Radames B. and Rodrigues, Marcio L. and Nimrichter, Leonardo and Casadevall, Arturo and Amatuzzi, Rafaela F. and Alves, Lysangela R. and Nakayasu, Ernesto S. and Nosanchuk, Joshua D.},
abstractNote = {Candida auris is a recently described multidrug-resistant pathogenic fungus that is increasingly responsible for health care-associated outbreaks across the world. Bloodstream infections of this fungus cause death in up to 70% of cases. Aggravating this scenario, the disease-promoting mechanisms of C. auris are poorly understood. Fungi release extracellular vesicles (EVs) that carry a broad range of molecules, including proteins, lipids, carbohydrates, pigments, and RNA, many of which are virulence factors. Here, we carried out a comparative molecular characterization of C. auris and Candida albicans EVs and evaluated their capacity to modulate effector mechanisms of host immune defense. Using proteomics, lipidomics, and transcriptomics, we found that C. auris released EVs with payloads that were significantly different from those of EVs released by C. albicans. EVs released by C. auris potentiated the adhesion of this yeast to an epithelial cell monolayer, while EVs from C. albicans had no effect. C. albicans EVs primed macrophages for enhanced intracellular yeast killing, whereas C. auris EVs promoted survival of the fungal cells. Moreover, EVs from both C. auris and C. albicans induced the activation of bone marrow-derived dendritic cells. Together, our findings show distinct profiles and properties of EVs released by C. auris and by C. albicans and highlight the potential contribution of C. auris EVs to the pathogenesis of this emerging pathogen.},
doi = {10.1128/msystems.00822-21},
journal = {mSystems},
number = 4,
volume = 6,
place = {United States},
year = {Tue Aug 24 00:00:00 EDT 2021},
month = {Tue Aug 24 00:00:00 EDT 2021}
}
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