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Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
Genetically Compromising Phospholipid Metabolism Limits Candida albicans' Virulence
Dorothy Wong1, James Plumb1, Hosamiddine Talab1
1Department of Natural Sciences, University of Michigan-Dearborn, 4901 Evergreen Rd., Dearborn, MI, 48128, USA.
Mycopathologia
|January 30, 2019
Summary
Altering phospholipid synthesis in Candida albicans by partially inhibiting key enzymes significantly reduces its virulence. This disruption affects cell membrane composition, offering a potential therapeutic target against fungal infections.
Area of Science:
- Mycology
- Molecular Biology
- Biochemistry
Background:
- Ergosterol synthesis inhibition is known to reduce Candida albicans virulence.
- The role of phospholipid synthesis and remodeling in C. albicans virulence is less understood.
- Investigating cell membrane composition offers potential new avenues for antifungal strategies.
Purpose of the Study:
- To test if limiting phospholipid synthesis or remodeling reduces C. albicans virulence.
- To generate and characterize C. albicans strains with partial inhibition of phospholipid synthesis genes.
- To evaluate the impact of altered phospholipid metabolism on fungal virulence.
Main Methods:
- Generated heterozygous deletion mutants for four key phospholipid synthesis/modification genes in C. albicans.
- Quantified gene transcript abundance using quantitative PCR.
- Assayed fungal virulence in a Caenorhabditis elegans host model.
- Analyzed phospholipid composition using electrospray ionization tandem mass spectrometry and principal component analysis.
Main Results:
- Partial inhibition of LRO1, CHO1, and LPT1 genes significantly reduced C. virulence by 23-38%.
- Restoring a functional allele reversed the virulence reduction in these mutants.
- Deletion heterozygotes showed significant alterations in phosphatidylinositol, lysophosphatidylcholine, and lysophosphatidylethanolamine levels.
- No growth or filamentation defects were observed in any mutant.
Conclusions:
- Partial inhibition of Lro1p, Cho1p, and Lpt1p effectively reduces C. albicans virulence.
- Altering phospholipid composition is a key mechanism underlying this virulence reduction.
- Pharmacological inhibition of these enzymes could be a viable strategy to combat C. albicans infections.
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