Coordination of fungal biofilm development by extracellular vesicle cargo.
Robert ZarnowskiAndrea NollMarc G ChevretteHiram SanchezRyley JonesHanna AnhaltJen FossenAnna JarominCameron R CurrieJeniel E NettAaron P MitchellDavid R AndesPublished in: Nature communications (2021)
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.
Keyphrases
- candida albicans
- wild type
- biofilm formation
- extracellular matrix
- machine learning
- cell adhesion
- healthcare
- escherichia coli
- gene expression
- staphylococcus aureus
- big data
- genome wide
- induced apoptosis
- oxidative stress
- cystic fibrosis
- electronic health record
- cell death
- dna methylation
- artificial intelligence
- cell cycle arrest
- data analysis
- signaling pathway
- pi k akt