Peroxisomal fatty acid beta-oxidation is not essential for virulence of Candida albicans

Katarzyna Piekarska, Els Mol, Marlene van den Berg, Guy Hardy, Janny van den Burg, Carlo van Roermund, Donna Margaret MacCallum, Frank Odds, Ben Distel

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

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 P-oxidation pathway. Here, we asked whether fatty acid P-oxidation, a metabolic pathway localized to peroxisomes, is essential for fungal virulence by constructing two C. albicans double deletion strains: a pex5 Delta/pex5 Delta mutant, which is disturbed in the import of most peroxisomal enzymes, and a fox2 Delta/fox2 Delta 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 fox2 Delta/fox2 Delta mutant, and not the pex5 Delta/pex5 Delta 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 fox2 Delta/fox2 Delta mutant was comparable to that of the icl1 Delta/icl1 Delta 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 fox2 Delta/fox2 Delta mutant is largely due to a dysfunctional glyoxylate cycle.

Original languageEnglish
Pages (from-to)1847-1856
Number of pages10
JournalEukaryotic Cell
Volume5
Issue number11
DOIs
Publication statusPublished - Nov 2006

Keywords

  • yeast yarrowia lipolytica
  • Saccharomyces cerevisiae
  • glyoxylate cycle
  • isocitrate lyase
  • carnitine acetyltransferase
  • transcriptional response
  • membrane proteins
  • fungal pathogens
  • gene disruption
  • localization

Cite this

Piekarska, K., Mol, E., van den Berg, M., Hardy, G., van den Burg, J., van Roermund, C., ... Distel, B. (2006). Peroxisomal fatty acid beta-oxidation is not essential for virulence of Candida albicans. Eukaryotic Cell, 5(11), 1847-1856. https://doi.org/10.1128/EC.00093-06

Peroxisomal fatty acid beta-oxidation is not essential for virulence of Candida albicans. / Piekarska, Katarzyna; Mol, Els; van den Berg, Marlene; Hardy, Guy; van den Burg, Janny; van Roermund, Carlo; MacCallum, Donna Margaret; Odds, Frank; Distel, Ben.

In: Eukaryotic Cell, Vol. 5, No. 11, 11.2006, p. 1847-1856.

Research output: Contribution to journalArticle

Piekarska, K, Mol, E, van den Berg, M, Hardy, G, van den Burg, J, van Roermund, C, MacCallum, DM, Odds, F & Distel, B 2006, 'Peroxisomal fatty acid beta-oxidation is not essential for virulence of Candida albicans', Eukaryotic Cell, vol. 5, no. 11, pp. 1847-1856. https://doi.org/10.1128/EC.00093-06
Piekarska K, Mol E, van den Berg M, Hardy G, van den Burg J, van Roermund C et al. Peroxisomal fatty acid beta-oxidation is not essential for virulence of Candida albicans. Eukaryotic Cell. 2006 Nov;5(11):1847-1856. https://doi.org/10.1128/EC.00093-06
Piekarska, Katarzyna ; Mol, Els ; van den Berg, Marlene ; Hardy, Guy ; van den Burg, Janny ; van Roermund, Carlo ; MacCallum, Donna Margaret ; Odds, Frank ; Distel, Ben. / Peroxisomal fatty acid beta-oxidation is not essential for virulence of Candida albicans. In: Eukaryotic Cell. 2006 ; Vol. 5, No. 11. pp. 1847-1856.
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abstract = "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 P-oxidation pathway. Here, we asked whether fatty acid P-oxidation, a metabolic pathway localized to peroxisomes, is essential for fungal virulence by constructing two C. albicans double deletion strains: a pex5 Delta/pex5 Delta mutant, which is disturbed in the import of most peroxisomal enzymes, and a fox2 Delta/fox2 Delta 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 fox2 Delta/fox2 Delta mutant, and not the pex5 Delta/pex5 Delta 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 fox2 Delta/fox2 Delta mutant was comparable to that of the icl1 Delta/icl1 Delta 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 fox2 Delta/fox2 Delta mutant is largely due to a dysfunctional glyoxylate cycle.",
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AU - Hardy, Guy

AU - van den Burg, Janny

AU - van Roermund, Carlo

AU - MacCallum, Donna Margaret

AU - Odds, Frank

AU - Distel, Ben

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AB - 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 P-oxidation pathway. Here, we asked whether fatty acid P-oxidation, a metabolic pathway localized to peroxisomes, is essential for fungal virulence by constructing two C. albicans double deletion strains: a pex5 Delta/pex5 Delta mutant, which is disturbed in the import of most peroxisomal enzymes, and a fox2 Delta/fox2 Delta 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 fox2 Delta/fox2 Delta mutant, and not the pex5 Delta/pex5 Delta 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 fox2 Delta/fox2 Delta mutant was comparable to that of the icl1 Delta/icl1 Delta 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 fox2 Delta/fox2 Delta mutant is largely due to a dysfunctional glyoxylate cycle.

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KW - isocitrate lyase

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KW - transcriptional response

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KW - gene disruption

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