Journal Article

Candida albicans biofilm–induced vesicles confer drug resistance through matrix biogenesis

Jaromin, Anna, Sanchez, Hiram, Mitchell, Aaron, Bernhardt, Jörg, Zarnowski, Robert, Covelli, Antonio S., Dominguez, Eddie, Mitchell, Kaitlin F., Azadi, Parastoo, Heiss, Christian, Andes, David R.

2018

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Antimicrobial agents / BASIC BIOLOGICAL SCIENCES / biochemistry & molecular biology / Biofilms / Biofilms - drug effects / Biofilms - growth & development / Biology and Life Sciences / Biosynthesis / Candida albicans / Candida albicans - drug effects / Candida albicans - pathogenicity / Candida albicans - physiology / Cell interactions / Chemical communication / Communities / Cryoelectron Microscopy / Diabetes / Drug resistance / Drug Resistance, Fungal / Endosomal Sorting Complexes Required for Transport - genetics / Endosomal Sorting Complexes Required for Transport - physiology / Eukaryotes / Evolution / Extracellular matrix / Extracellular Polymeric Substance Matrix - drug effects / Extracellular Polymeric Substance Matrix - physiology / Extracellular Polymeric Substance Matrix - ultrastructure / Extracellular Vesicles - drug effects / Extracellular Vesicles - physiology / Extracellular Vesicles - ultrastructure / Flow cytometry / Fluconazole / Fourier transforms / Fungal Proteins - metabolism / Fungicides / Gene expression / Humans / Hypersensitivity / Immunology / Infectious diseases / life sciences & biomedicine / Lipid bilayers / Lipid Metabolism / Lipids / Mass spectrometry / Medical equipment / Medicine / Medicine and Health Sciences / Microbial Interactions - drug effects / Microbial Interactions - physiology / Microorganisms / Microscopy, Electron, Scanning / Models, Biological / Mutants / Mutation / Planktonic cells / Polysaccharides / Proteins / Proteome - metabolism / Quorum sensing / Relaying / Research and Analysis Methods / Scientific imaging / Short Reports / Vesicles