Extracellular Vesicle-Associated Transitory Cell Wall Components and Their Impact on the Interaction of Fungi with Host Cells

Abstract

Classic cell wall components of fungi comprise the polysaccharides glucans and chitin, in association with glycoproteins and pigments. During the last decade, however, system biology approaches clearly demonstrated that the composition of fungal cell walls include atypical molecules historically associated with intracellular or membrane locations. Elucidation of mechanisms by which many fungal molecules are exported to the extracellular space suggested that these atypical components are transitorily located to the cell wall. The presence of extracellular vesicles (EVs) at the fungal cell wall and in culture supernatants of distinct pathogenic species suggested a highly functional mechanism of molecular export in these organisms. Thus, the passage of EVs through fungal cell walls suggests remarkable molecular diversity and, consequently, a potentially variable influence on the host antifungal response. On the basis of information derived from the proteomic characterization of fungal EVs from the yeasts Cryptoccocus neoformans and Candida albicans and the dimorphic fungi Histoplasma capsulatum and Paracoccidioides brasiliensis, our manuscript is focused on the clear view that the fungal cell wall is much more complex than previously thought.

Keywords: cell wall remodeling; extracellular vesicles; fungal cell wall; host cell; proteomics.

FIGURE 1

Schematic illustration of a fungal cell wall and its major polysaccharides and proteins (based on species with protein EV composition characterized). Extracellular vesicles (EVs) are shown as bilayered compartments. Structural polysaccharides include chitin (green, close to plasma membrane), β1,3 (blue), and β1,6 glucans (yellow). Chitin oligomers (green, distributed across the cell wall), mannans, and mannoproteins (solid and fuzzy red) are also illustrated. EVs traverse the cell wall potentially promoting remodeling through hydrolysis of polysaccharides and mannoproteins and exposing internal structural components to the extracellular environment. For didactic purposes, melanin, lipids, capsule, β 1,4, and α 1,4 glucans and other cell wall components are not illustrated in this model.