Candida albicans Hyphal Extracellular Vesicles Are Different from Yeast Ones, Carrying an Active Proteasome Complex and Showing a Different Role in Host Immune Response.
Date
2022-06-29ICR Author
Author
Martínez-López, R
Hernáez, ML
Redondo, E
Calvo, G
Radau, S
Pardo, M
Gil, C
Monteoliva, L
Vylkova S
Type
Journal Article
Metadata
Show full item recordAbstract
Candida albicans is the principal causative agent of lethal fungal infections, predominantly in immunocompromised hosts. Extracellular vesicles (EVs) have been described as crucial in the interaction of microorganisms with their host. Since the yeast-to-hypha transition is an important virulence trait with great impact in invasive candidiasis (IC), we have addressed the characterization of EVs secreted by hyphal cells (HEVs) from C. albicans, comparing them to yeast EVs (YEVs). YEVs comprised a larger population of bigger EVs with mainly cell wall proteins, while HEVs were smaller, in general, and had a much higher protein diversity. YEVs were able to rescue the sensitivity of a cell wall mutant against calcofluor white, presumably due to the larger amount of cell wall proteins they contained. On the other hand, HEVs also contained many cytoplasmic proteins related to protein metabolism and intracellular protein transport and the endosomal sorting complexes required for transport (ESCRT) pathway related to exosome biogenesis, pointing to an intracellular origin of HEVs. Interestingly, an active 20S proteasome complex was secreted exclusively in HEVs. Moreover, HEVs contained a greater number of virulence-related proteins. As for their immunogenic role, both types of EV presented immune reactivity with human sera from patients suffering invasive candidiasis; however, under our conditions, only HEVs showed a cytotoxic effect on human macrophages and could elicit the release of tumor necrosis factor alpha (TNF-α) by these macrophages. IMPORTANCE This first analysis of HEVs of C. albicans has shown clear differences between them and the YEVs of C. albicans, showing their relevance and possible use in the discovery of new diagnostic markers and treatment targets against C. albicans infections. The data obtained point to different mechanisms of biogenesis of YEVs and HEVs, as well as different involvements in cell biology and host interaction. YEVs played a more relevant role in cell wall maintenance, while HEVs were more closely related to virulence, as they had greater effects on human immune cells. Importantly, an active 20S proteosome complex was described as a fungal-EV cargo. A deeper study of its role and those of many other proteins exclusively detected in HEVs and involved in different relevant biological processes of this fungus could open up interesting new areas of research in the battle against C. albicans.
Collections
Subject
Candida albicans
cell wall maintenance
exosomes
extracellular vesicles
hyphae
immunogenic
macrophages
proteasome
proteomics
virulence factors
yeast
Candida albicans
Candidiasis
Candidiasis, Invasive
Extracellular Vesicles
Fungal Proteins
Humans
Hyphae
Immunity
Proteasome Endopeptidase Complex
Tumor Necrosis Factor-alpha
Research team
Functional Proteomics
Language
eng
Date accepted
2022-04-13
License start date
2022-06-29
Citation
Microbiology Spectrum, 2022, 10 (3), pp. e0069822 -
Publisher
AMER SOC MICROBIOLOGY