Role of phospholipases in fungal fitness, pathogenicity, and drug development - lessons from cryptococcus neoformans
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Updated: May 31, 2026

Biolistic Transformation of a Fluorescent Tagged Gene into the Opportunistic Fungal Pathogen Cryptococcus neoformans
Published on: March 19, 2015
1Fungal Pathogenesis Laboratory, Centre for Infectious Diseases and Microbiology, Sydney Medical School-Western, Westmead Millennium Institute, University of Sydney at Westmead Hospital Westmead, NSW, Australia.
Abstract:
Many pathogenic microbes, including many fungi, produce phospholipases which facilitate survival of the pathogen in vivo, invasion and dissemination throughout the host, expression of virulence traits and evasion of host immune defense mechanisms. These phospholipases are either secreted or produced intracellularly and act by physically disrupting host membranes, and/or by affecting fungal cell signaling and production of immunomodulatory effectors. Many of the secreted phospholipases acquire a glycosylphosphatidylinositol sorting motif to facilitate membrane and/or cell wall association and secretion. This review focuses primarily on the role of two members of the phospholipase enzyme family, phospholipase B (Plb) and phosphatidylinositol (PI)-specific phospholipase C (PI-C/Plc), in fungal pathogenesis and in particular, what has been learnt about their function from studies performed in the model pathogenic yeast, Cryptococcus neoformans. These studies have revealed how Plb has adapted to become an important part of the virulence repertoire of pathogenic fungi and how its secretion is regulated. They have also provided valuable insight into how the intracellular enzyme, Plc1, contributes to fungal fitness and pathogenicity - via a putative role in signal transduction pathways that regulate the production of stress-protecting pigments, polysaccharide capsule, cell wall integrity, and adaptation to growth at host temperature. Finally, this review will address the role fungal phospholipases have played in the development of a new class of antifungal drugs, which mimic their phospholipid substrates.
Insights
Fungal phospholipases, like phospholipase B (Plb) and phosphatidylinositol-specific phospholipase C (PI-C/Plc), are crucial for pathogen survival and virulence. Studies in Cryptococcus neoformans reveal their roles in host invasion and immune evasion, informing new antifungal drug development.
Area of Science:
- Mycology
- Pathogenesis
- Enzymology
Background:
- Pathogenic fungi produce phospholipases that aid in host survival, invasion, and immune evasion.
- These enzymes disrupt host membranes and influence fungal cell signaling and virulence factor production.
- Secreted phospholipases often utilize glycosylphosphatidylinositol motifs for secretion and localization.
Purpose of the Study:
- To review the role of phospholipase B (Plb) and phosphatidylinositol (PI)-specific phospholipase C (PI-C/Plc) in fungal pathogenesis.
- To highlight insights gained from studying these enzymes in the model pathogen Cryptococcus neoformans.
- To discuss the implications of fungal phospholipases in the development of novel antifungal therapies.
Main Methods:
- Review of existing literature on fungal phospholipases, focusing on Plb and PI-C/Plc.
- Analysis of studies conducted in the pathogenic yeast Cryptococcus neoformans.
- Examination of the functional roles of Plb and Plc1 in fungal virulence and fitness.
Main Results:
- Plb is a key virulence factor in pathogenic fungi, with its secretion and regulation elucidated.
- Intracellular Plc1 contributes to fungal fitness and pathogenicity through signaling pathways.
- Plc1 influences pigment production, capsule formation, cell wall integrity, and thermotolerance.
Conclusions:
- Fungal phospholipases are essential virulence determinants, with Plb and Plc1 playing distinct but critical roles.
- Studies in Cryptococcus neoformans provide a model for understanding phospholipase function in fungal pathogenesis.
- Fungal phospholipases represent promising targets for the development of new antifungal drugs that mimic their substrates.
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