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Cited by 123Antifungal resistance and susceptibilityFungal and yeast genetics researchExtracellular vesicles in disease

Coordination of fungal biofilm development by extracellular vesicle cargo

Open access
Zarnowski, Robert, Noll, Andrea, Chevrette, Marc G., Sanchez, Hiram, Jones, Ryley, Anhalt, Hanna, Fossen, Jen, Jaromin, Anna +4 more·2021·Nature Communications
DOI 10.1038/s41467-021-26525-zPMC PMC8556236
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Abstract

The fungal pathogen Candida albicans can form biofilms that protect it from drugs and the immune system. The biofilm cells release extracellular vesicles (EVs) that promote extracellular matrix formation and resistance to antifungal drugs. Here, we define functions for numerous EV cargo proteins in biofilm matrix assembly and drug resistance, as well as in fungal cell adhesion and dissemination. We use a machine-learning analysis of cargo proteomic data from mutants with EV production defects to identify 63 candidate gene products for which we construct mutant and complemented strains for study. Among these, 17 mutants display reduced biofilm matrix accumulation and antifungal drug resistance. An additional subset of 8 cargo mutants exhibit defects in adhesion and/or dispersion. Representative cargo proteins are shown to function as EV cargo through the ability of exogenous wild-type EVs to complement mutant phenotypic defects. Most functionally assigned cargo proteins have roles in two or more of the biofilm phases. Our results support that EVs provide community coordination throughout biofilm development in C. albicans .

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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 [27]

    The Results section (‘ESCRT pathway directs vesicle cargo composition’; page unavailable) says C. albicans biofilm EVs deliver an adhesive extracellular matrix. The cited paper does not establish that several Candida species deliver a specifically mannan-glucan complex via EVs; its experiments focus on C. albicans. (LLM, conf=0.86)

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Sorted by citations

Authors
Zarnowski, R., Noll, A., Chevrette, M. G., Sanchez, H., Jones, R., Anhalt, H., Fossen, J., Jaromin, A., Currie, C., Nett, J. E., Mitchell, A., & Andes, D. R.
Affiliations
  • University of Wisconsin–Madison (US)
  • University of Wrocław (PL)
  • University of Georgia (US)
Corresponding author
  • Mitchell, Aaron
  • Andes, David R.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2021-10-29
Volume
12
Issue
1
Pages
6235-6235
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-021-26525-z
PMC
PMC8556236
OpenAlex
W3210677157
Cited by
123
References
7
Citations by year
2026: 21 · 2025: 34 · 2024: 30 · 2023: 23 · 2022: 15
FWCI
5.46
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
U.S. Department of Health & Human Services | 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
Candida albicans, fungal biofilms, extracellular vesicles, antifungal resistance, fungal dispersal, community coordination, complementation
MeSH terms
Extracellular Vesicles, Animals, Antifungal Agents, Candida albicans, Candidiasis, Cell Adhesion, Extracellular Matrix, Female, Fungal Proteins, Mutation, Biofilms, Drug Resistance, Fungal, Rats, Endosomal Sorting Complexes Required for Transport, Central Venous Catheters

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