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Updated: Feb 4, 2026
Candida albicans Biofilm Chip CaBChip for High-throughput Antifungal Drug Screening
Published on: July 18, 2012
Candida albicans biofilm-induced vesicles confer drug resistance through matrix biogenesis
Robert Zarnowski1,2, Hiram Sanchez1,2, Antonio S Covelli1,2
1Department of Medicine, Section of Infectious Diseases, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Abstract:
Cells from all kingdoms of life produce extracellular vesicles (EVs). Their cargo is protected from the environment by the surrounding lipid bilayer. EVs from many organisms have been shown to function in cell-cell communication, relaying signals that impact metazoan development, microbial quorum sensing, and pathogenic host-microbe interactions. Here, we have investigated the production and functional activities of EVs in a surface-associated microbial community or biofilm of the fungal pathogen Candida albicans. Crowded communities like biofilms are a context in which EVs are likely to function. Biofilms are noteworthy because they are encased in an extracellular polymeric matrix and because biofilm cells exhibit extreme tolerance to antimicrobial compounds. We found that biofilm EVs are distinct from those produced by free-living planktonic cells and display strong parallels in composition to biofilm matrix material. The functions of biofilm EVs were delineated with a panel of mutants defective in orthologs of endosomal sorting complexes required for transport (ESCRT) subunits, which are required for normal EV production in diverse eukaryotes. Most ESCRT-defective mutations caused reduced biofilm EV production, reduced matrix polysaccharide levels, and greatly increased sensitivity to the antifungal drug fluconazole. Matrix accumulation and drug hypersensitivity of ESCRT mutants were reversed by addition of wild-type (WT) biofilm EVs. Vesicle complementation showed that biofilm EV function derives from specific cargo proteins. Our studies indicate that C. albicans biofilm EVs have a pivotal role in matrix production and biofilm drug resistance. Biofilm matrix synthesis is a community enterprise; prior studies of mixed cell biofilms have demonstrated extracellular complementation. Therefore, EVs function not only in cell-cell communication but also in the sharing of microbial community resources.
Insights
Extracellular vesicles (EVs) from Candida albicans biofilms are crucial for matrix production and drug resistance. These microbial community resources, distinct from planktonic EVs, are essential for biofilm integrity and antifungal tolerance.
Area of Science:
- Microbiology
- Mycology
- Cell Biology
Background:
- Extracellular vesicles (EVs) are produced by cells across all kingdoms of life and mediate intercellular communication.
- Biofilms, surface-associated microbial communities, are characterized by an extracellular polymeric matrix and enhanced tolerance to antimicrobials.
- Candida albicans is a significant fungal pathogen that forms biofilms, posing challenges in clinical settings.
Purpose of the Study:
- To investigate the production and functional roles of EVs in Candida albicans biofilms.
- To determine if biofilm EVs differ in composition and function from those produced by planktonic cells.
- To elucidate the involvement of EVs in biofilm matrix production and antifungal drug resistance.
Main Methods:
- Comparative analysis of EVs from biofilm and planktonic Candida albicans cells.
- Utilized mutants defective in endosomal sorting complexes required for transport (ESCRT) subunits to assess EV production and function.
- Complemented ESCRT mutants with wild-type biofilm EVs to evaluate rescue of biofilm matrix and drug resistance phenotypes.
- Analyzed EV cargo proteins to identify functional components.
Main Results:
- Biofilm EVs exhibit distinct compositions, paralleling biofilm matrix material, and differ from planktonic EVs.
- ESCRT-defective mutants showed reduced biofilm EV production, decreased matrix polysaccharide levels, and increased susceptibility to fluconazole.
- Addition of wild-type biofilm EVs restored matrix accumulation and reversed drug hypersensitivity in ESCRT mutants.
- Vesicle complementation confirmed that specific cargo proteins within biofilm EVs mediate their functions.
Conclusions:
- Candida albicans biofilm EVs play a pivotal role in biofilm matrix production and contribute significantly to antifungal drug resistance.
- EVs facilitate the sharing of community resources within the biofilm, extending beyond cell-cell communication.
- Targeting biofilm EVs could represent a novel strategy to combat Candida albicans infections.
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