C. albicans assimilates carbon from sugars using the glycolytic pathway, and assimilates many non-fermentable carbon sources through the gluconeogenic pathway. The glyoxylate cycle allows C. albicans to assimilate two carbon compounds. Previous data have highlighted the importance of the glyoxylate cycle in invasive disease — this cycle is upregulated in C. albicans after exposure to phagocytes, and is required for fungal virulence. Nevertheless, the glyoxylate cycle is inhibited by concentrations of glucose similar to those found in the bloodstream of mammals, and so the role of the glyoxylate pathway in systemic candidiasis remains a puzzle.
To address this paradox, and to find out more about fungal metabolic strategies, the authors generated C. albicans strains that express green fluorescent protein (GFP) fusions to genes that encode key metabolic enzymes. Using these strains, they monitored the activity of these central carbon metabolic pathways in a range of systems, including a mouse model of systemic candidiasis. C. albicans upregulates the glyoxylate and gluconeogenic pathways during the early stages of systemic disease, after phagocytosis by neutrophils and macrophages. But in the later stages of infection, when C. albicans colonizes organs such as the kidney, the glycolytic pathway predominates. Mutations in each of these central metabolic pathways attenuate the virulence of C. albicans, indicating that all three are required for the establishment of a systemic infection.
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