Peroxisomal Fatty Acid β-Oxidation Is Not Essential for Virulence of Candida albicans
Open accessAbstract
Phagocytic cells form the first line of defense against infections by the human fungal pathogen Candida albicans. Recent in vitro gene expression data suggest that upon phagocytosis by macrophages, C. albicans reprograms its metabolism to convert fatty acids into glucose by inducing the enzymes of the glyoxylate cycle and fatty acid beta-oxidation pathway. Here, we asked whether fatty acid beta-oxidation, a metabolic pathway localized to peroxisomes, is essential for fungal virulence by constructing two C. albicans double deletion strains: a pex5Delta/pex5Delta mutant, which is disturbed in the import of most peroxisomal enzymes, and a fox2Delta/fox2Delta mutant, which lacks the second enzyme of the beta-oxidation pathway. Both mutant strains had strongly reduced beta-oxidation activity and, accordingly, were unable to grow on media with fatty acids as a sole carbon source. Surprisingly, only the fox2Delta/fox2Delta mutant, and not the pex5Delta/pex5Delta mutant, displayed strong growth defects on nonfermentable carbon sources other than fatty acids (e.g., acetate, ethanol, or lactate) and showed attenuated virulence in a mouse model for systemic candidiasis. The degree of virulence attenuation of the fox2Delta/fox2Delta mutant was comparable to that of the icl1Delta/icl1Delta mutant, which lacks a functional glyoxylate cycle and also fails to grow on nonfermentable carbon sources. Together, our data suggest that peroxisomal fatty acid beta-oxidation is not essential for virulence of C. albicans, implying that the attenuated virulence of the fox2Delta/fox2Delta mutant is largely due to a dysfunctional glyoxylate cycle.
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C. albicans FOX2, ICL1, and CAT2 mutants did not grow on oleic acid as a nutrient source.
“This correlates with past studies where a C. albicans FOX2 mutant (45), an ICL1 mutant (32), and a CAT2 mutant (46) did not grow on oleic acid as a nutrient source.”
From <i>Candida auris</i> metabolism and growth preferences in physiologically relevant skin-like conditions (2026) · cites this paper as [45]
It was postulated that acetyl-CoA feeding into the glyoxylate cycle might be derived from other non-fermentable carbon sources, such as lactate or acetate.
“Thereby, it was postulated that acetyl-CoA feeding into the glyoxylate cycle might be derived from other non-fermentable carbon sources, such as lactate or acetate (Piekarska et al., 2006; Ramirez and Lorenz, 2007).”
From Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate (2015) · cites this paper as Piekarska et al., 2006
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References 45 · Cited by 93
- Authors
- Piekarska, K., Mol, E., van den Berg, M., Hardy, G., van den Burg, J., van Roermund, C., MacCallum, D., Odds, F., & Distel, B.
- Affiliations
- Departments of Medical Biochemistry
- Genetic Metabolic Diseases, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands
- University of Aberdeen (GB)
- Corresponding author
- Distel, Ben
- Venue
- Eukaryotic Cell
- Publisher
- American Society for Microbiology
- Published
- 2006-11
- Volume
- 5
- Issue
- 11
- Pages
- 1847-1856
- ISSN
- 1535-9778 (ISSN-L)
- 1535-9786
- PMC
- PMC1694795
- OpenAlex
- W2132171565
- Cited by
- 93
- References
- 45
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 1 · 2017: 2 · 2016: 7 · 2015: 5 · 2014: 6 · 2013: 4 · 2012: 5
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Eukaryotic Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Funders
- Georgetown University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- Candida albicans, peroxisomal beta-oxidation, fungal virulence, glyoxylate cycle, PEX5, non-fermentable carbon sources, phagocytosis, macrophages, systemic candidiasis, fungal metabolism
- MeSH terms
- Animals, Candida albicans, Candidiasis, Enoyl-CoA Hydratase, Fatty Acids, Fungal Proteins, Humans, Oxidation-Reduction, 3-Hydroxyacyl CoA Dehydrogenases, Gene Targeting, Oleic Acid, Peroxisomes, Membrane Transport Proteins, Saccharomyces cerevisiae Proteins, Mice
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