Comparative Molecular and Immunoregulatory Analysis of Extracellular Vesicles from Candida albicans and Candida auris

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.

doi:10.1128/msystems.00822-21

Title: Comparative Molecular and Immunoregulatory Analysis of Extracellular Vesicles from Candida albicans and Candida auris

Journal Article · Tue Aug 24 00:00:00 EDT 2021 · mSystems

DOI:https://doi.org/10.1128/msystems.00822-21· OSTI ID:1823085

^[1];

^[2]; Couvillion, Sneha P. ^[2];

^[3];

^[4];

^[5];

^[3]; Amatuzzi, Rafaela F. ^[6];

^[6];

^[2]; Nosanchuk, Joshua D. ^[3]

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)

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.

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Research Organization:: Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1823085

Report Number(s):: PNNL-SA-156740

Journal Information:: mSystems, Vol. 6, Issue 4; ISSN 2379-5077

Publisher:: American Society for MicrobiologyCopyright Statement

Country of Publication:: United States

Language:: English

References (65)

LIQUID: an-open source software for identifying lipids in LC-MS/MS-based lipidomics data Kyle, Jennifer E.; Crowell, Kevin L.; Casey, Cameron P. Bioinformatics, Vol. 33, Issue 11 https://doi.org/10.1093/bioinformatics/btx046	journal	January 2017
An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow Lutz, Manfred B.; Kukutsch, Nicole; Ogilvie, Alexandra L. J. Journal of Immunological Methods, Vol. 223, Issue 1 https://doi.org/10.1016/S0022-1759(98)00204-X	journal	February 1999
Complex heatmaps reveal patterns and correlations in multidimensional genomic data Gu, Zuguang; Eils, Roland; Schlesner, Matthias Bioinformatics, Vol. 32, Issue 18 https://doi.org/10.1093/bioinformatics/btw313	journal	May 2016
Evaluation of chemotherapeutic and cancer-protective properties of sphingosine and C2-ceramide in a human breast stem cell derived carcinogenesis model Ahn, Eun Hyun; Yang, Hong; Hsieh, Ching-Yi International Journal of Oncology https://doi.org/10.3892/ijo.2018.4641	journal	November 2018
The Pathogenic Fungus Paracoccidioides brasiliensis Exports Extracellular Vesicles Containing Highly Immunogenic α-Galactosyl Epitopes Vallejo, Milene C.; Matsuo, Alisson L.; Ganiko, Luciane Eukaryotic Cell, Vol. 10, Issue 3 https://doi.org/10.1128/EC.00227-10	journal	January 2011
Comparison of the RNA Content of Extracellular Vesicles Derived from Paracoccidioides brasiliensis and Paracoccidioides lutzii Peres da Silva, Roberta; Longo, Larissa G. V.; Cunha, Julia P. C. da Cells, Vol. 8, Issue 7 https://doi.org/10.3390/cells8070765	journal	July 2019
Global quantification of mammalian gene expression control Schwanhäusser, Björn; Busse, Dorothea; Li, Na Nature, Vol. 473, Issue 7347 https://doi.org/10.1038/nature10098	journal	May 2011
The PRIDE database and related tools and resources in 2019: improving support for quantification data Perez-Riverol, Yasset; Csordas, Attila; Bai, Jingwen Nucleic Acids Research, Vol. 47, Issue D1 https://doi.org/10.1093/nar/gky1106	journal	November 2018
Compositional and immunobiological analyses of extracellular vesicles released by C andida albicans : Extracellular vesicles from Vargas, Gabriele; Rocha, Juliana D. B.; Oliveira, Debora Leite Cellular Microbiology, Vol. 17, Issue 3 https://doi.org/10.1111/cmi.12374	journal	November 2014
Nanovesicles from Malassezia sympodialis and Host Exosomes Induce Cytokine Responses – Novel Mechanisms for Host-Microbe Interactions in Atopic Eczema Gehrmann, Ulf; Qazi, Khaleda Rahman; Johansson, Catharina PLoS ONE, Vol. 6, Issue 7 https://doi.org/10.1371/journal.pone.0021480	journal	July 2011
The Epidemiology and Prevention of Candida auris Snyder, Graham M.; Wright, Sharon B. Current Infectious Disease Reports, Vol. 21, Issue 6 https://doi.org/10.1007/s11908-019-0675-8	journal	May 2019
MPLEx: a Robust and Universal Protocol for Single-Sample Integrative Proteomic, Metabolomic, and Lipidomic Analyses Nakayasu, Ernesto S.; Nicora, Carrie D.; Sims, Amy C. mSystems, Vol. 1, Issue 3 https://doi.org/10.1128/mSystems.00043-16	journal	May 2016
Vesicular transport in Histoplasma capsulatum : an effective mechanism for trans-cell wall transfer of proteins and lipids in ascomycetes Albuquerque, Priscila Costa; Nakayasu, Ernesto S.; Rodrigues, Marcio L. Cellular Microbiology, Vol. 10, Issue 8 https://doi.org/10.1111/j.1462-5822.2008.01160.x	journal	August 2008
Listeria monocytogenes virulence factors, including listeriolysin O, are secreted in biologically active extracellular vesicles Coelho, Carolina; Brown, Lisa; Maryam, Maria Journal of Biological Chemistry, Vol. 294, Issue 4 https://doi.org/10.1074/jbc.RA118.006472	journal	November 2018
Extracellular Vesicles Produced by Cryptococcus neoformans Contain Protein Components Associated with Virulence Rodrigues, Marcio L.; Nakayasu, Ernesto S.; Oliveira, Debora L. Eukaryotic Cell, Vol. 7, Issue 1 https://doi.org/10.1128/EC.00370-07	journal	November 2007
Global epidemiology of emerging Candida auris Rhodes, Johanna; Fisher, Matthew C. Current Opinion in Microbiology, Vol. 52 https://doi.org/10.1016/j.mib.2019.05.008	journal	December 2019
On the Emergence of Candida auris : Climate Change, Azoles, Swamps, and Birds Casadevall, Arturo; Kontoyiannis, Dimitrios P.; Robert, Vincent mBio, Vol. 10, Issue 4 https://doi.org/10.1128/mBio.01397-19	journal	July 2019
MZmine 2: Modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data Pluskal, Tomáš; Castillo, Sandra; Villar-Briones, Alejandro BMC Bioinformatics, Vol. 11, Issue 1 https://doi.org/10.1186/1471-2105-11-395	journal	July 2010
Pathogen-derived extracellular vesicles mediate virulence in the fatal human pathogen Cryptococcus gattii Bielska, Ewa; Sisquella, Marta Arch; Aldeieg, Maha Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-018-03991-6	journal	April 2018
Antibody Binding Alters the Characteristics and Contents of Extracellular Vesicles Released by Histoplasma capsulatum Matos Baltazar, Ludmila; Nakayasu, Ernesto S.; Sobreira, Tiago J. P. mSphere, Vol. 1, Issue 2 https://doi.org/10.1128/mSphere.00085-15	journal	March 2016
Candida albicans: The Ability to Invade Epithelial Cells and Survive under Oxidative Stress Is Unlinked to Hyphal Length Maza, Paloma K.; Bonfim-Melo, Alexis; Padovan, Ana C. B. Frontiers in Microbiology, Vol. 8 https://doi.org/10.3389/fmicb.2017.01235	journal	July 2017
Extracellular Vesicles from Cryptococcus neoformans Modulate Macrophage Functions Oliveira, D. L.; Freire-de-Lima, C. G.; Nosanchuk, J. D. Infection and Immunity, Vol. 78, Issue 4 https://doi.org/10.1128/IAI.01171-09	journal	February 2010
Immunity to fungal infections Romani, Luigina Nature Reviews Immunology, Vol. 11, Issue 4 https://doi.org/10.1038/nri2939	journal	March 2011
MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification Cox, Jürgen; Mann, Matthias Nature Biotechnology, Vol. 26, Issue 12 https://doi.org/10.1038/nbt.1511	journal	November 2008
Traveling into Outer Space: Unanswered Questions about Fungal Extracellular Vesicles Rodrigues, Marcio L.; Godinho, Rodrigo M. C.; Zamith-Miranda, Daniel PLOS Pathogens, Vol. 11, Issue 12 https://doi.org/10.1371/journal.ppat.1005240	journal	December 2015
Phospholipases play multiple cellular roles including growth, stress tolerance, sexual development, and virulence in fungi Barman, Ananya; Gohain, Dibakar; Bora, Utpal Microbiological Research, Vol. 209 https://doi.org/10.1016/j.micres.2017.12.012	journal	April 2018
RNA in extracellular vesicles: RNA in extracellular vesicles Kim, Kyoung Mi; Abdelmohsen, Kotb; Mustapic, Maja Wiley Interdisciplinary Reviews: RNA, Vol. 8, Issue 4 https://doi.org/10.1002/wrna.1413	journal	January 2017
Cryptococcus neoformans-Derived Microvesicles Enhance the Pathogenesis of Fungal Brain Infection Huang, Sheng-He; Wu, Chun-Hua; Chang, Yun C. PLoS ONE, Vol. 7, Issue 11 https://doi.org/10.1371/journal.pone.0048570	journal	November 2012
Lysophosphatidylcholine exacerbates Leishmania major-dendritic cell infection through interleukin-10 and a burst in arginase1 and indoleamine 2,3-dioxygenase activities Tounsi, Nabila; Meghari, Soraya; Moser, Muriel International Immunopharmacology, Vol. 25, Issue 1 https://doi.org/10.1016/j.intimp.2015.01.006	journal	March 2015
Extracellular vesicles from Paracoccidioides brasiliensis induced M1 polarization in vitro da Silva, Thiago Aparecido; Roque-Barreira, Maria Cristina; Casadevall, Arturo Scientific Reports, Vol. 6, Issue 1 https://doi.org/10.1038/srep35867	journal	October 2016
Protective effect of fungal extracellular vesicles against murine candidiasis Vargas, Gabriele; Honorato, Leandro; Guimarães, Allan Jefferson Cellular Microbiology, Vol. 22, Issue 10 https://doi.org/10.1111/cmi.13238	journal	July 2020
Galectin-3 impacts Cryptococcus neoformans infection through direct antifungal effects Almeida, Fausto; Wolf, Julie M.; da Silva, Thiago Aparecido Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/s41467-017-02126-7	journal	December 2017
Small RNAs derived from tRNAs and rRNAs are highly enriched in exosomes from both old and new world Leishmania providing evidence for conserved exosomal RNA Packaging Lambertz, Ulrike; Oviedo Ovando, Mariana E.; Vasconcelos, Elton JR BMC Genomics, Vol. 16, Issue 1 https://doi.org/10.1186/s12864-015-1260-7	journal	March 2015
Glucosylceramide synthase is an essential regulator of pathogenicity of Cryptococcus neoformans Rittershaus, P. C. Journal of Clinical Investigation, Vol. 116, Issue 6 https://doi.org/10.1172/JCI27890	journal	June 2006
Extracellular vesicles shed by Trypanosoma cruzi are linked to small RNA pathways, life cycle regulation, and susceptibility to infection of mammalian cells Garcia-Silva, Maria R.; Cura das Neves, Roberta Ferreira; Cabrera-Cabrera, Florencia Parasitology Research, Vol. 113, Issue 1 https://doi.org/10.1007/s00436-013-3655-1	journal	November 2013
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources Huang, Da Wei; Sherman, Brad T.; Lempicki, Richard A. Nature Protocols, Vol. 4, Issue 1 https://doi.org/10.1038/nprot.2008.211	journal	December 2008
Gene Expression Changes Induced by Trypanosoma cruzi Shed Microvesicles in Mammalian Host Cells: Relevance of tRNA-Derived Halves Garcia-Silva, Maria R.; Cabrera-Cabrera, Florencia; Cura das Neves, Roberta Ferreira BioMed Research International, Vol. 2014 https://doi.org/10.1155/2014/305239	journal	January 2014
Vesicular Polysaccharide Export in Cryptococcus neoformans Is a Eukaryotic Solution to the Problem of Fungal Trans-Cell Wall Transport Rodrigues, Marcio L.; Nimrichter, Leonardo; Oliveira, Débora L. Eukaryotic Cell, Vol. 6, Issue 1 https://doi.org/10.1128/EC.00318-06	journal	November 2006
Candida albicans- epithelial interactions and pathogenicity mechanisms: scratching the surface Moyes, David L.; Richardson, Jonathan P.; Naglik, Julian R. Virulence, Vol. 6, Issue 4 https://doi.org/10.1080/21505594.2015.1012981	journal	January 2015
Vesicle-associated melanization in Cryptococcus neoformans Eisenman, Helene C.; Frases, Susana; Nicola, André M. Microbiology, Vol. 155, Issue 12 https://doi.org/10.1099/mic.0.032854-0	journal	December 2009
From Attachment to Damage: Defined Genes of Candida albicans Mediate Adhesion, Invasion and Damage during Interaction with Oral Epithelial Cells Wächtler, Betty; Wilson, Duncan; Haedicke, Katja PLoS ONE, Vol. 6, Issue 2 https://doi.org/10.1371/journal.pone.0017046	journal	February 2011
Extracellular Vesicles from Aspergillus flavus Induce M1 Polarization In Vitro Brauer, Verônica S.; Pessoni, André M.; Bitencourt, Tamires A. mSphere, Vol. 5, Issue 3 https://doi.org/10.1128/mSphere.00190-20	journal	June 2020
Systematic screens of a Candida albicans homozygous deletion library decouple morphogenetic switching and pathogenicity Noble, Suzanne M.; French, Sarah; Kohn, Lisa A. Nature Genetics, Vol. 42, Issue 7 https://doi.org/10.1038/ng.605	journal	June 2010
Extracellular Vesicles From Sporothrix brasiliensis Are an Important Virulence Factor That Induce an Increase in Fungal Burden in Experimental Sporotrichosis Ikeda, Marcelo Augusto Kazuo; de Almeida, José Roberto Fogaça; Jannuzzi, Grasielle Pereira Frontiers in Microbiology, Vol. 9 https://doi.org/10.3389/fmicb.2018.02286	journal	October 2018
Proteomics Unravels Extracellular Vesicles as Carriers of Classical Cytoplasmic Proteins in Candida albicans Gil-Bona, Ana; Llama-Palacios, Arancha; Parra, Claudia Marcela Journal of Proteome Research, Vol. 14, Issue 1 https://doi.org/10.1021/pr5007944	journal	October 2014
Characteristics of Extracellular Vesicles Released by the Pathogenic Yeast-Like Fungi Candida glabrata, Candida parapsilosis and Candida tropicalis Karkowska-Kuleta, Justyna; Kulig, Kamila; Karnas, Elzbieta Cells, Vol. 9, Issue 7 https://doi.org/10.3390/cells9071722	journal	July 2020
Extracellular nanovesicles released from the commensal yeast Malassezia sympodialis are enriched in allergens and interact with cells in human skin Johansson, Henrik J.; Vallhov, Helen; Holm, Tina Scientific Reports, Vol. 8, Issue 1 https://doi.org/10.1038/s41598-018-27451-9	journal	June 2018
Multi-omics Signature of Candida auris , an Emerging and Multidrug-Resistant Pathogen Zamith-Miranda, Daniel; Heyman, Heino M.; Cleare, Levi G. mSystems, Vol. 4, Issue 4 https://doi.org/10.1128/mSystems.00257-19	journal	June 2019
Cryptococcus neoformans Glucuronoxylomannan and Sterylglucoside Are Required for Host Protection in an Animal Vaccination Model Colombo, Ana Caroline; Rella, Antonella; Normile, Tyler mBio, Vol. 10, Issue 2 https://doi.org/10.1128/mBio.02909-18	journal	April 2019
Glucosylceramides From Lomentospora prolificans Induce a Differential Production of Cytokines and Increases the Microbicidal Activity of Macrophages Xisto, Mariana Ingrid Dutra da Silva; Henao, Julián Esteban Muñoz; Dias, Lucas dos Santos Frontiers in Microbiology, Vol. 10 https://doi.org/10.3389/fmicb.2019.00554	journal	March 2019
Here, There, and Everywhere: The Ubiquitous Distribution of the Immunosignaling Molecule Lysophosphatidylcholine and Its Role on Chagas Disease Silva-Neto, Mário Alberto C.; Lopes, Angela H.; Atella, Georgia C. Frontiers in Immunology, Vol. 7 https://doi.org/10.3389/fimmu.2016.00062	journal	February 2016
Migration to Apoptotic “Find-me” Signals Is Mediated via the Phagocyte Receptor G2A Peter, Christoph; Waibel, Michaela; Radu, Caius G. Journal of Biological Chemistry, Vol. 283, Issue 9 https://doi.org/10.1074/jbc.M706586200	journal	December 2007
RNA-Seq analysis in MeV Howe, E. A.; Sinha, R.; Schlauch, D. Bioinformatics, Vol. 27, Issue 22 https://doi.org/10.1093/bioinformatics/btr490	journal	October 2011
Combination Therapy of Chloroquine and C2-Ceramide Enhances Cytotoxicity in Lung Cancer H460 and H1299 Cells Chou, Han-Lin; Lin, Yi-Hsiung; Liu, Wangta Cancers, Vol. 11, Issue 3 https://doi.org/10.3390/cancers11030370	journal	March 2019
Changes in glucosylceramide structure affect virulence and membrane biophysical properties of Cryptococcus neoformans Raj, Shriya; Nazemidashtarjandi, Saeed; Kim, Jihyun Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1859, Issue 11 https://doi.org/10.1016/j.bbamem.2017.08.017	journal	November 2017
Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists Huang, Da Wei; Sherman, Brad T.; Lempicki, Richard A. Nucleic Acids Research, Vol. 37, Issue 1 https://doi.org/10.1093/nar/gkn923	journal	November 2008
High glucose-mediated overexpression of ICAM-1 in human vaginal epithelial cells increases adhesion of Candida albicans Mikamo, Hiroshige; Yamagishi, Yuka; Sugiyama, Hiroyuki Journal of Obstetrics and Gynaecology, Vol. 38, Issue 2 https://doi.org/10.1080/01443615.2017.1343810	journal	September 2017
Concentration-dependent protein loading of extracellular vesicles released by Histoplasma capsulatum after antibody treatment and its modulatory action upon macrophages Baltazar, Ludmila Matos; Zamith-Miranda, Daniel; Burnet, Meagan C. Scientific Reports, Vol. 8, Issue 1 https://doi.org/10.1038/s41598-018-25665-5	journal	May 2018
Selective Export into Extracellular Vesicles and Function of tRNA Fragments during T Cell Activation Chiou, Ni-Ting; Kageyama, Robin; Ansel, K. Mark Cell Reports, Vol. 25, Issue 12 https://doi.org/10.1016/j.celrep.2018.11.073	journal	December 2018
Extracellular vesicle-mediated export of fungal RNA Peres da Silva, Roberta; Puccia, Rosana; Rodrigues, Marcio L. Scientific Reports, Vol. 5, Issue 1 https://doi.org/10.1038/srep07763	journal	January 2015
Extracellular Vesicles From the Dermatophyte Trichophyton interdigitale Modulate Macrophage and Keratinocyte Functions Bitencourt, Tamires Aparecida; Rezende, Caroline Patini; Quaresemin, Natália Renault Frontiers in Immunology, Vol. 9 https://doi.org/10.3389/fimmu.2018.02343	journal	October 2018
Vesicle and Vesicle-Free Extracellular Proteome of Paracoccidioides brasiliensis : Comparative Analysis with Other Pathogenic Fungi Vallejo, Milene C.; Nakayasu, Ernesto S.; Matsuo, Alisson L. Journal of Proteome Research, Vol. 11, Issue 3 https://doi.org/10.1021/pr200872s	journal	January 2012
Characterization of Aspergillus fumigatus Extracellular Vesicles and Their Effects on Macrophages and Neutrophils Functions Souza, Jéssica Amanda Marques; Baltazar, Ludmila de Matos; Carregal, Virgínia Mendes Frontiers in Microbiology, Vol. 10 https://doi.org/10.3389/fmicb.2019.02008	journal	September 2019
Extracellular vesicles secreted by Saccharomyces cerevisiae are involved in cell wall remodelling Zhao, Kening; Bleackley, Mark; Chisanga, David Communications Biology, Vol. 2, Issue 1 https://doi.org/10.1038/s42003-019-0538-8	journal	August 2019
Ant venoms Hoffman, Donald R. Current Opinion in Allergy & Clinical Immunology, Vol. 10, Issue 4 https://doi.org/10.1097/ACI.0b013e328339f325	journal	January 2010

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Title: Comparative Molecular and Immunoregulatory Analysis of Extracellular Vesicles from Candida albicans and Candida auris

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