title: Carnitine-dependent transport of acetyl coenzyme A in Candida albicans is essential for growth on nonfermentable carbon sources and contributes to biofilm formation.
abstract: In eukaryotes, acetyl coenzyme A (acetyl-CoA) produced during peroxisomal fatty acid beta-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 C(2) carbon sources (acetate or ethanol), accumulated intracellular acetyl-CoA, and showed greatly reduced fatty acid beta-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 beta-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.
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Karin
authors.initials: K
authors.lastname: Strijbis
authors.forename: Carlo W T
authors.initials: CW
authors.lastname: van Roermund
authors.forename: Wouter F
authors.initials: WF
authors.lastname: Visser
authors.forename: Els C
authors.initials: EC
authors.lastname: Mol
authors.forename: Janny
authors.initials: J
authors.lastname: van den Burg
authors.forename: Donna M
authors.initials: DM
authors.lastname: MacCallum
authors.forename: Frank C
authors.initials: FC
authors.lastname: Odds
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Paramonova
authors.forename: Bastiaan P
authors.initials: BP
authors.lastname: Krom
authors.forename: Ben
authors.initials: B
authors.lastname: Distel
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D018441:Biofilms / Q000254:growth & development*; D001692:Biological Transport; D002176:Candida albicans / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D002177:Candidiasis / Q000382:microbiology; D002331:Carnitine / Q000378:metabolism*; D002332:Carnitine O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000201:enzymology; D009154:Mutation; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000201:enzymology; D014774:Virulence
chemical_list: D000105:Acetyl Coenzyme A; D002332:Carnitine O-Acetyltransferase; D002950:Citrate (si)-Synthase; D002331:Carnitine