Dataset Information

Vesicle proteomics during fungal biofilm development in Candida

ABSTRACT: Proteomic profiling of extracellular vesicles from four different Candida strains (tropicalis, parapsilosis, auris and glabrata).

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): [candida] Auris Candida Tropicalis (yeast) Candida Glabrata (yeast) (torulopsis Glabrata) Candida Parapsilosis

TISSUE(S): Extracellular Vesicle, Biofilm

SUBMITTER: Greg Sabat

LAB HEAD: Dr. David Andes

PROVIDER: PXD035068 | Pride | 2022-10-14

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	10_CG_48hrs__F018961_.mzid.gz	Mzid
	10_CG_48hrs__F018961_.mzid_10_CG_48hrs__F018961_.MGF	Mzid
	48hrB-Vesicles__F019623_.mzid.gz	Mzid
	48hrB-Vesicles__F019623_.mzid_48hrB-Vesicles__F019623_.MGF	Mzid
	6_CT_48hrs__F018948_.mzid.gz	Mzid

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Publications

A common vesicle proteome drives fungal biofilm development.

Zarnowski Robert R Sanchez Hiram H Jaromin Anna A Zarnowska Urszula J UJ Nett Jeniel E JE Mitchell Aaron P AP Andes David D

Proceedings of the National Academy of Sciences of the United States of America 20220912 38

Extracellular vesicles mediate community interactions among cells ranging from unicellular microbes to complex vertebrates. Extracellular vesicles of the fungal pathogen Candida albicans are vital for biofilm communities to produce matrix, which confers environmental protection and modulates community dispersion. Infections are increasingly due to diverse Candida species, such as the emerging pathogen Candida auris, as well as mixed Candida communities. Here, we defin ...[more]

PMID: 36095193

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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.