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Updated: Aug 29, 2025
In Vesiculo Synthesis of Peptide Membrane Precursors for Autonomous Vesicle Growth
Published on: June 28, 2019
A common vesicle proteome drives fungal biofilm development
Robert Zarnowski1,2, Hiram Sanchez1,2, Anna Jaromin3
1Department of Medicine, University of Wisconsin, Madison, WI.
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.
Insights
Fungal extracellular vesicles mediate community interactions and biofilm development in Candida species. These vesicles, containing common proteins, influence drug tolerance and dispersion, impacting both single-species and mixed-species infections.
Area of Science:
- Microbiology
- Cell Biology
- Mycology
Background:
- Extracellular vesicles (EVs) are crucial for intercellular communication in various organisms.
- In the fungal pathogen Candida albicans, EVs are essential for biofilm matrix production, environmental protection, and community dispersion.
- Increasing infections involve diverse Candida species and mixed Candida communities, highlighting the need to understand interspecies interactions.
Purpose of the Study:
- To characterize the composition and function of biofilm-associated EVs across five Candida species.
- To investigate the role of common EV cargo proteins in key biofilm processes like drug tolerance and dispersion.
- To assess the impact of EVs on interspecies interactions within mixed Candida communities.
Main Methods:
- Comparative proteomic analysis of EVs from five Candida species.
- Construction and phenotypic analysis of mutants lacking key EV cargo proteins.
- Functional assays for biofilm formation, matrix production, drug tolerance, and dispersion.
- Cross-species EV addition experiments and mixed-species biofilm studies.
Main Results:
- Candida EVs exhibit conserved size and release patterns but distinct cargo proteomes across species.
- A core set of 36 common EV proteins, enriched for biofilm mediators, significantly impacts drug tolerance and dispersion in all tested species.
- Exogenous delivery of wild-type EV cargo restored mutant phenotypes.
- Cross-species EV addition demonstrated functional complementation, restoring wild-type biofilm behavior in mixed-species communities.
Conclusions:
- Candida EVs play a significant role in shaping both monomicrobial and polymicrobial biofilm communities.
- EVs facilitate interspecies communication and cooperation, influencing community-level drug resistance and development.
- Understanding EV-mediated interactions is critical for combating diverse and mixed Candida infections.
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