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.
Highlights
Glucans, chitin, and glycoproteins are cross-linked to form the most essential structure of fungal cell walls (Free, 2013)
Major hits include enzymes required for glycolysis, fermentation, gluconeogenesis, pentose phosphate, tricarboxylic acid, and glyoxylate cycles (Table 1) (Albuquerque et al, 2008; Rodrigues et al, 2008; Vallejo et al, 2011; Vargas et al, 2015). In this group of molecules, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), enolase, and transaldolase were consistently detected in C. neoformans, C. albicans, P. brasiliensis, and Histoplasma capsulatum extracellular vesicles (EVs) by proteomic analysis (Rodrigues et al, 2008; Vallejo et al, 2011; Wolf et al, 2014; Gil-Bona et al, 2015a; Vargas et al, 2015)
In addition Cn-rHSP70 can upregulate TLR4 expression in macrophages (Silveira et al, 2013) and directly interfere with early macrophage polarization, limiting innate control of C. neoformans (Eastman et al, 2015). These results indicate that EVs carry proteins that facilitate C. neoformans survival within the host
Summary
Chitin, and glycoproteins are cross-linked to form the most essential structure of fungal cell walls (Free, 2013). EVs from Cryptoccocus neoformans and Candida albicans are recognized and internalized by phagocytes culminating in host cell activation (Oliveira et al, 2010; Vargas et al, 2015).
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