Biological Roles Played by Sphingolipids in Dimorphic and Filamentous Fungi

Abstract

Filamentous and dimorphic fungi cause invasive mycoses associated with high mortality rates. Among the fungal determinants involved in the establishment of infection, glycosphingolipids (GSLs) have gained increased interest in the last few decades. GSLs are ubiquitous membrane components that have been isolated from both filamentous and dimorphic species and play a crucial role in polarized growth as well as hypha-to-yeast transition. In fungi, two major classes of GSLs are found: neutral and acidic GSLs. Neutral GSLs comprise glucosylceramide and galactosylceramide, which utilize Δ4-Δ8-9-methyl-sphingadienine as a sphingoid base, linked to a C16–18 fatty acid chain, forming ceramide, and to a sugar residue, such as glucose or galactose. In contrast, acidic GSLs include glycosylinositol phosphorylceramides (GIPCs), composed of phytosphingosine attached to a long or very long fatty acid chain (C18–26) and to diverse and complex glycan groups via an inositol-phosphate linker. GIPCs are absent in mammalian cells, while fungal glucosylceramide and galactosylceramide are present but diverge structurally from their counterparts. Therefore, these compounds and their biosynthetic pathways represent potential targets for the development of selective therapeutic strategies. In this minireview, we discuss the enzymatic steps involved in the production of fungal GSLs, analyze their structure, and address the role of the currently characterized genes in the biology and pathogenesis of filamentous and dimorphic fungi.

The Regulatory Proteins Rtg1/3 Govern Sphingolipid Homeostasis in the Human-Associated Yeast Candida albicans

“…Their involvement in a broad range of functions arises from the wide variation in carbon chain length, degree and location of unsaturation and hydroxylation, as well as other modifications (e.g., glycosylation) that these molecules undergo (Huang et al, 2012). Glycosphingolipids are also important determinants of cellular growth, morphological transitions, and virulence in various human fungal pathogens (Fernandes et al, 2018;Heung et al, 2006). The first steps in the biosynthesis of sphingolipids are highly conserved from yeasts to metazoans, whereas fungi produce a series of complex glycosphingolipids-e.g., inositol phosphoceramides (IPCs), mannosyl-inositolphosphorylceramide (MIPC), and mannosyl-diinositolphosphorylceramide [M(IP) 2 C]-that are not made by mammals.…”

“…The first steps in the biosynthesis of sphingolipids are highly conserved from yeasts to metazoans, whereas fungi produce a series of complex glycosphingolipids-e.g., inositol phosphoceramides (IPCs), mannosyl-inositolphosphorylceramide (MIPC), and mannosyl-diinositolphosphorylceramide [M(IP) 2 C]-that are not made by mammals. Accordingly, targeting the synthesis of fungal-specific glycosphingolipids has been proposed as a strategy for the development of novel antifungal drugs (Fernandes et al, 2018). The mechanisms that maintain sphingolipid homeostasis in these organisms, however, remain largely unexplored.…”

In vitro resynthesis of lichenization reveals the genetic background of symbiosis-specific fungal-algal interaction in Usnea hakonensis.

“…Expression of genes involved in sphingolipid and phospholipid biosynthesis were up-regulated in the symbiotic states (Uhk_003277, Uhk_017380, and Uhk_017885). Sphingolipids and phospholipids are constitutive lipids of membrane microdomains and extracellular vesicles respectively (29,30,67,68), both reported to be involved in the communication between symbiotic partners (69)(70)(71)(72)(73). The up-regulated expression of the genes involved in these fungal lipid metabolisms might suggest that lipids are not merely the components of the hydrophobic layer but also used as fungal tools to communicate with algal partners (Figure 2e).…”

Genome-wide Identification of the Aspergillus oryzae GATA Transcription Factor Gene Family and expression Analysis under Temperature or Salt Stresses

“…The temperature and salt concentration are two of the most important environmental factors affecting the growth of A. oryzae during fermentation process [21,22,23,24,25]. Therefore, we investigated the growth of A. oryzae under different temperature and salt concentration stresses.…”

“…Simultaneously, A. oryzae is exposed to environmental stress factors during fermentation process. For example, temperature is the most important environmental factor affecting the growth and activity of microorganisms and can directly affect the activity of enzymes involved in substrate digestion during fermentation process [22,23]. In addition, high sodium chloride concentrations are added to soy sauce mash to inhibit the growth of spoilage bacteria during fermentation process, but high salt concentrations also inhibit the growth of A. oryzae [24,25].…”