Dataset Information

Candida albicans biofilm extracellular vesicles deliver candidalysin to epithelial cell membranes and induce host cell responses

ABSTRACT: Extracellular vesicles (EVs) are heterogeneous particles encapsulated with a phospholipid bilayer membrane. EVs have evolved diverse biological functions, serving mainly as prominent mediators and regulators of cell-cell communication. Fungal EVs contain numerous factors involved in a diverse array of biological functions including biogenesis of extracellular matrix proteins and saccharides, antifungal resistance, and pathogenesis. This study investigated whether candidalysin, a peptide toxin that drives C. albicans infections, is present in EVs derived from C. albicans biofilms. We found that those EVs contain candidalysin at low levels and can permeabilize planar lipid bilayers membranes in a dose-dependent manner but are unable to damage oral epithelial cells (OECs). Application of EVs to OECs induced cytokine responses but did not activate MAPK signalling. Notably, EVs obtained from biofilms cultured for 24 h and 48 h exhibited differences in cargo composition and their ability to activate OECs. This study suggests that secreted EVs can serve as a toxin delivery system during C. albicans infection but also possess different functions depending on their maturity.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Candida Albicans Sc5314

TISSUE(S): Cell Suspension Culture, Extracellular Exosome

SUBMITTER: Greg Sabat

LAB HEAD: David Andes

PROVIDER: PXD045873 | Pride | 2025-05-26

REPOSITORIES: Pride

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Candida albicans biofilm extracellular vesicles deliver candidalysin to epithelial cell membranes and induce host cell responses.

Lee Sejeong S Tsavou Antzela A Zarnowski Robert R Pforte Rita R Allert Stefanie S Krüger Thomas T Kniemeyer Olaf O Brakhage Axel A AA Bui Tam T T TTT Andes David R DR Richardson Jonathan P JP Hube Bernhard B Naglik Julian R JR

Infection and immunity 20250402 5

Extracellular vesicles (EVs) are heterogeneous particles encapsulated with a phospholipid bilayer membrane. EVs have evolved diverse biological functions, serving mainly as prominent mediators and regulators of cell-cell communication. This study investigated whether candidalysin, a key virulence factor in Candida albicans infections, is present within EVs derived from C. albicans biofilms and retains activity by inducing host immune responses. We found that biofilm EVs contain can ...[more]

PMID: 40172491

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Project description:Background: Acute coronary syndromes (ACS) are associated with aberrant gene expression and epigenetic mechanisms. In particular, de novo DNA methylation is typically linked to gene silencing, but its role in heart disease remains not fully understood. Extracellular vesicles (EVs) are active components in cellular communication for their ability to carry a plethora of signalling biomolecules, thus representing a promising new diagnostic/therapeutic approach in cardiovascular diseases (CVDs). Indeed, there is the need of novel biomarkers for ACS prediction and timely detection. Purpose: We hypothesized that specific epigenetic signals can be carried by EVs. In this regard, we isolated and characterized circulating EVs from ACS patients and evaluated their potential role to influence DNA methylation in target cells. Methods: Circulating EVs were recovered, by ultracentrifugation, from plasma samples of 19 ACS patients and 50 healthy subjects (HS). Nanoparticle tracking analysis (NTA) and western blot (WB) were used to confirm the EVs integrity and purity. Peripheral blood mononuclear cells (PBMCs) of volunteer donors were treated with both ACS and HS derived EVs and genomic DNA was extracted to perform epigenome wide analysis through Reduced Representation Bisulfite Sequencing. ShinyGO, PANTHER, and STRING tools were interrogated to perform GO and PPI network analyses. Flow Cytometry, qRT-PCR, and WB analysis were also performed to evaluate and validate both intra-vesicular and intra-cellular signals. Results: Plasma ACS-derived EVs showed a significant up-regulation of DNA methyltransferases (DNMTs) gene expression levels as compared to HS (P<0.001). Specifically, de novo methylation transcripts, as DNMT3A and DNMT3B were significantly increased in plasma ACS-EVs. DNA methylation analysis of PBMCs from volunteer donors treated with HS- and ACS-derived EVs showed that RNF166 and CCND3 genes resulted the most hyper- and hypo-methylated, respectively, after by ACS-EV treatment. In addition, PPI network analysis specifically evidenced the subnetwork with SRC, as a hub gene, connecting it to NOTCH1, FOXO3, CDC42, IKBKG, RXRA, DGKG, known as important genes already involved in the onset of CVDs. Surprising, other novel genes, BAIAP2, SYP, CHL1, and SHB, which were hypomethylated, were found significantly overexpressed in PBMCs (P<0.005), underlying the fundamental modulating properties of EV cargo in atherosclerosis. Conclusions: These findings support the significant role of ACS plasma-derived EVs, inducing de novo DNA methylation signals, and modulating specific signaling pathways in target cells.

			Action	DRS
	24hr_vesicles.MGF	Mgf
	24hr_vesicles.mzid.gz	Mzid
	24hr_vesicles.raw	Raw
	48hr_vesicles.MGF	Mgf
	48hr_vesicles.mzid.gz	Mzid

Dataset Information

Candida albicans biofilm extracellular vesicles deliver candidalysin to epithelial cell membranes and induce host cell responses

Dataset's files

Publications

<i>Candida albicans</i> biofilm extracellular vesicles deliver candidalysin to epithelial cell membranes and induce host cell responses.

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Dataset Information

Candida albicans biofilm extracellular vesicles deliver candidalysin to epithelial cell membranes and induce host cell responses

Dataset's files

Publications

&lt;i&gt;Candida albicans&lt;/i&gt; biofilm extracellular vesicles deliver candidalysin to epithelial cell membranes and induce host cell responses.

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OmicsDI is part of the ELIXIR infrastructure

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<i>Candida albicans</i> biofilm extracellular vesicles deliver candidalysin to epithelial cell membranes and induce host cell responses.