Cited by 63Antifungal resistance and susceptibilityFungal and yeast genetics researchExtracellular vesicles in disease

A common vesicle proteome drives fungal biofilm development

Open access
Zarnowski, Robert, Sanchez, Hiram, Jaromin, Anna, Zarnowska, Urszula J., Nett, Jeniel E., Mitchell, Aaron P., Andes, David·2022·Proceedings of the National Academy of Sciences

Abstract

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 define the composition and function of biofilm-associated vesicles among five species across the Candida genus. We find similarities in vesicle size and release over the biofilm lifespan. Whereas overall cargo proteomes differ dramatically among species, a group of 36 common proteins is enriched for orthologs of C. albicans biofilm mediators. To understand the function of this set of proteins, we asked whether mutants in select components were important for key biofilm processes, including drug tolerance and dispersion. We found that the majority of these cargo components impact one or both biofilm processes across all five species. Exogenous delivery of wild-type vesicle cargo returned mutant phenotypes toward wild type. To assess the impact of vesicle cargo on interspecies interactions, we performed cross-species vesicle addition and observed functional complementation for both biofilm phenotypes. We explored the biologic relevance of this cross-species biofilm interaction in mixed species and mutant studies examining the drug-resistance phenotype. We found a majority of biofilm interactions among species restored the community’s wild-type behavior. Our studies indicate that vesicles influence the development of protective monomicrobial and mixed microbial biofilm communities.

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Crossref · 10.1073/pnas.2211424119

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  • Several Candida species produce a unique biofilm extracellular matrix mannan-glucan complex that is delivered via EVs.

    “Several Candida species produce a unique biofilm extracellular matrix mannan-glucan complex that is delivered via EVs (25–28).”

    From Dual function of <i>Candida auris</i> mannosyltransferase, MNT5, in biofilm community protection from antifungal therapy and the host (2025) · cites this paper as [25]

    The Results (Comparison of Vesicle Cargo Composition; page unavailable) report that several Candida species produce biofilm vesicles containing mannan and glucan in ratios compatible with assembly of the matrix mannan–glucan complex. The paper says this suggests EV delivery of the complex’s building blocks; it does not establish that the assembled complex itself is delivered via EVs. (LLM, conf=0.86)

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Research works printed but not linked: 2

  1. [65]R. Mancuso, Functions of Candida albicans cell wall glycosidases Dfg5p and Dcw1p in biofilm formation and HOG MAPK pathway. PeerJ 6, e5685 (2018). 30280048 PMC6166624
  2. [89]D. N. Perkins, D. J. Pappin, D. M. Creasy, J. S. Cottrell, Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis 20, 3551– 3567 (1999). 10612281

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Authors
Zarnowski, R., Sanchez, H., Jaromin, A., Zarnowska, U. J., Nett, J. E., Mitchell, A. P., & Andes, D.
Affiliations
  • Department of Medicine, University of Wisconsin, Madison, WI
  • University of Wrocław (PL)
  • University of Wisconsin–Madison (US)
  • University of Georgia (US)
Corresponding author
  • Mitchell, Aaron P.
  • Andes, David
Venue
Proceedings of the National Academy of Sciences
Published
2022-09-12
Volume
119
Issue
38
Pages
e2211424119-e2211424119
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W4295309184
Cited by
63
References
98
Citations by year
2026: 13 · 2025: 18 · 2024: 18 · 2023: 12 · 2022: 2
FWCI
6.23
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
HHS | NIH | National Institute of Allergy and Infectious Diseases (R01AI073289)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Keywords
extracellular vesicles, fungal biofilms, Candida, Candida albicans, Candida auris, orthologs, drug tolerance, biofilm dispersal, interspecies interactions, mixed microbial communities, functional complementation, fungal pathogenesis
MeSH terms
Extracellular Vesicles, Animals, Candida albicans, Fungal Proteins, Biofilms, Proteome, Drug Resistance, Fungal

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