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Eukaryotic Cell, April 2008, p. 610-618, Vol. 7, No. 4
1535-9778/08/$08.00+0     doi:10.1128/EC.00017-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Carnitine-Dependent Transport of Acetyl Coenzyme A in Candida albicans Is Essential for Growth on Nonfermentable Carbon Sources and Contributes to Biofilm Formation

Departments of Medical Biochemistry,¹ Genetic Metabolic Diseases, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands,² Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, Aberdeen AB25 2ZD, United Kingdom,³ Department of Biomedical Engineering, University Medical Center Groningen and University of Groningen, P.O. Box 196, 9700 AD Groningen, The Netherlands⁴

Received 15 January 2008/ Accepted 7 February 2008

In eukaryotes, acetyl coenzyme A (acetyl-CoA) produced during peroxisomal fatty acid β-oxidation needs to be transported to mitochondria for further metabolism. Two parallel pathways for acetyl-CoA transport have been identified in Saccharomyces cerevisiae; one is dependent on peroxisomal citrate synthase (Cit), while the other requires peroxisomal and mitochondrial carnitine acetyltransferase (Cat) activities. 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 enzyme in C. albicans resulted in a strain that had lost both peroxisomal and mitochondrion-associated Cat activities, could not grow on fatty acids or C₂ carbon sources (acetate or ethanol), accumulated intracellular acetyl-CoA, and showed greatly reduced fatty acid β-oxidation activity. The cat2 null mutant was, however, not attenuated in virulence in a mouse model of systemic candidiasis. These observations support our previous results showing that peroxisomal fatty acid β-oxidation activity is not essential for C. albicans virulence. Biofilm formation by the cat2 mutant on glucose was slightly reduced compared to that by the 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.

Published ahead of print on 15 February 2008.