Lipid signalling in pathogenic fungi

Abstract

In recent years, the study of lipid signalling networks has significantly increased. Although best studied in mammalian cells, lipid signalling is now appreciated also in microbial cells, particularly in yeasts and moulds. For instance, microbial sphingolipids and their metabolizing enzymes play a key role in the regulation of fungal pathogenicity, especially in Cryptococcus neoformans, through the modulation of different microbial pathways and virulence factors. Another example is the quorum sensing molecule (QSM) farnesol. In fact, this QSM is involved not only in mycelial growth and biofilm formation of Candida albicans, but also in many stress related responses. In moulds, such as Aspergillus fumigatus, QSM and sphingolipids are important for maintaining cell wall integrity and virulence. Finally, fungal cells make oxylipins to increase their virulence attributes and to counteract the host immune defences. In this review, we discuss these aspects in details.

Fig. 1

Regulation of cryptococcal pathogenicity by the sphingolipid pathway. PI, phosphatidylinositol; Ipc1, inositol phosphoryl ceramide synthase; IPC, inositol phosphoryl ceramide; DAG, diacylglycerol; Pkc1, protein kinase C1; Lac1, laccase; Atf2, activating transcription factor 2; App1, antiphagocytic protein 1; Isc1, inositol phosphosphingolipid phospholipase C; IP, inositol phosphate; Pma1, plasma membrane ATPase 1; Gcs1, glucosylceramide synthase; UDP, uridine diphosphate; GlcCer, glucosylceramide. (A) Colonies of C. neoformans with wild-type (brown) and downregulated Ipc1 (white) grown on dopamine plates. (B) C. neoformans wild-type is about to be engulfed by a murine primary alveolar macrophages. White bar: 10 μm. (C) A J774.16 peritoneal macrophage containing several C. neoformans wild-type cells within its phagolysosome. White bar: 10 μm. (D) Mouse lung stained with mucicarmine shows several C. neoformans wild-type H99 cells in bronchioles. White bar: 5 μm.