1887

Abstract

Carbon starvation is a significant stress encountered by the opportunistic fungal pathogen , and mutations in several pathways required to assimilate non-fermentable carbon sources attenuate virulence. These pathways – -oxidation, the glyoxylate cycle and gluconeogenesis – are compartmentalized in the fungal cell between the peroxisome, mitochondria and cytosol; thus, the cell must transport key intermediates between these organelles. Transport of acetyl-CoA, a particularly important intermediate of carbon metabolism, is catalysed by membrane-associated carnitine acetyltransferases (CATs). We report here the characterization of the three predicted CAT genes in , and . Strains lacking or were unable to grow on ethanol or acetate as sole carbon source; additionally, citrate was utilized poorly (Δ) or not at all (Δ) and the Δ mutant failed to grow on fatty acids as well. In contrast, deletion of had no observable phenotype. All three genes were upregulated in the presence of non-fermentable carbon sources and after macrophage phagocytosis. and were able to complement the corresponding Δ and Δ mutants. However, these mutants had no obvious attenuation in virulence in a mouse model of disseminated candidiasis, in contrast to other carbon metabolism mutants. These findings extend our understanding of nutrient stress and and the contribution of metabolic pathways to virulence in .

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2008-02-01
2020-02-25
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