TY - JOUR
T1 - Comparative molecular and immunoregulatory analysis of extracellular vesicles from candida albicans and candida auris
AU - Zamith-Miranda, Daniel
AU - Heyman, Heino M.
AU - Couvillion, Sneha P.
AU - Cordero, Radames J.B.
AU - Rodrigues, Marcio L.
AU - Nimrichter, Leonardo
AU - Casadevall, Arturo
AU - Amatuzzi, Rafaela F.
AU - Alves, Lysangela R.
AU - Nakayasu, Ernesto S.
AU - Nosanchuk, Joshua D.
N1 - Funding Information:
D.Z.M., J.D.N., and E.S.N. were supported by National Institutes of Health (NIH)- National Institute of Allergy and Infectious Diseases grant R21 AI124797. L.N. was supported by grants from the Brazilian agency Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; grants 311179/2017-7 and 408711/2017-7) and FAPERJ (E-26/202.809/2018). M.L.R. was supported by grants from the Brazilian Ministry of Health (grant 440015/2018-9), Conselho Nacional de Desenvolvimento Científico e Tecnológico (grants 405520/2018-2 and 301304/2017-3), and Fiocruz (grants PROEP-ICC 442186/2019-3, VPPCB-007-FIO-18, and VPPIS-001-FIO18). M.L.R. also acknowledges support from the Instituto Nacional de Ciência e Tecnologia de Inovação em Doenças de Populações Negligenciadas (INCT-IDPN). A.C. was supported in part by NIH grants AI052733, AI15207, and HL059842. We thank the Johns Hopkins University School of Medicine Microscope Facility for the transmission electron microscopy (TEM) of EVs. Parts of this work were performed in the Environmental Molecular Science Laboratory, a U.S. Department of Energy (DOE) national scientific user facility at PNNL in Richland,WA.
Funding Information:
D.Z.M., J.D.N., and E.S.N. were supported by National Institutes of Health (NIH)– National Institute of Allergy and Infectious Diseases grant R21 AI124797. L.N. was supported by grants from the Brazilian agency Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; grants 311179/2017-7 and 408711/2017-7) and FAPERJ (E-26/202.809/2018). M.L.R. was supported by grants from the Brazilian Ministry of Health (grant 440015/2018-9), Conselho Nacional de Desenvolvimento Científico e Tecnológico (grants 405520/2018-2 and 301304/2017-3), and Fiocruz (grants PROEP-ICC 442186/2019-3, VPPCB-007-FIO-18, and VPPIS-001-FIO18). M.L.R. also acknowledges support from the Instituto Nacional de Ciência e Tecnologia de Inovação em Doenças de Populações Negligenciadas (INCT-IDPN). A.C. was supported in part by NIH grants AI052733, AI15207, and HL059842.
Publisher Copyright:
© 2021 Zamith-Miranda et al.
PY - 2021/7
Y1 - 2021/7
N2 - 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. IMPORTANCE Candida auris is a recently described multidrug-resistant pathogenic fungus that is responsible for outbreaks across the globe, particularly in the context of nosocomial infections. Its virulence factors and pathogenesis are poorly understood. Here, we tested the hypothesis that extracellular vesicles (EVs) released by C. auris are a disease-promoting factor. We describe the production of EVs by C. auris and compare their biological activities against those of the better- characterized EVs from C. albicans. C. auris EVs have immunoregulatory properties, of which some are opposite those of C. albicans EVs. We also explored the cargo and structural components of those vesicles and found that they are remarkably distinct compared to EVs from C. auris's phylogenetic relative Candida albicans.
AB - 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. IMPORTANCE Candida auris is a recently described multidrug-resistant pathogenic fungus that is responsible for outbreaks across the globe, particularly in the context of nosocomial infections. Its virulence factors and pathogenesis are poorly understood. Here, we tested the hypothesis that extracellular vesicles (EVs) released by C. auris are a disease-promoting factor. We describe the production of EVs by C. auris and compare their biological activities against those of the better- characterized EVs from C. albicans. C. auris EVs have immunoregulatory properties, of which some are opposite those of C. albicans EVs. We also explored the cargo and structural components of those vesicles and found that they are remarkably distinct compared to EVs from C. auris's phylogenetic relative Candida albicans.
KW - Candida albicans
KW - Candida auris
KW - Candidiasis
KW - Extracellular vesicles
KW - Fungal pathogenesis
KW - Multi-omics
UR - http://www.scopus.com/inward/record.url?scp=85113433494&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85113433494&partnerID=8YFLogxK
U2 - 10.1128/mSystems.00822-21
DO - 10.1128/mSystems.00822-21
M3 - Article
C2 - 34427507
AN - SCOPUS:85113433494
SN - 2379-5077
VL - 6
JO - mSystems
JF - mSystems
IS - 4
M1 - e00822-21
ER -