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Eukaryotic Cell doi:10.1128/EC.00017-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Carnitine-dependent transport of acetyl-CoA in Candida albicans is essential for growth on non-fermentable carbon sources and contributes to biofilm formation

Department of Medical Biochemistry and Genetic Metabolic Diseases, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands and Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, Aberdeen AB25 2ZD, United Kingdom and Department of Biomedical Engineering, University Medical Center Groningen and University of Groningen, P.O. Box 196, 9700 AD Groningen, The Netherlands

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

	Abstract

In eukaryotes, acetyl-CoA produced during peroxisomal fatty acid -oxidation needs to be transported to mitochondria for further metabolism. Two parallel pathways for acetyl-CoA transport have been identified in Saccharomyces cerevisiae, one being dependent on peroxisomal citrate synthase (Cit) while the other requires peroxisomal and mitochondrial carnitine acetyl-transferase (Cat) activity. Here we show that the human fungal pathogen Candida albicans lacks peroxisomal Cit, relying exclusively on Cat activity for transport of acetyl units. Deletion of the CAT2 gene encoding the major Cat in C. albicans resulted in a strain that had lost both peroxisomal and mitochondrial-associated Cat activity, could not grow on fatty acids or C2 carbon sources (acetate or ethanol), accumulated intracellular acetyl-CoA and showed strongly reduced fatty acid -oxidation activity. The cat2 null mutant was however not attenuated in virulence in a mouse model for systemic candidiasis. These observations support our previous results showing that peroxisomal fatty acid -oxidation activity is not essential for virulence of C. albicans. Biofilm formation by the cat2 mutant on glucose was slightly reduced compared to wild type, although both strains grew at the same rate on this carbon source. Our data show that C. albicans has diverged considerably from S. cerevisiae with respect to the mechanism of intracellular acetyl-CoA transport and imply that carnitine-dependence may be an important trait of this human fungal pathogen.