Eukaryotic Cell
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EC Accepts, published online ahead of print on 8 September 2006
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Eukaryotic Cell doi:10.1128/EC.00093-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

PEROXISOMAL FATTY ACID {beta}-OXIDATION IS NOT ESSENTIAL FOR VIRULENCE OF C. ALBICANS

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

Depts. of Medical Biochemistry and Genetic Metabolic Diseases, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands; Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, Aberdeen AB25 2ZD, United Kingdom

* To whom correspondence should be addressed. Email: b.distel{at}amc.uva.nl.


  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 {beta}-oxidation pathway. Here, we asked the question 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 pex5{Delta}/{Delta} mutant, disturbed in the import of most peroxisomal enzymes, and a fox2{Delta}/{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}/{Delta} mutant, but not the pex5{Delta}/{Delta} mutant, displayed strong growth defects on non-fermentable 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}/{Delta} mutant was comparable to that of the icl1{Delta}/{Delta} mutant, which lacks a functional glyoxylate cycle and also fails to grow on non-fermentable 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}/{Delta} mutant is largely due to a dysfunctional glyoxylate cycle.




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