Carnitine acetyltransferases are required for growth on non-fermentable carbon sources but not for pathogenesis in Candida albicans
| Autor: | Michael C. Lorenz, Huaijin Zhou |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Glyoxylate cycle
Hyphae Virulence Saccharomyces cerevisiae Microbiology Mice Gene Expression Regulation Fungal Candida albicans medicine Morphogenesis Animals Carnitine Sequence Deletion Carnitine O-Acetyltransferase biology Reverse Transcriptase Polymerase Chain Reaction Macrophages Genetic Complementation Test Peroxisome biology.organism_classification Corpus albicans Carbon Culture Media Up-Regulation Metabolic pathway Cytosol Biochemistry Female Metabolic Networks and Pathways medicine.drug |
| Zdroj: | Microbiology (Reading, England). 154(Pt 2) |
| ISSN: | 1350-0872 |
| Popis: | Carbon starvation is a significant stress encountered by the opportunistic fungal pathogen Candida albicans, and mutations in several pathways required to assimilate non-fermentable carbon sources attenuate virulence. These pathways -- beta-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 C. albicans, CTN1, CTN2 and CTN3. Strains lacking CTN1 or CTN2 were unable to grow on ethanol or acetate as sole carbon source; additionally, citrate was utilized poorly (Deltactn2) or not at all (Deltactn1) and the Deltactn2 mutant failed to grow on fatty acids as well. In contrast, deletion of CTN3 had no observable phenotype. All three genes were upregulated in the presence of non-fermentable carbon sources and after macrophage phagocytosis. CTN1 and CTN3 were able to complement the corresponding Saccharomyces cerevisiae Deltayat1 and Deltayat2 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 in vivo and in vitro and the contribution of metabolic pathways to virulence in C. albicans. |
| Databáze: | OpenAIRE |
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