replicating inside macrophages utilise the glyoxylate cycle, presenting a highly selective target for the treatment of systemic candidiasis.
The fungus Candida albicans is found in the normal intestinal flora of mammals but is responsible for most of the fungal infections seen in immunocompromised patients. Candida is normally phagocytosed by macrophages and neutrophils and patients deficient in these immune cells are clearly highly susceptible to systemic candidiasis.
In the 5 July Nature Michael Lorenz & Gerald Fink at the Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, demonstrated that the glyoxylate cycle is required for fungal virulence, and suggested that this may be a novel target for chemotherapy.
They demonstrated that in C. albicans, phagocytosis leads to the upregulation of the glyoxalate cycle, as marked by the upregulation of the principal enzymes isocitrate lyase (ICL1) and malate synthase (MLS1). They infected mice with either wild type fungus or a strain lacking ICL1. Those injected with wild type fungus rapidly developed candidiasis and died after an average of...
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