Synthesis and Biological Properties of Fungal Glucosylceramide

Sphingolipids as Targets for Treatment of Fungal Infections

“…These phenomena were also observed in a C. neoformans mutant lacking the sphingolipid methyltransferase 1 (Δsmt1), which produces GlcCer but it is not methylated [62,63]. This suggests that a specific fungal structure of GlcCer involved in the regulation of specific fungal lipid domains is responsible for the regulation of these phenotypes.…”

“…In dimorphic fungi, such as Histoplasma capsulatum, Paracoccidioides brasiliensis and Blastomyces dermatiditis, the production of GlcCer is mainly related to the yeast-pathogenic form, leading to the presence of antibodies to GlcCer in patient sera and suggesting its importance for fungal virulence [63,65,66]. In the plant pathogen Penicillium digitatum, knocking out the GlcCer synthase gene impairs its virulence in a citrus fruit infection model [67], suggesting that GlcCer plays an important role in virulence not only of mammal pathogens but also of plant pathogens.…”

“…It is composed of a future science group Review Rollin-Pinheiro, Singh, Barreto-Bergter & Del Poeta sphingoid base backbone linked to a fatty acid with a chain length ranging from 16 to 26 carbons via an amide bond, and to glucose via a β-glycosidic bond ( Figure 4B) [63]. The biosynthetic pathway from ceramide to the final GlcCer molecule includes ceramide C-8 desaturations (SLD8) and C-9 methylation (SMT1), and the transferring of the glucose moiety from UDP-glucose to ceramide by the GlcCer synthase (GCS1) [77].…”

“…Elucidation of the sphingolipid biosynthesis has been extremely important to understand the role of sphingolipids in fungal cells [63,75] and has also contributed to the discovery of inhibitors of the sphingolipid biosynthetic pathway. Along the biosynthetic pathway of sphingolipids, many inhibitors are known and some of them are related to antifungal activity (Figure 3) [90].…”

Sphingolipids from the human fungal pathogen Aspergillus fumigatus

“…In C. albicans, the presence of GlcCer and its methyl group are critical for the sensitivity to the plant defensin peptide AFP1 [30], showing the involvement of the methyl group in the interaction of GlcCer and the AFP1 defensin peptide. Interestingly, the loss of methyl group of GlcCer in C. neoformans induces an increase of membrane permeability and a defect in cell membrane organization in neutral/alkaline pH [29], suggesting that the methyl group of GlcCer is important to the interaction with other membrane components and to initiate the formation of lipid raft by tightening sphingolipids and ergosterol together [31].…”