Phospholipid Dynamics in Fungal Pathogenesis

Phospholipids are fundamental constituents of fungal membranes, serving both structural and signalling roles that underpin each stage of infection. Dynamic remodelling of membrane composition enables pathogenic fungi to adapt to host environments, mediate hyphal growth, and resist immune defences. Biosynthetic pathways such as the CDP-diacylglycerol route and the Kennedy pathway interconnect to maintain supplies of phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC), while lipid-remodelling enzymes modulate membrane curvature and domain formation. Specific lipid species, notably phosphoinositides such as phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), act as localised signalling hubs to organise cytokinesis, cell-wall assembly and responses to antifungal agents. Alterations in phospholipid methylation and acylation pathways influence fungal morphology, biofilm formation and virulence traits, offering opportunities for therapeutic intervention. Recent advances in lipidomics, structural biology and high-throughput screening have illuminated enzyme mechanisms and lipid trafficking routes that are unique to fungi, highlighting candidate drug targets and strategies to overcome emerging resistance.

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Phospholipid Dynamics in Fungal Pathogenesis publication trend

The graph below shows the total number of articles in phospholipid dynamics in fungal pathogenesis across all publications each year (not limited to Nature Index journals).

Technical terms

Phosphatidylserine synthase (Cho1): Enzyme that catalyses the formation of phosphatidylserine from cytidyldiphosphate-diacylglycerol and serine, essential for membrane assembly.

Phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2): A phosphoinositide localised to the plasma membrane that regulates actin organisation, cytokinesis and antifungal responses.

Glycerophosphocholine acyltransferase (Gpc1): Enzyme initiating an alternative pathway of phosphatidylcholine biosynthesis by acylation of glycerophosphocholine.

Phospholipid methyltransferase (ChoC): Enzyme that methylates phospholipid head groups to interconvert PE and PC, influencing membrane fluidity and fungal virulence.

References

1. The small molecule CBR-5884 inhibits the Candida albicans phosphatidylserine synthase. mBio (2024).
2. Regulation of phosphatidylinositol-(4,5)-bisphosphate and active-Rho1p levels and distribution is crucial for correct spatio-temporal cytokinesis and echinocandin responses in Candida albicans. Antimicrobial Agents and Chemotherapy (2025).
3. The glycerophosphocholine acyltransferase Gpc1 contributes to phosphatidylcholine biosynthesis, long-term viability, and embedded hyphal growth in Candida albicans. Journal of Biological Chemistry (2023).
4. Functional, transcriptomic, and lipidomic studies of the choC gene encoding a phospholipid methyltransferase in Aspergillus fumigatus. Microbiology Spectrum (2023).