Abstract
ABSTRACTFilamentous 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.
Highlights
Filamentous and dimorphic fungi cause invasive mycoses associated with high mortality rates
GlcCer has been isolated from several fungal species, the role of the glucosylceramide synthase (GCS) in polarized growth has been investigated only in the filamentous A. fumigatus, A. nidulans, and F. graminearum
Previous observations in clinical isolates of Candida glabrata demonstrated that caspofungin reduced susceptibility (CRS)-micafungin increased susceptibility (MIS) is associated with higher levels of DhSph and PhSph [71]. These results suggest that the CRS-MIS phenotype observed in the A. nidulans basA1 strain can be attributed to the accumulation of DhSph and indicate that sphingolipids may interact with echinocandins or/and with Fks
Summary
Filamentous and dimorphic fungi cause invasive mycoses associated with high mortality rates. Whereas the role of the host immune system in fungal recognition and growth inhibition and, in controlling the infection has been extensively studied [12, 14], the pathways that contribute to fungal virulence, those involved in the regulation of hypha-to-yeast transition and conidial germination in dimorphic and filamentous fungi, are less appreciated.
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